Sample records for mdea methyldiethanolamine piperazine

  1. A study on equilibrium solubility for carbon dioxide in methyldiethanolamine-piperazine-water solution

    SciTech Connect

    Liu, H.B.; Zhang, C.F.; Xu, G.W.

    1999-10-01

    Activated methyldiethanolamine (MDEA) technology has been frequently applied for the removal of acidic gases such as CO{sub 2} and H{sub 2}S from gas streams. Solubilities of CO{sub 2} in aqueous mixtures of methyldiethanolamine (MDEA) and piperazine (PZ) have been measured for temperatures and CO{sub 2} partial pressures ranging from 30 to 90 C and 13.16 to 935.3 kPa, respectively. A modified Deshmukh-Mather thermodynamic model is used to correlate the experimental data with the average deviation of 9.8%, in which the effect of salts on Henry's constant is taken into consideration. The results also indicate that the second-order dissociation reaction for piperazine can be neglected. A simple model is also given with the average deviation of 11.6%.

  2. Aerobic biodegradability of methyldiethanolamine (MDEA) used in natural gas sweetening plants in batch tests and continuous flow experiments

    Microsoft Academic Search

    M. Fürhacker; A. Pressl; R. Allabashi

    2003-01-01

    Mixtures of different amines including tertiary amines (methyldiethanolamine, MDEA) are commonly used for the removal of CO2 from gas mixtures or in gas sweetening processes for the extraction of CO2 and H2S. The absorber solutions used can be released into the industrial waste water due to continuous substitution of degraded MDEA, periodically cleaning processes or an accidental spill. In this

  3. Equilibrium solubilities of CO/sub 2/ and H/sub 2/S in diethanolamine (DEA) and methyldiethanolamine (MDEA) solutions

    SciTech Connect

    Ho, A.S.; Equren, P.R. (Amoco Production Co., Tulsa, OK (US))

    1988-01-01

    The ability to predict equilibrium phase behavior in systems containing CO/sub 2/ and/or H/sub 2/S in alkanolamine solutions such as diethanolamine (DEA) and methyldiethanolamine (MDEA) is of vital importance for proper design and operation of acid gases treating systems. Literature data for the solubilities of CO/sub 2/ and/or H/sub 2/S in DEA and MDEA systems have been compiled and evaluated. Experimental measurements have also been made to confirm literature data and to expand the data base. A vapor-liquid equilibrium (VLE) model similar to the one developed by Kent and Eisenberg has been developed to correlate the data. The model gives the most accurate predictions when compared to other VLE models available for predicting equilibrium acid gas partial pressures over DEA and MDEA solutions.

  4. Thermodynamics of Piperazine/Methyldiethanolamine/Water/Carbon Sanjay Bishnoi and Gary T. Rochelle*

    E-print Network

    Rochelle, Gary T.

    predicts PZ losses of the same magnitude as MDEA in a blend indicative of industrial concentrations, even systems are cru- cial to understanding their industrial use to remove acid gas from process gas streams, is the major reason PZ blends have a higher mass-transfer capability than many other blends studied

  5. Heat capacity of aqueous monoethanolamine, diethanolamine, N-methyldiethanolamine, and N-methyldiethanolamine-based blends with carbon dioxide

    SciTech Connect

    Weiland, R.H.; Dingman, J.C.; Cronin, D.B. [Optimized Gas Treating, Inc., Houston, TX (United States)] [Optimized Gas Treating, Inc., Houston, TX (United States)

    1997-09-01

    New data are reported on the heat capacity of CO{sub 2}-loaded, aqueous solutions of monoethanolamine (MEA), diethanolamine (DEA), N-methyldiethanolamine (MDEA), and aqueous MDEA-based blends with MEA and DEA. The work reported here was motivated by the need to quantify the effect of acid gas loading on the important physical properties of gas-sweetening solvents.

  6. Diffusivity of nitrous oxide in N-methyldiethanolamine + diethanolamine + water

    SciTech Connect

    Rinker, E.B.; Russell, J.W.; Tamimi, A.; Sandall, O.C. [Univ. of California, Santa Barbara, CA (United States). Dept. of Chemical Engineering

    1995-05-01

    The tertiary amine N-methyldiethanolamine and the secondary amine diethanolamine are commonly used in the gas-treating industry as chemical solvents for the removal of acid gases such as CO{sub 2} and H{sub 2}S. The diffusion coefficients for nitrous oxide in aqueous solutions consisting of N-methyldiethanolamine (MDEA) and diethanolamine (DEA) were measured over the temperature range 293--353 K for a total amine concentration of 50 mass % and for the mass ratio of DEA to MDEA varying from 0.0441 to 0.588. The experimental diffusion coefficients were found to be relatively insensitive to the mass ratio of amines.

  7. Viscosity of aqueous solutions of n-methyldiethanolamine and of diethanolamine

    SciTech Connect

    Teng, T.T.; Maham, Y.; Hepler, L.G.; Mather, A.E. (Univ. of Alberta, Edmonton, Alberta (Canada))

    1994-04-01

    Aqueous solutions of alkanolamines such as monoethanolamine (MEA), diethanolamine (DEA), N-methyldiethanolamine (MDEA), di-2-propanolamine (DIPA), and bis[2-(hydroxyamino)ethyl] ether (DGA) are good solvents for the removal of acid gases such as CO[sub 2] and H[sub 2]S from the gas streams of many processes in the natural gas, petroleum, ammonia synthesis, and some chemical industries. The viscosity of aqueous solutions of methyldiethanolamine (MDEA) and of diethanolamine (DEA) have been measured at five temperatures in the range 25--80 C throughout the whole concentration range. The viscosity has been correlated as a function of composition for use in industrial calculations.

  8. Diffusivity of nitrous oxide in aqueous solutions of N-methyldiethanolamine and diethanolamine from 293 to 368 K

    SciTech Connect

    Tamimi, A.; Rinker, E.B.; Sandall, O.C. (Univ. of California, Santa Barbara, CA (United States). Dept. of Chemical and Nuclear Engineering)

    1994-04-01

    The diffusion coefficients for nitrous oxide in aqueous solutions of diethanolamine (DEA) and N-methyldiethanolamine (MDEA) were determined using a wetted-sphere absorber over the temperature range 293--368 K. The ranges of amine concentrations covered in the experiments were 10--30 mass % for DEA and 10--50 mass % for MDEA. The diffusion coefficients indicated a linear dependence on amine concentration, but the temperature dependence was nonlinear. It was found that the diffusivity of N[sub 2]O in aqueous DEA is always less than that in aqueous MDEA under equivalent conditions of amine concentration and temperature.

  9. Series of isostructural planar lanthanide complexes [Ln(III)4(mu3-OH)2(mdeaH)2(piv)8] with single molecule magnet behavior for the Dy4 analogue.

    PubMed

    Abbas, Ghulam; Lan, Yanhua; Kostakis, George E; Wernsdorfer, Wolfgang; Anson, Christopher E; Powell, Annie K

    2010-09-01

    A series of five isostructural tetranuclear lanthanide complexes of formula [Ln(4)(mu(3)-OH)(2)(mdeaH)(2)(piv)(8)], (mdeaH(2) = N-methyldiethanolamine; piv = pivalate; Ln = Tb (1), Dy (2), Ho (3), Er (4), and Tm (5)) have been synthesized and characterized. These clusters have a planar "butterfly" Ln(4) core. Magnetically, the Ln(III) ions are weakly coupled in all cases; the Dy(4) compound 2 shows Single Molecule Magnet (SMM) behavior. PMID:20704320

  10. Modeling CO{sub 2} and H{sub 2}S solubility in MDEA and DEA: Design implications

    SciTech Connect

    Rochelle, G.T.; Posey, M. [Univ. of Texas, Austin, TX (United States)

    1996-12-31

    The solubility of H{sub 2}S and CO{sub 2} in aqueous alkanolamines affects solution capacity and the required circulation rate for acid gas absorption. These thermodynamics also determine the relationship of steam rate and the lean loading of the solution which in turn sets the leak of acid gas from the top of the absorber. Finally, the mechanisms of mass transfer and the role of kinetics, especially in stripping, depend on the vapor/liquid equilibria. Published measurements of CO{sub 2} and H{sub 2}S solubility in methyldiethanolamine (MDEA) and diethanolamine (DEA) are not in general agreement, especially at low loading of acid gas. The available sets of solubility data have been regressed with the AspenPlus electrolyte/NRTL model. All of the parameters and constants that make up this model have been carefully evaluated. Independent thermodynamic data such as freezing point and heat of mixing have been included in the regression to strengthen the estimates of model parameters. The parameters for each set of solubility data have been evaluated in an attempt to determine which set is correct. Each evaluated model has been used to calculate the acid gas capacity and minimum stripping steam rate for several industrial cases of acid gas absorption/stripping.

  11. Converting to DEA/MDEA mix ups sweetening capacity

    SciTech Connect

    Spears, M.L. [Union Pacific Resources, Bryan, TX (United States); Hagan, K.M. [Union Pacific Resources, Ft. Worth, TX (United States); Bullin, J.A.; Michalik, C.J. [Bryan Research and Engineering, Bryan, TX (United States)

    1996-08-12

    Mixing amines can be the best method for increasing capacity or improving efficiency in an amine sweetening unit. In many cases, it may be possible simply to add a second amine to the existing solution on the fly, or as the unit is running. Union Pacific Resources` Bryan, Tex., gas plant provides one example. The plant was converted from diethanolamine (DEA) to a DEA/MDEA (methyl DEA) mixture after analysis by TSWEET, a process-simulation program. After conversion, CO{sub 2} levels in the sales gas fell to less than pipeline specifications. Data were taken for the absorber at a constant amine circulation of 120 gpm. A comparison of the performance data to the values calculated by the program proved the accuracy of TSWEET. The conversion and performance of the plant are described.

  12. Determination of rate constants for the reaction between methyldiethanolamine and carbon dioxide

    E-print Network

    Brabson, Charles Meade

    1985-01-01

    DETERMINATION OF RATE CONSTANTS FOR THE REACTION BETWEEN METHYLDIETHANOLAMINE AND CARBON DIOXIDE A Thesis by CHARLES MEADE BRABSON, JR. Submitted to the Graduate College of Texas A6M University in partial fulfillment of the requirements... for the degree of MASTER OF SCIENCE August 1985 Major Subject: Chemical Engineering DETERMINATION OF RATE CONSTANTS FOR THE REACTION BETWEEN METHYLDIETHANOLAMINE AND CARBON DIOXIDE A Thesis by CHARLES MEADE BRABSONp JR. Approved as to style and content...

  13. Piperazine-induced occupational asthma

    SciTech Connect

    Hagmar, L.; Bellander, T.; Bergoeoe, B.; Simonsson, B.G.

    1982-03-01

    Asthmatic reactions were studied among some 130 factory workers who handled amines and other chemicals. Among present employees, we found 15 cases of asthma associated with occupational exposure to chemicals; among former employees there were at least 18. The inducing agent was judged to be piperazine in 29 persons and ethylenediamine (EDA) in three. The asthma was of the late or dual type; immediate reactions alone were to seen. No one had attacks of asthma before employment, and atopic subjects were not preferentially affected. Routine spirometry revealed airway obstruction in fewer than half of the recent cases. Tests of nonspecific bronchial reactivity with methacholine in six subjects with recent asthma showed hyperactivity in five, while tow subjects with earlier asthma did not have hyperactivity. Bronchial provocation tests with piperazine in one subject were positive both in the factory and in the laboratory. The level of piperazine was 1.2 mg/m3 time-weighted average (TWA) in a work place associated with induction of the asthmatic state, and 0.3 mg/m3 in a place connected with attacks in ''sensitized'' subjects.

  14. Towards an implantable biochip for glucose and lactate monitoring using microdisc electrode arrays (MDEAs).

    PubMed

    Abdur Rahman, Abdur Rub; Justin, Gusphyl; Guiseppi-Elie, Anthony

    2009-02-01

    A complete electrochemical cell-on-a-chip that uses the MicroDisc Electrode Array (MDEA) working electrode (WE) design was evaluated for eventual intramuscular implantation for the continuous amperometric monitoring of glucose and lactate in an animal trauma model. The microfabricated ECC MDEA5037 comprises two discrete electrochemical cells-on-a-chip (ECCs), each with a reference, counter, and MDEA working electrode. Each MDEA comprises 37 microdiscs (diameter = 50 microm) arranged in a Hexagonal Closed Packed (HCP) arrangement with a center to center distance (d) of 100 microm. Cyclic Voltammetry (CV) and Electrical Impendence Spectroscopy (EIS) reveals that this device scales in its interfacial properties with a corresponding MDEA 050 device that comprises 5,184 microdiscs. Parallel development of miniaturized mixed-signal integrated electronics for wireless reprogramming, data acquisition and communication addresses the key issues involved in developing measurement electronics, AD/DA processing, power management and telemetry for implantable amperometric biosensors. A generalized electronics platform based on the Texas Instruments TI NC01101 chip has been developed that may be readily applied to many types of biotransducers with minor modifications. PMID:18677565

  15. The effect of phosphoric acid on the absorption of carbon dioxide into solutions of methyldiethanolamine

    E-print Network

    Cordi, Eric Marshall

    1991-01-01

    of carbon dioxide in these solutions was slower than predicted, given the amount of free MDEA present. The reduced values of the pseudo-first-order rate constant were tested statistically to cone!ate the rate depression with free MDEA and hydrogen...-away view) . . Page 21 22 4. Two-Film Model of Mass Transfer. . . 32 5. Comparative Arrhenius Plot of Significant CO&/MDEA Research. 6. Pseudo-first-order Rate Constants at 25'C 51 68 7. Free Amine Plot for Pseudo-first-order Rate Constants 69 8...

  16. The effect of phosphoric acid on the absorption of carbon dioxide into solutions of methyldiethanolamine 

    E-print Network

    Cordi, Eric Marshall

    1991-01-01

    used for this project was generously donated by Texaco Chemical Company. TABLE OF CONTENTS CHAFER Page I INTRODUCTION II LITERATURE REVIEW Gas Sweetening Technology. Physical Pmperties of MDEA, Chemical Reactions in the MDEA Process... containing acidic impurities, such as carbon dioxide (COz) and hydrogen sulfide (HzS), has continued to evolve over several decades. R. R. Bottoms obtained the first patent in 1930 for the treatment of natural gas with a liquid alkanolamine solution. Since...

  17. Piperazine pivoted transition metal dithiocarbamates

    NASA Astrophysics Data System (ADS)

    Khan, Sadaf; Nami, Shahab A. A.; Siddiqi, K. S.

    2008-03-01

    A quadridentate ligand disodium bis(2,2'-dithiopiperazinato-2,2'-diamino diethylamine) Na 2L 2 and its self assembled transition metal complexes of the type, M 2(L 2) 2 {M = Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II)} have been reported. The piperazine pivoted homodinuclear complexes have been characterized by a range of spectral, thermal, microanalytical and conductometric techniques. On the basis of IR and 1HNMR data a symmetrical bidentate coordination of the dithiocarbamato moiety has been observed in all the cases. The TGA profile of the ligand exhibits two stage thermolytic pattern although the complexes decompose in three steps, respectively. Metal sulfide is found to be the end product. The formation of homodinuclear complexes has been ascertained on the basis of FAB mass spectral data and a probable fragmentation pattern has been proposed. On the basis of UV-visible spectroscopic results and room temperature magnetic moment data a tetrahedral geometry has been proposed for all the complexes except for the Ni(II) and Cu(II) which are found to be square-planar.

  18. Piperazine-based nucleic acid analogs

    DOEpatents

    Schmidt, Jurgen; Silks, Louis A.; Michalczyk, Ryszard

    2005-01-11

    A novel nucleoside analog is disclosed which comprises a piperazine ring in the place of the ring ribose or deoxyribose sugar. Monomers utilizing a broad variety of nucleobases are disclosed, as well as oligomers comprising the monomers disclosed herein linked by a variety of linkages, including amide, phosphonamide, and sulfonamide linkages. A method of synthesizing the nucleoside analogs is also disclosed.

  19. 21 CFR 520.1802a - Piperazine-carbon disulfide complex suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 2013-04-01 false Piperazine-carbon disulfide complex suspension. 520...ANIMAL DRUGS § 520.1802a Piperazine-carbon disulfide complex suspension. (a...suspension contains 7.5 grams of piperazine-carbon disulfide complex. The...

  20. 21 CFR 520.1802a - Piperazine-carbon disulfide complex suspension.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 2014-04-01 false Piperazine-carbon disulfide complex suspension. 520...ANIMAL DRUGS § 520.1802a Piperazine-carbon disulfide complex suspension. (a...suspension contains 7.5 grams of piperazine-carbon disulfide complex. The...

  1. Gene cloning and characterization of MdeA, a novel multidrug efflux pump in Streptococcus mutans.

    PubMed

    Kim, Do Kyun; Kim, Kyoung Hoon; Cho, Eun Ji; Joo, Seoung-Je; Chung, Jung-Min; Son, Byoung Yil; Yum, Jong Hwa; Kim, Young-Man; Kwon, Hyun-Ju; Kim, Byung-Woo; Kim, Tae Hoon; Lee, Eun-Woo

    2013-03-01

    Multidrug resistance, especially multidrug efflux mechanisms that extrude structurally unrelated cytotoxic compounds from the cell by multidrug transporters, is a serious problem and one of the main reasons for the failure of therapeutic treatment of infections by pathogenic microorganisms as well as of cancer cells. Streptococcus mutans is considered one of the primary causative agents of dental caries and periodontal disease, which comprise the most common oral diseases. A fragment of chromosomal DNA from S. mutans KCTC3065 was cloned using Escherichia coli KAM32 as host cells lacking major multidrug efflux pumps. Although E. coli KAM32 cells were very sensitive to many antimicrobial agents, the transformed cells harboring a recombinant plasmid became resistant to several structurally unrelated antimicrobial agents such as tetracycline, kanamycin, rhodamin 6G, ampicillin, acriflavine, ethidium bromide, and tetraphenylphosphonium chloride. This suggested that the cloned DNA fragment carries a gene encoding a multidrug efflux pump. Among 49 of the multidrug-resistant transformants, we report the functional gene cloning and characterization of the function of one multidrug efflux pump, namely MdeA from S. mutans, which was expressed in E. coli KAM32. Judging from the structural and biochemical properties, we concluded that MdeA is the first cloned and characterized multidrug efflux pump using the proton motive force as the energy for efflux drugs. PMID:23462018

  2. CO/sub 2/ desorption from DEA and DEA-promoted MDEA

    SciTech Connect

    Critchfield, J.E.; Rochelle, G.T. (Dept. of Chemical Engineering, The Univ. of Texas at Austin (US))

    1988-01-01

    CO/sub 2/ desorption rates were measured in 2 M diethanolamine and 2 M diethanolamine-promoted methyldiethanolamine solutions at 25{sup 0}C. CO/sub 2/ vapor pressure equilibria were estimated through extrapolation of the measured rates. The estimated vapor pressures were used to calculate apparent rate constants, and the resulting rate constants were interpreted as a function of CO/sub 2/ loading. The rate constants derived from the low driving force desorption experiments were compared with values obtained from high driving force, irreversible absorption experiments. In the absorption work, the effect of varied driving force on the resulting apparent rate constant was studied. The experimental results confirm that the absorption experiments were not affected by diffusion constraints. The agreement between the apparent rate constants determined from the absorption and desorption techniques was found to be very good.

  3. Kinetics of absorption of COâ in concentrated aqueous methyldiethanolamine solutions in the range 296 K to 343 K

    Microsoft Academic Search

    Fatos Pani; Alain Gaunand; Renaud Cadours; Chakib Bouallou; Dominique Richon

    1997-01-01

    The kinetics of COâ absorption by aqueous solutions of methyl diethanol amine (MDEA) were measured in the temperature range (296--343) K and MDEA concentration range (830--4,380) mol\\/m³ (10--50 mass %). A thermoregulated constant interfacial area Lewis-type cell was operated by recording the pressure drop during batch absorption. The kinetic results are in agreement with a fast regime of absorption according

  4. Carbon dioxide capture with concentrated, aqueous piperazine

    Microsoft Academic Search

    Stephanie A. Freeman; Ross Dugas; David H. Van Wagener; Thu Nguyen; Gary T. Rochelle

    2010-01-01

    Concentrated, aqueous piperazine (PZ) has been investigated as a novel amine solvent for carbon dioxide (CO2) absorption. The CO2 absorption rate of aqueous PZ is more than double that of 7m MEA and the amine volatility at 40°C ranges from 11 to 21ppm. Thermal degradation is negligible in concentrated, aqueous PZ up to a temperature of 150°C, a significant advantage

  5. The degradation mechanism of wastewater containing MDEA using UV\\/H2O2 advanced oxidation process

    Microsoft Academic Search

    Sabtanti Harimurti; Abul Aziz Omar; Anisa Ur Rahmah; Thanpalan Murugesan

    2011-01-01

    Alkanolamines such as MEA, DEA, MDEA and DIPA in aqueous solutions is frequently used for scrubbing carbon dioxide from natural gas. High quantity of alkanolamine appears in the wastewater during cleaning and maintenance as well as shutdown of the absorption and desorption columns. The alkanolamines waste is toxic to the environment and this wastewater cannot be treated in the conventional

  6. Complexation of metals with piperazine-containing azamacrocyclic fluorophores.

    PubMed

    Angelovski, Goran; Costisella, Burkhard; Kolari?, Branko; Engelhard, Martin; Eilbracht, Peter

    2004-08-01

    Azamacrocyclic fluorophores containing piperazine units were synthesized using sequential rhodium-catalyzed regioselective hydroformylation-reductive amination. A piperazine unit is introduced into the macrocycles to act simultaneously as electron donor and binding site. The macrocycles chelate divalent cations, either Zn2+ or Co2+, which considerably enhanced fluorescence. Complexation with Zn2+ was additionally confirmed by NMR. PMID:15287772

  7. Action of Piperazine on the Neuromuscular System of Ascaris lumbricoides

    Microsoft Academic Search

    J. Del Castillo; T. A. Morales; V. Sanchez

    1963-01-01

    PIPERAZINE is the drug most commonly used for the treatment of ascariasis, in preference to other anthelmintics, because it produces a flaccid paralysis of the parasites1 rather than hyperactivity. Though no direct evidence was available, it was suggested that such paralysis might be due to a curare-like effect, since piperazine prevents the stimulating action of acetylcholine on Ascaris muscle2.

  8. Contribution of artifacts to N-methylated piperazine cyanide adduct formation in vitro from N-alkyl piperazine analogs.

    PubMed

    Zhang, Minli; Resuello, Christina M; Guo, Jian; Powell, Mark E; Elmore, Charles S; Hu, Jun; Vishwanathan, Karthick

    2013-05-01

    In the liver microsome cyanide (CN)-trapping assays, piperazine-containing compounds formed significant N-methyl piperazine CN adducts. Two pathways for the N-methyl piperazine CN adduct formation were proposed: 1) The ?-carbon in the N-methyl piperazine is oxidized to form a reactive iminium ion that can react with cyanide ion; 2) N-dealkylation occurs followed by condensation with formaldehyde and dehydration to produce N-methylenepiperazine iminium ion, which then reacts with cyanide ion to form the N-methyl CN adduct. The CN adduct from the second pathway was believed to be an artifact or metabonate. In the present study, a group of 4'-N-alkyl piperazines and 4'-N-[¹³C]methyl-labeled piperazines were used to determine which pathway was predominant. Following microsomal incubations in the presence of cyanide ions, a significant percentage of 4'-N-[¹³C]methyl group in the CN adduct was replaced by an unlabeled natural methyl group, suggesting that the second pathway was predominant. For 4'-N-alkyl piperazine, the level of 4'-N-methyl piperazine CN adduct formation was limited by the extent of prior 4'-N-dealkylation. In a separate study, when 4'-NH-piperaziens were incubated with potassium cyanide and [¹³C]-labeled formaldehyde, 4'-N-[¹³C]methyl piperazine CN-adduct was formed without NADPH or liver microsome suggesting a direct Mannich reaction is involved. However, when [¹³C]-labeled methanol or potassium carbonate was used as the one-carbon donor, 4'-N-[¹³C]methyl piperazine CN adduct was not detected without liver microsome or NADPH present. The biologic and toxicological implications of bioactivation via the second pathway necessitate further investigation because these one-carbon donors for the formation of reactive iminium ions could be endogenous and readily available in vivo. PMID:23431111

  9. Correlation and prediction of the solubility of CO{sub 2} and H{sub 2}S in an aqueous solution of methyldiethanolamine and sulfolane

    SciTech Connect

    Qian, W.M.; Li, Y.G. [Tsinghua Univ., Beijing (China). Dept. of Chemical Engineering; Mather, A.E. [Univ. of Alberta, Edmonton, Alberta (Canada). Dept. of Chemical Engineering

    1995-07-01

    The Clegg-Pitzer equations with some simplifications are used to correlate the vapor-liquid equilibrium data for the CO{sub 2}-methyldiethanolamine-sulfolane-H{sub 2}O and H{sub 2}S-methyldiethanolamine-sulfolane-H{sub 2}O systems. The interaction parameters determined from data for the binary, ternary, and quaternary systems can be used to predict the quinary mixed solvent systems without any additional parameters. The model is applied to the CO{sub 2}-H{sub 2}S-methyldiethanolamine-sulfolane-H{sub 2}O system containing three neutral solvents (methyldiethanolamine, sulfolane, and H{sub 2}O), two neutral solutes (CO{sub 2} and H{sub 2}S), and three ionic species (MDEAH{sup +}, HCO{sub 3}{sup {minus}}, and HS{sup {minus}}) with three main chemical equilibria simultaneously involved.

  10. Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process.

    PubMed

    Salata, Cristiano; Baritussio, Aldo; Munegato, Denis; Calistri, Arianna; Ha, Huy Riem; Bigler, Laurent; Fabris, Fabrizio; Parolin, Cristina; Palù, Giorgio; Mirazimi, Ali

    2015-07-01

    Ebola virus disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and a treatment has not been developed yet. Recently, it has been shown that cationic amphiphiles, among them the antiarrhythmic drug amiodarone, inhibit filovirus infection. In the present work, we investigated how amiodarone interferes with Ebola virus infection. Wild-type Sudan ebolavirus and recombinant vesicular stomatitis virus, pseudotyped with the Zaire ebolavirus glycoprotein, were used to gain further insight into the ability of amiodarone to affect Ebola virus infection. We show that amiodarone decreases Ebola virus infection at concentrations close to those found in the sera of patients treated for arrhythmias. The drug acts by interfering with the fusion of the viral envelope with the endosomal membrane. We also show that MDEA, the main amiodarone metabolite, contributes to the antiviral activity. Finally, studies with amiodarone analogues indicate that the antiviral activity is correlated with drug ability to accumulate into and interfere with the endocytic pathway. Considering that it is well tolerated, especially in the acute setting, amiodarone appears to deserve consideration for clinical use in EVD. PMID:25933611

  11. 40 CFR 721.10047 - Polyphosphoric acids, compds. with piperazine.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...1) The chemical substance identified as a polyphosphoric acids, compds. with piperazine (PMN P-02-766; CAS No. 383905-85-9) is subject to reporting under this section for the significant new uses described in paragraph (a)(2)...

  12. 40 CFR 721.10047 - Polyphosphoric acids, compds. with piperazine.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...1) The chemical substance identified as a polyphosphoric acids, compds. with piperazine (PMN P-02-766; CAS No. 383905-85-9) is subject to reporting under this section for the significant new uses described in paragraph (a)(2)...

  13. 40 CFR 721.10047 - Polyphosphoric acids, compds. with piperazine.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...1) The chemical substance identified as a polyphosphoric acids, compds. with piperazine (PMN P-02-766; CAS No. 383905-85-9) is subject to reporting under this section for the significant new uses described in paragraph (a)(2)...

  14. 40 CFR 721.10047 - Polyphosphoric acids, compds. with piperazine.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...1) The chemical substance identified as a polyphosphoric acids, compds. with piperazine (PMN P-02-766; CAS No. 383905-85-9) is subject to reporting under this section for the significant new uses described in paragraph (a)(2)...

  15. 40 CFR 721.10047 - Polyphosphoric acids, compds. with piperazine.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...1) The chemical substance identified as a polyphosphoric acids, compds. with piperazine (PMN P-02-766; CAS No. 383905-85-9) is subject to reporting under this section for the significant new uses described in paragraph (a)(2)...

  16. Kinetics of absorption of CO{sub 2} in concentrated aqueous methyldiethanolamine solutions in the range 296 K to 343 K

    SciTech Connect

    Pani, F.; Gaunand, A.; Cadours, R.; Bouallou, C.; Richon, D. [Ecole Nationale Superieure des Mines de Paris (France). Centre de Recherche en Procedes de Transformation de la Matiere] [Ecole Nationale Superieure des Mines de Paris (France). Centre de Recherche en Procedes de Transformation de la Matiere

    1997-03-01

    The kinetics of CO{sub 2} absorption by aqueous solutions of methyl diethanol amine (MDEA) were measured in the temperature range (296--343) K and MDEA concentration range (830--4,380) mol/m{sup 3} (10--50 mass %). A thermoregulated constant interfacial area Lewis-type cell was operated by recording the pressure drop during batch absorption. The kinetic results are in agreement with a fast regime of absorption according to film theory. MDEA depletion at the interface has a significant effect on the kinetics at the CO{sub 2} pressures (100 to 200 kPa) studied in this work, especially at low temperatures and low MDEA concentrations. Considering only the reaction between CO{sub 2} and MDEA, the CO{sub 2} absorption appears as a first-order reaction with respect to MDEA. The activation energy found for the reaction between CO{sub 2} and MDEA is 45 kJ/mol, but this value depends significantly (by about 10% in the worst case) on the vapor-liquid equilibrium data used.

  17. 21 CFR 520.1805 - Piperazine phosphate with thenium closylate tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...Piperazine phosphate with thenium closylate tablets. 520.1805 Section 520.1805 Food...Piperazine phosphate with thenium closylate tablets. (a) Specifications. Each scored tablet contains the equivalent of 250...

  18. Degradation of piperazine by Paracoccus sp. TOH isolated from activated sludge.

    PubMed

    Cai, Shu; Li, Xin; Cai, Tianming; He, Jian

    2013-02-01

    Piperazine is widely used as an intermediate in the manufacture of insecticides, rubber chemicals, corrosion inhibitors, and urethane. In this study, a highly effective piperazine-degrading bacteria strain, TOH, was isolated from the acclimated activated sludge of a pharmaceutical plant. This strain, identified as Paracoccus sp., utilises piperazine as the sole source of carbon, nitrogen and energy for growth. The optimal pH and temperature for the growth of TOH were 8.0 and 30°C, respectively. The effects of co-substrates and heavy metals on the degradation efficiency of piperazine were investigated. The results indicated that exogenously supplied glucose promoted the degradation of piperazine, while the addition of ammonium chloride slightly inhibited piperazine degradation. Metal ions such as Ni(2+) and Cd(2+) inhibited the degradation of piperazine, whereas Mg(2+) increased it. In addition, metabolic intermediates were identified by mass spectrometry, allowing a degradation pathway for piperazine to be proposed for the first time. PMID:23334008

  19. Pilot plant for CO2 capture with aqueous piperazine/potassium carbonate , Gary T. Rochelle1

    E-print Network

    Rochelle, Gary T.

    GHGT-8 1 Pilot plant for CO2 capture with aqueous piperazine/potassium carbonate Eric Chen1 , Gary pilot for CO2 capture was successfully operated using potassium carbonate promoted with piperazine, potassium carbonate, piperazine Introduction Several amine-promoted potassium carbonate solvents have been

  20. The Piperazine Space in Isocyanide-based MCR Chemistry

    NASA Astrophysics Data System (ADS)

    Huang, Yijun; Khoury, Kareem; Dömling, Alexander

    Piperazines and its congeners, (di)keto piperazines are valuable tools in drug discovery, providing a natural path for the process peptide > peptidomimetic > small molecule also called depeptisation. Moreover, they can provide molecular probes to understand molecular pathways for diseases of unmet medical need. However, in order to better understand the design of such value added compounds, the detailed understanding of scope and limitation of their synthesis as well as their 3D structures and associated physicochemical properties is indispensables. Isocyanide multicomponent reaction (MCR) chemistry provides a prime tool for entering the chemical space of (di)(keto)piperazines since not less then 20 different ways exist to access a diversity of related scaffolds.

  1. Piperazine oxadiazole inhibitors of acetyl-CoA carboxylase.

    PubMed

    Bourbeau, Matthew P; Siegmund, Aaron; Allen, John G; Shu, Hong; Fotsch, Christopher; Bartberger, Michael D; Kim, Ki-Won; Komorowski, Renee; Graham, Melissa; Busby, James; Wang, Minghan; Meyer, James; Xu, Yang; Salyers, Kevin; Fielden, Mark; Véniant, Murielle M; Gu, Wei

    2013-12-27

    Acetyl-CoA carboxylase (ACC) is a target of interest for the treatment of metabolic syndrome. Starting from a biphenyloxadiazole screening hit, a series of piperazine oxadiazole ACC inhibitors was developed. Initial pharmacokinetic liabilities of the piperazine oxadiazoles were overcome by blocking predicted sites of metabolism, resulting in compounds with suitable properties for further in vivo studies. Compound 26 was shown to inhibit malonyl-CoA production in an in vivo pharmacodynamic assay and was advanced to a long-term efficacy study. Prolonged dosing with compound 26 resulted in impaired glucose tolerance in diet-induced obese (DIO) C57BL6 mice, an unexpected finding. PMID:24294923

  2. Akinleye Olaolu Alawode Oxidative Degradation of Piperazine in the

    E-print Network

    Rochelle, Gary T.

    #12;Copyright by Akinleye Olaolu Alawode 2005 #12;Oxidative Degradation of Piperazine of Master of Science in Engineering The University of Texas at Austin May, 2005 #12;Oxidative Degradation every step of the way. I love you very much. May 2005 Austin, Texas #12;vi Oxidative Degradation

  3. Degradation of aqueous piperazine in carbon dioxide capture

    Microsoft Academic Search

    Stephanie A. Freeman; Jason Davis; Gary T. Rochelle

    2010-01-01

    Concentrated, aqueous piperazine (PZ) is a novel solvent for carbon dioxide (CO2) capture by absorption\\/stripping. One of the major advantages of PZ is its resistance to thermal degradation and oxidation.At 135 and 150°C, 8m PZ is up to two orders of magnitude more resistant to thermal degradation than 7m monoethanolamine (MEA). After 18 weeks at 150°C, only 6.3% of the

  4. Survey and Down-Selection of Acid Gas Removal Systems for the Thermochemical Conversion of Biomass to Ethanol with a Detailed Analysis of an MDEA System

    Microsoft Academic Search

    Nexant

    2011-01-01

    The first section (Task 1) of this report by Nexant includes a survey and screening of various acid gas removal processes in order to evaluate their capability to meet the specific design requirements for thermochemical ethanol synthesis in NREL's thermochemical ethanol design report (Phillips et al. 2007, NREL\\/TP-510-41168). MDEA and selexol were short-listed as the most promising acid-gas removal agents

  5. John Arthur McLees, Jr. Vapor-Liquid Equilibrium of Monoethanolamine/Piperazine/Water at

    E-print Network

    Rochelle, Gary T.

    Copyright by John Arthur McLees, Jr. 2006 #12;Vapor-Liquid Equilibrium of Monoethanolamine/Piperazine/Water in Engineering The University of Texas at Austin May, 2006 #12;Vapor-Liquid Equilibrium of Monoethanolamine/Piperazine/Water games, and road trips that I am very excited to be staying here in Austin to watch him progress through

  6. Hepatotoxicity of piperazine designer drugs: Comparison of different in vitro models.

    PubMed

    Dias-da-Silva, D; Arbo, M D; Valente, M J; Bastos, M L; Carmo, H

    2015-08-01

    Piperazine derived drugs emerged on the drug market in the last decade. The aim of this study was to investigate in vitro the potential hepatotoxicity of the designer drugs N-benzylpiperazine (BZP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP), 1-(4-methoxyphenyl)piperazine (MeOPP) and 1-(3,4-methylenedioxybenzyl)piperazine (MDBP) in two human hepatic cell lines (HepaRG and HepG2) and in primary rat hepatocytes. Cell death was evaluated by the MTT assay, after 24h-incubations. Among the tested drugs, TFMPP was the most cytotoxic. HepaRG cells and primary hepatocytes revealed to be the most and the least resistant cellular models, respectively. To ascertain whether the CYP450 metabolism could explain their higher susceptibility, primary hepatocytes were co-incubated with the piperazines and the CYP450 inhibitors metyrapone and quinidine, showing that CYP450-mediated metabolism contributes to the detoxification of these drugs. Additionally, the intracellular contents of reactive species, ATP, reduced (GSH) and oxidized (GSSG) glutathione, changes in mitochondrial membrane potential (??m) and caspase-3 activation were further evaluated in primary cells. Overall, an increase in reactive species formation, followed by intracellular GSH and ATP depletion, loss of ??m and caspase-3 activation was observed for all piperazines, in a concentration-dependent manner. In conclusion, piperazine designer drugs produce hepatic detrimental effects that can vary in magnitude among the different analogues. PMID:25863214

  7. 1-Methyl­piperazine-1,4-diium dipicrate

    PubMed Central

    Dutkiewicz, Grzegorz; Samshuddin, S.; Narayana, B.; Yathirajan, H. S.; Kubicki, Maciej

    2011-01-01

    In the crystal structure of the title compound [systematic name: 1-methyl­piperazine-1,4-diium bis­(2,4,6-trinitro­phen­ol­ate)], C5H14N2 2+·2C6H2N3O7 ?, the ionic components are connected by relatively strong N—H?O hydrogen bonds into centrosymmetric six-membered conglomerates, which comprise two dications and four anions. Besides Coulombic inter­actions, only weak C—H?O inter­actions and some stacking between picrates (separation between the planes of ca. 3.4?Å but only a small overlapping) can be identified between these ‘building blocks’ of the crystal structure. The piperazine ring adopts a chair conformation with the methyl substituent in the equatorial position. In the picrate anions, the twist angles of the nitro groups depend on their positions relative to the phenolate O atom: it is much smaller for the NO2 groups para to the C—O? group [15.23?(9)and 3.92?(14)°] than for the groups in the ortho positions [28.76?(13)–39.84?(11)°]. PMID:21523064

  8. The Reaction of Piperazine2,5-dione with 2-Formylbenzoic Acid

    Microsoft Academic Search

    Margaret L. Baron; Ian D. Rae; Peta M. Simmonds

    Reaction of piperazine-2,5-dione with 2-formylbenzoic acid in the presence of triethylamine gives three products: 1-(3'-oxo-1',3'-dihydroisobenzofuran-l'-yl)piperazine-2,5-dione, its 1,4-bis analogue which had previously been identified as the 3,6-compound, and 2,2'-(3,6-dioxopiperazine-2,5-diylidene- bis(methylidyne))bis(benzoic acid). The latter compound is shown by 'H and 13C n.m.r, spectroscopy to be the Z,Z isomer. From the reaction of piperazine-2,5-dione with 2-formylbenzoic we have isolated three products. The first

  9. Pharmacological profiles of aminoindanes, piperazines, and pipradrol derivatives.

    PubMed

    Simmler, Linda D; Rickli, Anna; Schramm, York; Hoener, Marius C; Liechti, Matthias E

    2014-03-15

    Aminoindanes, piperazines, and pipradrol derivatives are novel psychoactive substances found in "Ecstasy" tablets as replacements for 3,4-methylenedioxymethamphetamine (MDMA) or substances sold as "ivory wave." The pharmacology of these MDMA- and methylphenidate-like substances is poorly known. We characterized the pharmacology of the aminoindanes 5,6-methylenedioxy-2-aminoindane (MDAI), 5-iodoaminoindane (5-IAI), and 2-aminoindane (2-AI), the piperazines meta-chlorophenylpiperazine (m-CPP), trifluoromethylphenylpiperazine (TFMPP), and 1-benzylpiperazine (BZP), and the pipradrol derivatives desoxypipradrol (2-diphenylmethylpiperidine [2-DPMP]), diphenylprolinol (diphenyl-2-pyrrolidinemethanol [D2PM]), and methylphenidate. We investigated norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine [5-HT]) uptake inhibition using human embryonic kidney 293 (HEK 293) cells that express the respective human monoamine transporters (NET, DAT, and SERT). We also evaluated the drug-induced efflux of NE, DA, and 5-HT from monoamine-preloaded cells and the binding affinity to monoamine transporters and receptors, including trace amine-associated receptor 1 (TAAR1). 5-IAI and MDAI preferentially inhibited the SERT and NET and released 5-HT. 2-AI interacted with the NET. BZP blocked the NET and released DA. m-CPP and TFMPP interacted with the SERT and serotonergic receptors. The pipradrol derivatives were potent and selective catecholamine transporter blockers without substrate releasing properties. BZP, D2PM, and 2-DPMP lacked serotonergic activity and TAAR1 binding, in contrast to the aminoindanes and phenylpiperazines. In summary, all of the substances were monoamine transporter inhibitors, but marked differences were found in their DAT vs. SERT inhibition profiles, release properties, and receptor interactions. The pharmacological profiles of D2PM and 2-DPMP likely predict a high abuse liability. PMID:24486525

  10. Separation and detection of ammonia, amines, and alkanolamines with single-column ion chromatography. [Alkylamines, ethanolamine and methyldiethanolamine

    SciTech Connect

    Poulson, R.E.; Borg, H.M.

    1986-03-01

    A single-column ion chromatographic method was developed for separation and detection of aqueous ammonia, C/sub 1/-, C/sub 2/-, and C/sub 3/- alkylamines, ethanolamine, and methyldiethanolamine. A precolumn concentrator was used to take detection of ammonium ion by electrical conductivity to fractional ppB levels and detection of the organic cations to ppB levels. Analysis of ppM ammonia levels in 3 wt % alkanolamine scrubber-type solutions was possible, but resolution of alkylamines was lost. A post-column reaction system for fluorescence detection of primary amine o-phthalaldehyde derivatives with reversed-phase separation allowed amine separation in the presence of large amounts of ammonia. The same system might be used in place of concentration and conductivity for determination of the alkylamine levels. A large variety of oil shale retort by-product waters and one underground coal gasification condensate were screened for alkylamines, but none were detected. 7 refs., 8 figs., 1 tab.

  11. Piperazine designer drugs induce toxicity in cardiomyoblast h9c2 cells through mitochondrial impairment.

    PubMed

    Arbo, Marcelo Dutra; Silva, Renata; Barbosa, Daniel José; da Silva, Diana Dias; Rossato, Luciana Grazziotin; Bastos, Maria de Lourdes; Carmo, Helena

    2014-08-17

    Abuse of synthetic drugs is widespread among young people worldwide. In this context, piperazine derived drugs recently appeared in the recreational drug market. Clinical studies and case-reports describe sympathomimetic effects including hypertension, tachycardia, and increased heart rate. Our aim was to investigate the cytotoxicity of N-benzylpiperazine (BZP), 1-(3-trifluoromethylphenyl) piperazine (TFMPP), 1-(4-methoxyphenyl) piperazine (MeOPP), and 1-(3,4-methylenedioxybenzyl) piperazine (MDBP) in the H9c2 rat cardiac cell line. Complete cytotoxicity curves were obtained at a 0-20 mM concentration range after 24 h incubations with each drug. The EC50 values (?M) were 343.9, 59.6, 570.1, and 702.5 for BZP, TFMPP, MeOPP, and MDBP, respectively. There was no change in oxidative stress markers. However, a decrease in total GSH content was noted for MDBP, probably due to metabolic conjugation reactions. All drugs caused significant decreases in intracellular ATP, accompanied by increased intracellular calcium levels and a decrease in mitochondrial membrane potential that seems to involve the mitochondrial permeability transition pore. The cell death mode revealed early apoptotic cells and high number of cells undergoing secondary necrosis. Among the tested drugs, TFMPP seems to be the most potent cytotoxic compound. Overall, piperazine designer drugs are potentially cardiotoxic and support concerns on risks associated with the intake of these drugs. PMID:24968061

  12. 1-Phenyl-piperazine-1,4-diium tetra-chlorido-cobalt(II).

    PubMed

    Dhieb, Abdelhamid Chiheb; Janzen, Daron E; Rzaigui, Mohamed; Smirani Sta, Wajda

    2014-04-01

    In the title mol-ecular salt, (C10H16N2)[CoCl4], the piperazine ring of the phenyl-piperazine dication adopts a chair conformation and the phenyl ring occupies an equatorial orientation. In the tetra-chlorido-cobaltate(II) dianion, the Co-Cl bond lengths for the chloride ions not accepting hydrogen bonds are significantly shorter than those for the chloride ions accepting such bonds. In the crystal, the components are linked by N-H?Cl hydrogen bonds, generating [001] chains. PMID:24826100

  13. Thermal decomposition reactions of cotton fabric treated with piperazine-phosphonates derivatives as a flame retardant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There has been a great scientific interest in exploring the great potential of the piperazine-phosphonates in flame retardant (FR) application on cotton fabric by investigating the thermal decomposition of cotton fabric treated with them. This research tries to understand the mode of action of the t...

  14. The influences of piperazine-phosphonates derivatives on flame retardancy and thermal behaviors of cotton cellulose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In an effort to create the environmentally-friendly flame retardants (FRs) for cotton cellulose, two phosphoramidates derivatives, tetraethyl piperazine-1,4-diyldiphosphonate (PDP) and diethyl 4-methylpiperazin-1-ylphosphoramidate (PAP), have been developed. Both were synthesized in high yield and ...

  15. The mechanism of action of piperazine-phosphonates derivatives in cotton fabric

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Piperazine-phosphonates additives are known to be very effective flame retardants on different polymeric systems, especially cotton cellulose. In order to understand their mechanism of action, we carried out the investigation of their thermal behavior on cotton fabric by, first, employing the attenu...

  16. Preparation of quinoxalines, dihydropyrazines, pyrazines and piperazines using tandem oxidation processes.

    PubMed

    Raw, Steven A; Wilfred, Cecilia D; Taylor, Richard J K

    2003-09-21

    Alpha-hydroxyketones undergo MnO2-mediated oxidation followed by in situ trapping with aromatic or aliphatic 1,2-diamines to give quinoxalines or dihydropyrazines, respectively, in a one pot procedure which avoids the need to isolate the highly reactive 1,2-dicarbonyl intermediates. Modifications of the procedure allow the formation of pyrazines and piperazines. PMID:14518877

  17. Piperazine-phosphonate derivatives: their flame retardant and thermal degradation properties on cotton fibers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been known that phosphorus-nitrogen system shows greater flame resistance in cotton textiles at a lower level than phosphorus used alone. This research aims to compare the effectiveness of Tetraethyl piperazine-1,4-diyldiphosphonate (TEPP) as a flame retardant (FR) for cotton fabric to a prev...

  18. Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

    PubMed Central

    Ingham, Richard J; Battilocchio, Claudio; Hawkins, Joel M

    2014-01-01

    Summary Here we describe the use of a new open-source software package and a Raspberry Pi® computer for the simultaneous control of multiple flow chemistry devices and its application to a machine-assisted, multi-step flow preparation of pyrazine-2-carboxamide – a component of Rifater®, used in the treatment of tuberculosis – and its reduced derivative piperazine-2-carboxamide. PMID:24778715

  19. Biochip array technology immunoassay performance and quantitative confirmation of designer piperazines for urine workplace drug testing.

    PubMed

    Castaneto, Marisol S; Barnes, Allan J; Concheiro, Marta; Klette, Kevin L; Martin, Thomas A; Huestis, Marilyn A

    2015-06-01

    Designer piperazines are emerging novel psychoactive substances (NPS) with few high-throughput screening methods for their identification. We evaluated a biochip array technology (BAT) immunoassay for phenylpiperazines (PNP) and benzylpiperazines (BZP) and analyzed 20,017 randomly collected urine workplace specimens. Immunoassay performance at recommended cutoffs was evaluated for PNPI (5 ?g/L), PNPII (7.5 ?g/L), and BZP (5 ?g/L) antibodies. Eight hundred forty positive and 206 randomly selected presumptive negative specimens were confirmed by liquid chromatography high-resolution mass spectrometry (LC-HRMS). Assay limits of detection for PNPI, PNPII, and BZP were 2.9, 6.3, and 2.1 ?g/L, respectively. Calibration curves were linear (R (2)?>?0.99) with upper limits of 42 ?g/L for PNPI/PNII and 100 ?g/L for BZP. Quality control samples demonstrated imprecision <19.3 %CV and accuracies 86.0-94.5 % of target. There were no interferences from 106 non-piperazine substances. Seventy-eight of 840 presumptive positive specimens (9.3 %) were LC-HRMS positive, with 72 positive for 1-(3-chlorophenyl)piperazine (mCPP), a designer piperazine and antidepressant trazodone metabolite. Of 206 presumptive negative specimens, one confirmed positive for mCPP (3.3 ?g/L) and one for BZP (3.6 ?g/L). BAT specificity (21.1 to 91.4 %) and efficiency (27.0 to 91.6 %) increased, and sensitivity slightly decreased (97.5 to 93.8 %) with optimized cutoffs of 25 ?g/L PNPI, 42 ?g/L PNPI, and 100 ?g/L BZP. A high-throughput screening method is needed to identify piperazine NPS. We evaluated performance of the Randox BAT immunoassay to identify urinary piperazines and documented improved performance when antibody cutoffs were raised. In addition, in randomized workplace urine specimens, all but two positive specimens contained mCPP and/or trazodone, most likely from legitimate medical prescriptions. Graphical Abstract Biochip array technology (BAT) immunoassay for designer piperazines detection in urine. In chemiluminescent immunoassay, the labeled-drug (antigen) competes with the drug in the urine. In the absence of drug, the labeled-drug binds to the antibody releasing an enzyme (horseradish peroxidase) to react with the substrate and producing chemiluminescence. The higher the drug concentration in urine, the weaker the chemiluminescent signal is produced. All presumptive positive specimens and randomly selected presumptive negative specimens were analyzed and confirmed by a liquid chromatography high-resolution mass spectrometry with limit of quantification of 2.5 or 5 ?g/L. PMID:25903022

  20. A novel route for the synthesis of piperazine from N-(2,3-dihydroxypropyl)ethylenediamine over composite photocatalysts.

    PubMed

    Subba Rao, K V; Kandavelu, V; Srinivas, B; Subrahmanyam, M; Thampi, K Ravindranathan

    2003-11-01

    Semiconductor loaded zeolite composite catalysts (5 wt% TiO2/Hbeta) have been used to photocatalytically synthesize piperazine from N-(2,3-dihydroxypropyl)ethylenediamine with yields up to 59.0 mol%. PMID:14649821

  1. Thermodynamic Study of Corrosion and Inhibitor Adsorption Processes onto C38 Steel\\/piperazines\\/phosphoric Acid Systems

    Microsoft Academic Search

    A. Ousslim; A. Ouniti; K. Bekkouch; A. Elidrissi; B. Hammouti

    2009-01-01

    This paper describes the inhibition effect of 1-benzyl piperazine (P1) and bis(1-benzyl piperazine) thiuram disulfide (P2) towards the corrosion of C38 steel in 5.5 M H3PO4 solution by potentiodynamic polarization and weight loss methods. The influence of inhibitor concentration and temperature on inhibitory behavior of P2 were investigated. The inhibition efficiency (IE) was found to be dependent on the type

  2. Novel 1-(2-aryl-2-adamantyl)piperazine derivatives with antiproliferative activity.

    PubMed

    Fytas, Christos; Zoidis, Grigoris; Tsotinis, Andrew; Fytas, George; Khan, Mohsin A; Akhtar, Samar; Rahman, Khondaker M; Thurston, David E

    2015-03-26

    Novel 1-(2-aryl-2-adamantyl)piperazine derivatives have been synthesized and evaluated in vitro for their antitumor properties against HeLa cervical carcinoma, MDA MB 231 breast cancer, MIA PaCa2 pancreatic cancer, and NCI H1975 non-small cell lung cancer. The parent piperazine 6 was found to exhibit a reasonable activity toward the HeLa and MDA MB 231 tumor cell lines (IC50= 9.2 and 8.4 ??, respectively). Concurrent benzene ring C4-fluorination and piperidine acetylation of the piperazino NH of compound 6 resulted in the most active compound 13 of the series in both of the above cell lines (IC50=8.4 and 6.8 ??, respectively). Noticeably, compounds 6 and 13 exhibited a significantly low cytotoxicity level over the normal human cells HUVEC (Human Umbilical Vein Endothelial Cells) and NHDF (Normal Human Dermal Fibroblasts). PMID:25703296

  3. Tri-chlorido-(1-ethyl-piperazin-1-ium)cobalt(II).

    PubMed

    Dhieb, Abdelhamid Chiheb; Janzen, Daron E; Rzaigui, Mohamed; Smirani Sta, Wajda

    2014-05-01

    In the title complex, [Co(C6H15N2)Cl3], the Co(2+) ion is coordinated in a distorted tetra-hedral fashion by three chloride ions and one N atom of the piperazine ring; the ring adopts a chair conformation with the N-Co and N-CEt bonds in equatorial orientations. In the crystal, mol-ecules are connected by N-H?Cl hydrogen bonds, generating (10-1) sheets. PMID:24860302

  4. 1-(2-Pyrimidinyl)Piperazine as Active Metabolite of Buspirone in Man and Rat

    Microsoft Academic Search

    Silvio Caccia; Ivana Conti; Gianluigi Viganò; Silvio Garattini

    1986-01-01

    Buspirone (BP), a newly developed antianxiety agent, forms 1-(2-pyrimidinyl)-piperazine (PmP) during its biotransformation in rats and man. After oral administration of pharmacologically effective doses of BP-hydrochloride to rats (1 and 10 mg\\/kg), the metabolite appears in significant amounts in body fluids and tissues; it is highly concentrated in the central nervous system, the brain-to-plasma concentration ratios being approximately 5 at

  5. Multimetallic assemblies using piperazine-based dithiocarbamate building blocks.

    PubMed

    Wilton-Ely, James D E T; Solanki, Dina; Knight, Edward R; Holt, Katherine B; Thompson, Amber L; Hogarth, Graeme

    2008-10-20

    Treatment of cis-[RuCl2(dppm)2] (dppm = bis(diphenylphosphino)methane) with dithiocarbamates, NaS2CNR2 (R = Me, Et) and [H2NC5H10][S2CNC5H10], yields cations [Ru(S2CNR2)2(dppm)2](+) and [Ru(S2CNC5H10)2(dppm)2](+), respectively. The zwitterions S2CNC4H8NHR (R = Me, Et) react with the same metal complex in the presence of base to yield [Ru(S2CNC4H8NR)(dppm)2](+). Piperazine or 2,6-dimethylpiperazine reacts with carbon disulfide to give the zwitterionic dithiocarbamate salts H2NC4H6(R2-3,5)NCS2 (R = H; R = Me), which form the complexes [Ru(S2CNC4H6(R2-3,5)NH2)(dppm)2](2+) on reaction with cis-[RuCl2(dppm)2]. Sequential treatment of [Ru(S2CNC4H8NH2)(dppm)2](2+) with triethylamine and carbon disulfide forms the versatile metalla-dithiocarbamate complex [Ru(S2CNC4H8NCS2)(dppm)2] which reacts readily with cis-[RuCl2(dppm)2] to yield [{Ru(dppm)2}2(S2CNC4H8NCS2)]. Reaction of [Ru(S2CNC4H8NCS2)(dppm)2] with [Os(CH=CHC6H4Me-4)Cl(CO)(BTD)(PPh3)2] (BTD = 2,1,3-benzothiadiazole), [Pd(C6H4CH2NMe2)Cl]2, [PtCl2(PEt3)2], and [NiCl2(dppp)] (dppp = 1,3-bis(diphenylphosphino)propane) results in the heterobimetallic complexes [(dppm)2Ru(S2CNC4H8NCS2)ML(n))](m+) (ML(n) = Os(CH=CHC6H4Me-4)(CO)(PPh3)2](+), m = 1; ML(n) = Pd(C,N-C6H4CH2NMe2), m = 1; ML(n) = Pt(PEt3)2, m = 2; ML(n) = Ni(dppp), m = 2). Reaction of [NiCl2(dppp)] with H2NC4H8NCS2 yields the structurally characterized compound, [Ni(S2CNC4H8NH2)(dppp)](2+), which reacts with base, CS2, and cis-[RuCl2(dppm)2] to provide an alternative route to [(dppm)2Ru(S2CNC4H8NCS2)Ni(dppp)](+). A further metalla-dithiocarbamate based on cobalt, [CpCo(S2CNC4H8NH2)(PPh3)](2+), is formed by treatment of CpCoI2(CO) with S2CNC4H8NH2 followed by PPh3. Further reaction with NEt3, CS2, and cis-[RuCl2(dppm)2] yields [(Ph3P)CpCo(S2CNC4H8NCS2)Ru(dppm)2](2+). Heterotrimetallic species of the form [{(dppm)2Ru(S2CNC4H8NCS2)}2M](2+) result from the reaction of [Ru(S2CNC4H8NCS2)(dppm)2] and M(OAc)2 (where M = Ni, Cu, Zn). Reaction of [Ru(S2CNC4H8NCS2)(dppm)2] with Co(acac)3 and LaCl3 results in the formation of the compounds [{(dppm)2Ru(S2CNC4H8NCS2)}3Co](3+) and [{(dppm)2Ru(S2CNC4H8NCS2)}3La](3+), respectively. The electrochemical behavior of selected examples is also reported. PMID:18811147

  6. Molecular Solids from Symmetrical Bis(piperazine-2,5-diones) with Open and Closed Monomer Conformations.

    PubMed

    Polaske, Nathan W; Nichol, Gary S; Szabó, Lajos Z; Olenyuk, Bogdan

    2009-04-01

    The design, synthesis and solid state structures of a new class of xylylene-linked bis(1,4- piperazine-2,5-diones) are reported in an effort to extend the molecular framework of piperazine-2,5-diones. These compounds were derived from piperazine-2,5-dione as the core structure, synthesized via a new efficient route, and their crystal structures were determined. We examined the effects of side chain substitution on conformations of the linked bis-DKPs. Crystallization of 3,3'-[1,4-phenylenebis(methylene)]-bis[6-(hydroxymethyl)-1,4-dimethylpiperazine-2,5-dione] yielded molecular solids with an unusual network of "C"-shaped monomers held together by four intermolecular hydrogen bonds per asymmetric unit. Similarly, intermolecular interactions between the iodomethyl groups in 3,3'-[1,4-phenylenebis(methylene)]-bis[6-(iodomethyl)-1,4-dimethyl-piperazine-2,5-dione] result in the monomers adopting a "C"-shape in the solid state. Assembly of the monomers with side chains converted to methyl groups or tert-butyldimethylsilyl ethers, thereby lacking these stabilizing intermolecular interactions, results in an infinite array of "S"-shaped conformations. These results suggest that the interplay between the attractive intermolecular interactions and repulsive steric interactions of the substituents at the C6 and C6' positions of the diketopiperazine rings is important in determining the solid-state conformations of xylylene-linked bis(piperazine-2,5-diones). PMID:20161254

  7. Molecular Solids from Symmetrical Bis(piperazine-2,5-diones) with Open and Closed Monomer Conformations

    PubMed Central

    Polaske, Nathan W.; Nichol, Gary S.; Szabó, Lajos Z.; Olenyuk, Bogdan

    2009-01-01

    The design, synthesis and solid state structures of a new class of xylylene-linked bis(1,4- piperazine-2,5-diones) are reported in an effort to extend the molecular framework of piperazine-2,5-diones. These compounds were derived from piperazine-2,5-dione as the core structure, synthesized via a new efficient route, and their crystal structures were determined. We examined the effects of side chain substitution on conformations of the linked bis-DKPs. Crystallization of 3,3'-[1,4-phenylenebis(methylene)]-bis[6-(hydroxymethyl)-1,4-dimethylpiperazine-2,5-dione] yielded molecular solids with an unusual network of “C”-shaped monomers held together by four intermolecular hydrogen bonds per asymmetric unit. Similarly, intermolecular interactions between the iodomethyl groups in 3,3'-[1,4-phenylenebis(methylene)]-bis[6-(iodomethyl)-1,4-dimethyl-piperazine-2,5-dione] result in the monomers adopting a “C”-shape in the solid state. Assembly of the monomers with side chains converted to methyl groups or tert-butyldimethylsilyl ethers, thereby lacking these stabilizing intermolecular interactions, results in an infinite array of “S”-shaped conformations. These results suggest that the interplay between the attractive intermolecular interactions and repulsive steric interactions of the substituents at the C6 and C6' positions of the diketopiperazine rings is important in determining the solid-state conformations of xylylene-linked bis(piperazine-2,5-diones). PMID:20161254

  8. A modular lead-oriented synthesis of diverse piperazine, 1,4-diazepane and 1,5-diazocane scaffolds.

    PubMed

    James, Thomas; Maclellan, Paul; Burslem, George M; Simpson, Iain; Grant, J Andrew; Warriner, Stuart; Sridharan, Visuvanathar; Nelson, Adam

    2014-04-28

    Piperazines are found widely in commercially-available compounds and bioactive molecules (including many drugs). However, in the vast majority of these molecules, the piperazine ring is isolated (i.e. not fused to another ring) and is not substituted on any of its carbon atoms. A modular synthetic approach is described in which combinations of cyclic sulfamidate and hydroxy sulfonamide building blocks may be converted into piperazines and related 1,4-diazepine and 1,5-diazocane scaffolds. By variation of the combinations of building blocks used, it was possible to vary the ring size, substitution and configuration of the resulting heterocyclic scaffolds. The approach was exemplified in the synthesis of a range of heterocyclic scaffolds that, on decoration, would target lead-like chemical space. It was demonstrated that lead-like small molecules based on these scaffolds would likely complement those found in large compound collections. PMID:24614952

  9. Piperazine modification in 2,4,6-triaminopyrimidine derivatives as histamine H4 receptor ligands.

    PubMed

    Schreeb, A; Walter, M; Odadzic, D; Schwed, J S; Weizel, L; Stark, H

    2013-07-01

    The human histamine H4 receptor (hH4R) is a promising new target in the therapy of inflammatory and immunomodulatory diseases. The 2,4,6-triaminopyrimidine structure has been established as a potent hH4R affinity scaffold. By using the inverse agonist ST-1012 as reference ligand, piperazine modifications were performed to get larger structural variations. Therefore, different spacers were introduced into the lead structure and the influence on affinity of this basic element was evaluated. While a short distance between aminopyrimidine and basic moiety is beneficial, a lipophilic group in the eastern part is necessary to maintain hH4R affinity. PMID:23923631

  10. Synthesis, pharmacological evaluation, and ?1 receptor interaction analysis of hydroxyethyl substituted piperazines.

    PubMed

    Weber, Frauke; Brune, Stefanie; Korpis, Katharina; Bednarski, Patrick J; Laurini, Erik; Dal Col, Valentina; Pricl, Sabrina; Schepmann, Dirk; Wünsch, Bernhard

    2014-04-10

    Starting from (S)- or (R)-aspartate, three synthetic strategies were explored to prepare hydroxyethyl substituted piperazines with different substituents at the N-atoms. ? receptor affinity was recorded using receptor material from both animal and human origin. ?1 affinities determined with guinea pig brain and human RPMI 8226 tumor cell lines differed slightly but showed the same tendency. (S)-2-[4-(Cyclohexylmethyl)-1-(naphthalene-2-ylmethyl)piperazin-2-yl]ethanol (7c) revealed the highest affinity at human ?1 receptors (Ki = 6.8 nM). The potent ?1 receptor ligand 7c was able to inhibit selectively the growth of three human tumor cell lines with IC50 values in the low micromolar range. The reduced growth of the RPMI-8226 cell line was caused by apoptosis. The interaction of 7c with the ?1 receptor was analyzed in detail using the 3D homology model of the ?1 receptor. The calculated free binding energies of all hydroxyethylpiperazines nicely correlate with their recorded affinities toward the human ?1 receptor. PMID:24617836

  11. Enantiomeric separation and quantitation of (+/-)-amphetamine, (+/-)-methamphetamine, (+/-)-MDA, (+/-)-MDMA, and (+/-)-MDEA in urine specimens by GC-EI-MS after derivatization with (R)-(-)- or (S)-(+)-alpha-methoxy-alpha-(trifluoromethy)phenylacetyl chloride (MTPA).

    PubMed

    Paul, Buddha D; Jemionek, John; Lesser, David; Jacobs, Aaron; Searles, Douglas A

    2004-09-01

    In drug testing, the presence of methamphetamine in urine is generally confirmed by a gas chromatography-mass spectrometry (GC-MS) method. Derivatization of the compound to a perfluoroalkylamide, prior to confirmation, typically yields better chromatographic separation. Once methamphetamine is detected, a second GC-MS test is necessary to distinguish positive results from the use of over-the-counter medication, Vicks inhaler, or from use of a prescription drug, selegiline (Deprenyl). R-(-)-Methamphetamine is the urinary product from legitimate use of these medications. The second GC-MS test is to confirm illicit use of (S)-(+)-methamphetamine. In the procedure, the two methamphetamine isomers are changed to the chromatographically separable diastereomers by a chiral derivatizing agent, (S)-(-)-trifluoroacetylprolyl chloride (TPC). But the method has inherent limitations. Racemization of the reagent produces mixed diastereomers even from pure (S)-(+)-methamphetamine. Instead of using TPC, we utilized (R)-(-)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride (MTPA) to prepare the amides of diastereomers of methamphetamine. No racemization was observed with this reagent. The method was extended to resolve GC peaks of (R)-(-)- and (S)-(+)-isomers of amphetamine, 3,4-methylenedioxyamphetamine (MDA), N-methyl-MDA (MDMA), and N-ethyl-MDA (MDEA). Three ions from the drug and two ions from the deuterated internal standard were monitored to characterize and quantitate the drugs. For MDEA, only one ion was used. The quantitation was linear over 25 to 5000 ng/mL for MDEA and 25 to 10,000 ng/mL for all other drugs. Correlation coefficients were > 0.996. Precision calculated as the coefficient of variation at the calibrator concentration of 500 ng/mL was within +/- 11% for all drugs. The method was applied to test 43 urine specimens. In 91% of the methamphetamine-positive specimens, only the (S)-(+)-isomer was detected. In all MDMA-positive specimens, the concentrations of (R)-(-)-isomer were greater than the (S)-(+)-isomer indicating longer retention of (R)-(-)-isomer in the human body. The specimen concentrations (R + S) compared well with that of a non-chiral method that used 4-carboethoxyhexafluorobutyryl chloride as derivatizing agent. But the MTPA method has some advantage. It alone can replace the two GC-MS methods needed to confirm the presence of (S)-(+)-isomers of amphetamine and methamphetamine. PMID:15516295

  12. Synthesis and SAR of piperazine amides as novel c-jun N-terminal kinase (JNK) inhibitors

    SciTech Connect

    Shin, Youseung; Chen, Weiming; Habel, Jeff; Duckett, Derek; Ling, Yuan Yuan; Koenig, Marcel; He, Yuanjun; Vojkovsky, Tomas; LoGrasso, Philip; Kamenecka, Theodore M.; (Scripps)

    2009-09-14

    A novel series of c-jun N-terminal kinase (JNK) inhibitors were designed and developed from a high-throughput-screening hit. Through the optimization of the piperazine amide 1, several potent compounds were discovered. The X-ray crystal structure of 4g showed a unique binding mode different from other well known JNK3 inhibitors.

  13. Solubility of carbon dioxide in aqueous mixtures of alkanolamines

    SciTech Connect

    Dawodu, O.F.; Meisen, A. (Univ. of British Columbia, Vancouver, British Columbia (Canada). Dept. of Chemical Engineering)

    1994-07-01

    The solubility of CO[sub 2] in water + N-methyldiethanolamine + monoethanolamine (MDEA + MEA) and water + N-methyldiethanolamine + diethanolamine (MDEA + DEA) are reported at two compositions of 3.4 M MDEA + 0.8 M MEA or DEA and 2.1 M MDEA + 2.1 M MEA or DEA at temperatures from 70 to 180 C and CO[sub 2] partial pressures from 100 to 3,850 kPa. The solubility of CO[sub 2] in the blends decreased with an increase in temperature but increased with an increase in CO[sub 2] partial pressure. At low partial pressures of CO[sub 2] and the same total amine concentration, the equilibrium CO[sub 2] loadings were in the order MDEA + MEA > MDEA + DEA > MDEA. However, at high CO[sub 2] partial pressures, the equilibrium CO[sub 2] loadings in the MDEA solutions were higher than those of the MDEA + MEA and MDEA + DEA blends of equal molar strengths due to the stoichiometric loading limitations of MEA and DEA. The nonadditivity of the equilibrium loadings for single amine systems highlights the need for independent measurements on amine blends.

  14. Acid gas treating by aqueous alkanolamines. Annual report, January-December 1993

    SciTech Connect

    Sandall, O.C.; Rinker, E.B.; Ashour, S.

    1993-12-01

    The objective of the work is to investigate the simultaneous absorption or desorption of CO2 and H2S into and from a mixed aqueous amine solvent consisting of methyldiethanolamine (MDEA) and diethanolamine (DEA). In work completed thus far, density, viscosity, gas diffusivity, gas solubility, surface tension, and amine solution vapor pressure have been measured for aqueous MDEA, DEA, and MDEA/DEA mixtures over the temperature range 20 to 100 deg. C and for concentrations up to 50 weight %. A mathematical model, based on the penetration theory, for the simultaneous absorption (desorption) of CO2 and H2S into (from) aqueous solutions of MDEA and DEA has been developed.

  15. Acid gas treating by aqueous alkanolamines. Annual report, July-December 1992

    SciTech Connect

    Sandall, O.C.; Rinker, E.B.; Tamimi, A.; Davis, R.A.; Oelschlager, D.W.

    1992-12-01

    The objective of the work is to investigate the simultaneous absorption or desorption of CO2 and H2S into and from a mixed aqueous amine solvent consisting of methyldiethanolamine (MDEA) and diethanolamine (DEA). In work completed thus far models have been developed for single gas (either H2S or CO2) absorption into a single amine solution (MDEA or DEA). Density and viscosity measurements have been made for aqueous MDEA, DEA and MDEA/DEA mixtures over the temperature range 20 to 100 C and for concentrations up to 50 weight %.

  16. Piperazine derivatives including the putative anxiolytic drugs, buspirone and ipsapirone, are agonists at 5HT1A receptors negatively coupled with adenylate cyclase in hippocampal neurons

    Microsoft Academic Search

    Joël Bockaert; Aline Dumuis; Rochdi Bouhelal; Michèle Sebben; Robert N. Cory

    1987-01-01

    Two putative anxiolytic drugs [ipsapirone (TVXQ 7821) and buspirone], structurally unrelated to benzodiazepines, have negligible ataxic and sedative side effects. These drugs are piperazine analogs which interact at 5-HT1 binding sites. It is demonstrated here that these drugs and two other piperazine derivatives, trifluoromethylphenylpiperazine (TFMPP) and m-chlorophenylpiperazine (mCPP), are agonists at 5-HT1A receptors, a subclass of the 5-HT1 receptor, mediating

  17. Vapor pressure measurements of bis(hydroxyethyl)piperazine and tris(hydroxyethyl)ethylenediamine

    SciTech Connect

    Abdi, M.A.; Meisen, A. [Univ. of British Columbia, Vancouver, British Columbia (Canada). Dept. of Chemical and Bio-Resource Engineering] [Univ. of British Columbia, Vancouver, British Columbia (Canada). Dept. of Chemical and Bio-Resource Engineering

    1998-03-01

    Aqueous solutions of diethanolamine (DEA) are commonly used to remove acid gases (including hydrogen sulfide and carbon dioxide) from natural, refinery, and other industrial gas streams. Vapor pressures of bis(hydroxyethyl)piperazine (BHEP) and tris(hydroxyethyl)ethylenediamine (THEED) were measured in the temperature ranges of (412.65 to 507.15) and (372.55 to 472.35) K using the static and gas saturation techniques, respectively. The experimental data are well represented by the modified Antoine and the integrated Clausius-Clapeyron equations, and their coefficients are reported. The enthalpies of vaporization were found to be (62.76 {+-} 5.33) and (89.96 {+-} 3.91) kJ/mol for BHEP and THEED, respectively.

  18. Solubility of carbon dioxide in an aqueous blend of diethanolamine and piperazine

    SciTech Connect

    Mondal, M.K. [Banaras Hindu University, Varanasi (India). Dept. of Chemical Engineering and Technology

    2009-09-15

    The solubility of CO{sub 2} in aqueous blends of diethanolamine (DEA) and piperazine (PZ), from mixtures of CO{sub 2} and N{sub 2}, was measured for temperatures and CO{sub 2} partial pressures ranging from (303.14 to 353.14) K and (10.133 to 20.265) kPa, respectively. Measurements were made by a saturation method using a laboratory scale bubble column. The results of CO{sub 2} solubility in liquid are expressed as {alpha}(CO{sub 2}) (mol CO{sub 2}/mol amine) for all experimental runs. A solubility model is developed to correlate and predict the solubility data of CO{sub 2} in aqueous blends of DEA and PZ. There is all acceptable degree of agreement between the experimental data of the present study and predictions of the solubility model with an average absolute deviation of less than 4.5%.

  19. Inhibition of adenovirus replication by a trisubstituted piperazin-2-one derivative.

    PubMed

    Sanchez-Cespedes, Javier; Moyer, Crystal L; Whitby, Landon R; Boger, Dale L; Nemerow, Glen R

    2014-08-01

    The number of disseminated adenovirus (Ad) infections continues to increase mostly due to the growing use of immunosuppressive treatments. Recipients of solid organ or hematopoietic stem cell transplants, mainly in pediatric units, exhibit a high morbidity and mortality due to these infections. Unfortunately, there are no Ad-specific antiviral drugs currently approved for medical use. To address this situation, we used high-throughput screening (HTS) of synthetic small molecule libraries to identify compounds that restrict Ad infection. Among the more than 25,000 compounds screened, we identified a hit compound that significantly inhibited Ad infection. The compound (15D8) is a trisubstituted piperazin-2-one derivative that showed substantial antiviral activity with little or no cytotoxicity at low micromolar concentrations. Compound 15D8 selectively inhibits Ad DNA replication in the nucleus, providing a potential candidate for the development of a new class of antiviral compounds to treat Ad infections. PMID:24907427

  20. Piperazine and piperidine triazole ureas as ultrapotent and highly selective inhibitors of monoacylglycerol lipase.

    PubMed

    Aaltonen, Niina; Savinainen, Juha R; Ribas, Casandra Riera; Rönkkö, Jani; Kuusisto, Anne; Korhonen, Jani; Navia-Paldanius, Dina; Häyrinen, Jukka; Takabe, Piia; Käsnänen, Heikki; Pantsar, Tatu; Laitinen, Tuomo; Lehtonen, Marko; Pasonen-Seppänen, Sanna; Poso, Antti; Nevalainen, Tapio; Laitinen, Jarmo T

    2013-03-21

    Monoacylglycerol lipase (MAGL) terminates the signaling function of the endocannabinoid, 2-arachidonoylglycerol (2-AG). During 2-AG hydrolysis, MAGL liberates arachidonic acid, feeding the principal substrate for the neuroinflammatory prostaglandins. In cancer cells, MAGL redirects lipid stores toward protumorigenic signaling lipids. Thus MAGL inhibitors may have great therapeutic potential. Although potent and increasingly selective MAGL inhibitors have been described, their number is still limited. Here, we have characterized piperazine and piperidine triazole ureas that combine the high potency attributable to the triazole leaving group together with the bulky aromatic benzodioxolyl moiety required for selectivity, culminating in compound JJKK-048 that potently (IC50 < 0.4 nM) inhibited human and rodent MAGL. JJKK-048 displayed low cross-reactivity with other endocannabinoid targets. Activity-based protein profiling of mouse brain and human melanoma cell proteomes suggested high specificity also among the metabolic serine hydrolases. PMID:23521796

  1. Discovery of novel Bcr-Abl inhibitors with diacylated piperazine as the flexible linker.

    PubMed

    Pan, Xiaoyan; Dong, Jinyun; Shi, Yaling; Shao, Ruili; Wei, Fen; Wang, Jinfeng; Zhang, Jie

    2015-07-01

    Forty-two compounds (series 8, 9 and 10) incorporated with diacylated piperazine have been synthesized and evaluated as novel Bcr-Abl inhibitors based on 'six-atom linker'. Five of them, 8d, 8h, 8l, 10m and 10p, displayed potent Bcr-Abl inhibitory activity comparable with Imatinib. Moreover, compounds 8e, 10q, 10s, and 10u were potent Bcr-Abl inhibitors with IC50 values at the sub-micromolecular level. Most compounds exhibited moderate to high antiproliferative activity against K562 cells. In particular, compound 9e was the most promising Bcr-Abl inhibitor. Docking studies revealed that the binding modes of these compounds were similar with Imatinib. These compounds could be considered as promising lead compounds for further optimization. PMID:26052668

  2. Increased serotonergic functions following adminstration of 1-(1-naphthyl) piperazine in propranolol injected rats.

    PubMed

    Perveen, Tahira; Rafiq, Roomana; Haider, Saida; Haleem, Darakhshan J

    2006-07-01

    Propranolol a beta adrenergic antagonist, binds with 5-HT1 receptor. 1-(1-naphthyl) piperazine (1-NP) a derivative of quipazine has serotonin antagonist activity at 5-HT2 and agonist activity at 5-HT1 site. In the present study neurochemical and behavioral effects of 1-NP was monitored in saline and propranolol injected rats. 1NP increased locomotor activity in saline as well as in propranolol injected rats. Administration of propranolol also increased locomotor activity and these increases were more enhanced following 1-NP administration. Levels of 5-HT were not altered following the administration of 1NP in saline as well as propranolol injected rats. 5-HT turnover however decreased by the administration of propranolol Adminstration of 1NP decreased 5-HT turnover in saline but not in propranolol injected rats. PMID:16935825

  3. LC-MS/MS screening method for designer amphetamines, tryptamines, and piperazines in serum.

    PubMed

    Wohlfarth, Ariane; Weinmann, Wolfgang; Dresen, Sebastian

    2010-04-01

    Since the late 1990s and early 2000s, derivatives of well-known designer drugs as well as new psychoactive compounds have been sold on the illicit drug market and have led to intoxications and fatalities. The LC-MS/MS screening method presented covers 31 new designer drugs as well as cathinone, methcathinone, phencyclidine, and ketamine which were included to complete the screening spectrum. All but the last two are modified molecular structures of amphetamine, tryptamine, or piperazine. Among the amphetamine derivatives are cathinone, methcathinone, 3,4-DMA, 2,5-DMA, DOB, DOET, DOM, ethylamphetamine, MDDMA, 4-MTA, PMA, PMMA, 3,4,5-TMA, TMA-6 and members of the 2C group: 2C-B, 2C-D, 2C-H, 2C-I, 2C-P, 2C-T-2, 2C-T-4, and 2C-T-7. AMT, DPT, DiPT, MiPT, DMT, and 5MeO-DMT are contained in the tryptamine group, BZP, MDBP, TFMPP, mCPP, and MeOPP in the piperazine group. Using an Applied Biosystems LC-MS/MS API 365 TurboIonSpray it is possible to identify all 35 substances. After addition of internal standards and mixed-mode solid-phase extraction the analytes are separated using a Synergi Polar RP column and gradient elution with 1 mM ammonium formate and methanol/0.1% formic acid as mobile phases A and B. Data acquisition is performed in MRM mode with positive electro spray ionization. The assay is selective for all tested substances. Limits of detection were determined by analyzing S/N-ratios and are between 1.0 and 5.0 ng/mL. Matrix effects lie between 65% and 118%, extraction efficiencies range from 72% to 90%. PMID:20069283

  4. Synthesis and Characterization of New Piperazine-Type Inhibitors for Mitochondrial NADH-Ubiquinone Oxidoreductase (Complex I)†

    PubMed Central

    Ichimaru, Naoya; Murai, Masatoshi; Kakutani, Nobuyuki; Kako, Junko; Ishihara, Atsushi; Nakagawa, Yoshiaki; Nishioka, Takaaki; Yagi, Takao; Miyoshi, Hideto

    2008-01-01

    The mode of action of ?lac-acetogenins, strong inhibitors of bovine heart mitochondrial complex I, is different from that of traditional inhibitors such as rotenone and piericidin A [Murai et al. (2007) Biochemistry 46, 6409?6416]. As further exploration of these unique inhibitors might provide new insights into the terminal electron transfer step of complex I, we drastically modified the structure of ?lac-acetogenins and characterized their inhibitory action. In particular, on the basis of structural similarity between the bis-THF and the piperazine rings, we here synthesized a series of piperazine derivatives. Some of the derivatives exhibited very potent inhibition at nanomolar levels. The hydrophobicity of the side chains and their balance were important structural factors for the inhibition, as is the case for the original ?lac-acetogenins. However, unlike in the case of the original ?lac-acetogenins: (i) the presence of two hydroxy groups is not crucial for the activity, (ii) the level of superoxide production induced by the piperazines is relatively high, (iii) the inhibitory potency for the reverse electron transfer is remarkably weaker than that for the forward event, and (iv) the piperazines efficiently suppressed the specific binding of a photoaffinity probe of natural-type acetogenins ([125I]TDA) to the ND1 subunit. It is therefore concluded that the action mechanism of the piperazine series differs from that of the original ?lac-acetogenins. Photoaffinity labeling study using a newly synthesized photoreactive piperazine ([125I]AFP) revealed that this compound binds to the 49 kDa subunit and an unidentified subunit, not ND1, with a frequency of about 1:3. A variety of traditional complex I inhibitors as well as ?lac-acetogenins suppressed the specific binding of [125I]AFP to the subunits. The apparent competitive behavior of inhibitors that seem to bind to different sites may be due to structural changes at the binding site, rather than occupying the same site. The meaning of the occurrence of diverse inhibitors exhibiting different mechanisms of action is discussed in the light of the functionality of the membrane arm of complex I. PMID:18781777

  5. DFT Study of Solvent Effects on Conformational Equilibria and Vibrational Spectra of 4-(1-PYRROLIDINYL)PIPERAZINE

    NASA Astrophysics Data System (ADS)

    Baglayan, O.; Kesan, G.; Parlak, C.; Senyel, M.

    2012-06-01

    The optimized structural parameters (bond lengths, bond and dihedral angles), conformational equilibria and normal mode frequencies and corresponding vibrational assignments of 4-(1-Pyrrolidinyl)piperazine (4-pypp) have been examined by means of B3LYP hybrid density functional theory (DFT) method with 6-31++G(d,p) basis set. Furthermore, reliable vibrational assignments have made on the basis of potential energy distribution (PED) calculated and the thermodynamics functions, highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO) of 4-pypp (C_8H17N_3) have been predicted. Calculations are employed for different conformations of 4-pypp both in gas phase and in solution. Solvent effects are investigated using chloroform and dimethylsulfoxide. Results from the theoretical values are showed that the structural parameters, mole fractions of stable conformers, vibrational frequencies, IR intensities and Raman activities of 4-pypp are solvent dependent. {Keywords}: 4-(1-Pyrrolidinyl)piperazine, vibrational spectra, solvent effect, DFT.

  6. Synthesis and antioxidant activity of some 1-aryl/aralkyl piperazine derivatives with xanthine moiety at N4

    PubMed Central

    Andonova, Lily; Zheleva-Dimitrova, Dimitrina; Georgieva, Maya; Zlatkov, Alexander

    2014-01-01

    Piperazine nucleus is one of the most important heterocyclic systems exhibiting remarkable pharmacological activities. Thus, in the current study six new aryl/aralkyl substituted piperazine derivatives, containing methylxanthine moiety were synthesized and their structures were confirmed by IR and 1H NMR analysis. All compounds were in vitro screened for their activity as antioxidants using DPPH (2,2?-Diphenyl-1-picrylhydrazyl), ABTS (2,2?-azinobis-(3-ethylbenzo thiazine-6-sulfonic acid)) and FRAP (ferric reducing/antioxidant power) methods. The antioxidant activity of the studied compounds against lipid peroxidation was also measured. The highest antioxidant activity was demonstrated by compound 3c. It is obvious that the presence of a hydroxyl group in the structure is essential for the antioxidant properties and should be taken into consideration in further design of structures with potential antioxidant properties. PMID:26019603

  7. Dual luminescence in solid CuI(piperazine): hypothesis of an emissive 1-D delocalized excited state.

    PubMed

    Maini, L; Braga, D; Mazzeo, P P; Maschio, L; Rérat, M; Manet, I; Ventura, B

    2015-07-14

    Solid [CuI(piperazine)0.5]?, characterized by a structure with an infinite double chain of CuI, presents an unexpected dual luminescence. The short copper-copper distances allow the existence of both cluster-centered and 1-D delocalized electronic transitions, as emerged from theoretical calculations. Beyond the more common cluster-centered emission a higher energy band, which differs in lifetime and in temperature dependence, is observed. PMID:26145149

  8. New Urea and Thiourea Derivatives of Piperazine Doped with Febuxostat: Synthesis and Evaluation of Anti-TMV and Antimicrobial Activities

    PubMed Central

    Krishna Reddy, Reddivari Chenna; Rasheed, Syed; Subba Rao, Devineni; Adam, Shaik; Raju, Chamarthi Naga

    2013-01-01

    A series of new 4-(5-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-2-carbonyl)-N-(substituted phenyl)piperazine-1-carboxamides 8(a–e)/carbothioamides 8(f–j) were accomplished for biological interest by the simple addition of active functionalized arylisocyanates 7(a–e)/arylisothiocyanates 7(f–j) with 2-isobutoxy-5-(4-methyl-2-(piperazine-1-carbonyl)thiazol-5-yl)benzonitrile (4). Compound 4 was synthesized in high yields (94%) by the condensation reaction of febuxostat (1) with piperazine using a selective reagent such as propylphosphonic anhydride (T3P). Antiviral activity against Tobacco mosaic virus (TMV) and antimicrobial activity of the synthesized compounds were evaluated. Biological data revealed that 4-nitrophenyl substituted urea 8d, and 3-bromophenyl substituted thiourea 8f exhibited promising antiviral activities. Moreover, 4-fluorophenyl substituted urea 8a, 4-nitrophenyl substituted urea 8d, 3-bromophenyl substituted thiourea 8f, and 2,4-dichlorophenyl substituted thiourea 8j exhibited potent antimicrobial activity. PMID:24453889

  9. New urea and thiourea derivatives of piperazine doped with febuxostat: synthesis and evaluation of anti-TMV and antimicrobial activities.

    PubMed

    Krishna Reddy, Reddivari Chenna; Rasheed, Syed; Subba Rao, Devineni; Adam, Shaik; Venkata Rami Reddy, Yellala; Raju, Chamarthi Naga

    2013-01-01

    A series of new 4-(5-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-2-carbonyl)-N-(substituted phenyl)piperazine-1-carboxamides 8(a-e)/carbothioamides 8(f-j) were accomplished for biological interest by the simple addition of active functionalized arylisocyanates 7(a-e)/arylisothiocyanates 7(f-j) with 2-isobutoxy-5-(4-methyl-2-(piperazine-1-carbonyl)thiazol-5-yl)benzonitrile (4). Compound 4 was synthesized in high yields (94%) by the condensation reaction of febuxostat (1) with piperazine using a selective reagent such as propylphosphonic anhydride (T3P). Antiviral activity against Tobacco mosaic virus (TMV) and antimicrobial activity of the synthesized compounds were evaluated. Biological data revealed that 4-nitrophenyl substituted urea 8d, and 3-bromophenyl substituted thiourea 8f exhibited promising antiviral activities. Moreover, 4-fluorophenyl substituted urea 8a, 4-nitrophenyl substituted urea 8d, 3-bromophenyl substituted thiourea 8f, and 2,4-dichlorophenyl substituted thiourea 8j exhibited potent antimicrobial activity. PMID:24453889

  10. Piperazine derivatives inhibit PrP/PrP(res) propagation in vitro and in vivo.

    PubMed

    Leidel, Fabienne; Eiden, Martin; Geissen, Markus; Hirschberger, Thomas; Tavan, Paul; Giese, Armin; Kretzschmar, Hans A; Schätzl, Hermann; Groschup, Martin H

    2014-02-28

    Prion diseases are fatal neurodegenerative disorders, which are not curable and no effective treatment exists so far. The major neuropathological change in diseased brains is the conversion of the normal cellular form of the prion protein PrPc(C) into a disease-associated isoform PrP(Sc). PrP(Sc) accumulates into multimeres and fibrillar aggregates, which leads to the formation of amyloid plaques. Increasing evidence indicates a fundamental role of PrP(Sc) species and its aggregation in the pathogenesis of prion diseases, which initiates the pathological cascade and leads to neurodegeneration accompanied by spongiform changes. In search of compounds that have the potential to interfere with PrP(Sc) formation and propagation, we used a cell based assay for the screening of potential aggregation inhibitors. The assay deals with a permanently prion infected cell line that was adapted for a high-throughput screening of a compound library composed of 10,000 compounds (DIVERset 2, ChemBridge). We could detect six different classes of highly potent inhibitors of PrP(Sc) propagation in vitro and identified piperazine derivatives as a new inhibitory lead structure, which increased incubation time of scrapie infected mice. PMID:24502948

  11. Dimethyl phenyl piperazine iodide (DMPP) induces glioma regression by inhibiting angiogenesis.

    PubMed

    He, Yan-Qing; Li, Yan; Wang, Xiao-Yu; He, Xiao-Dong; Jun, Li; Chuai, Manli; Lee, Kenneth Ka Ho; Wang, Ju; Wang, Li-Jing; Yang, Xuesong

    2014-01-15

    1,1-Dimethyl-4-phenyl piperazine iodide (DMPP) is a synthetic nicotinic acetylcholine receptor (nAChR) agonist that could reduce airway inflammation. In this study, we demonstrated that DMPP could dramatically inhibit glioma size maintained on the chick embryonic chorioallantoic membrane (CAM). We first performed MTT and BrdU incorporation experiments on U87 glioma cells in vitro to understand the mechanism involved. We established that DMPP did not significantly affect U87 cell proliferation and survival. We speculated that DMPP directly caused the tumor to regress by affecting the vasculature in and around the implanted tumor on our chick CAM model. Hence, we conducted detailed analysis of DMPP's inhibitory effects on angiogenesis. Three vasculogenesis and angiogenesis in vivo models were used in the study which included (1) early chick blood islands formation, (2) chick yolk-sac membrane (YSW) and (3) CAM models. The results revealed that DMPP directly suppressed all developmental stages involved in vasculogenesis and angiogenesis - possibly by acting through Ang-1 and HIF-2? signaling. In sum, our results show that DMPP could induce glioma regression grown on CAM by inhibiting vasculogenesis and angiogenesis. PMID:24162003

  12. Host\\/guest complex of ?-cyclodextrin\\/5-thia pentacene-14-one for photoinitiated polymerization of acrylamide in water

    Microsoft Academic Search

    Demet Karaca Balta; Nergis Arsu

    2008-01-01

    ?-Cyclodextrin (?-CD) was used to complex the photoinitiator, 5-thia pentacene-14-one (TX-A), yielding a water-soluble host\\/guest complex. IR, UV–Vis and fluorescence spectroscopy were employed to characterize complexed ?-CD\\/TX-A. Photoinitiated polymerization of acrylamide in water was achieved with ?-CD\\/TX-A in the presence of N-methyldiethanolamine (MDEA). Excellent polymerization yields were observed in air saturated solutions when MDEA was added.

  13. Control of water molecule aggregations in copper 1,4-cyclohexanedicarboxylate coordination polymers containing pyridyl-piperazine type ligands

    NASA Astrophysics Data System (ADS)

    Qiblawi, Sultan H.; LaDuca, Robert L.

    2014-01-01

    A series of layered divalent copper coordination polymers containing 1,4-cyclohexanedicarboxylate and long-spanning pyridyl-piperazine type ligands exhibits greatly different co-crystallized water molecule aggregations depending on the specific ligands used. Both [Cu(t-14cdc)(4-bpmp)]n (1, t-14cdc = trans-1,4-cyclohexanedicarboxylate, 4-bpmp = bis(4-pyridylmethyl)piperazine) and {[Cu(t-14cdc)(4-bpfp)(H2O)2]·6H2O}n (2, 4-bpfp = bis(4-pyridylformyl)piperazine) possess 2D (4,4) coordination polymer grids. However 1 lacks any co-crystallized water and has pinched grid apertures, while 2 manifests infinite water tapes with T6(2)4(2) classification and rectangular grid apertures. {[Cu2(c-14cdc)2(4-bpmp)]·2H2O}n (3, c-14cdc = cis-1,4-cyclohexanedicarboxylate) has [Cu2(c-14cdc)]2 ribbons with paddlewheel dimeric units linked into 2D slabs by 4-bpmp tethers, along with isolated water molecule pairs. In contrast, {[Cu2(c-14cdc)2(4-bpfp)]·10H2O}n (4) shows a very similar underlying coordination polymer topology but entrains unique decameric water molecule clusters. The minor product {[Cu2(c-14cdcH)2(t-1,4-cdc)(4-bpfp)2(H2O)2]·2H2O}n (5) was isolated along with 4; this compound underwent some in situ cis to trans cyclohexane-dicarboxylate ligand isomerization and exhibits a ladder polymer motif.

  14. Synthesis of New N,N’-Bis(5-arylidene-4-oxo-4,5-dihydrothiazolin-2-yl)piperazine Derivatives Under Microwave Irradiation and Preliminary Biological Evaluation

    PubMed Central

    Coulibaly, Wacothon Karime; Paquin, Ludovic; Bénié, Anoubilé; Bekro, Yves-Alain; Durieux, Emilie; Meijer, Laurent; Le Guével, Rémy; Corlu, Anne; Bazureau, Jean-Pierre

    2012-01-01

    New N,N’-bis(5-arylidene-4-oxo-4,5-dihydrothiazoline-2-yl)diamine derivatives 5 were prepared in two steps from rhodanine and piperazine, or 1,4-bis(3-amino-propyl)piperazine, under microwave reaction conditions with retention of configuration. Some of these compounds were tested for in vitro antiproliferative activities and for their kinase inhibitory potencies towards six kinases (CDK5/p25, GSK3?/?, DYRK1A, DYRK2, CLK1, and CLK2). The compound 5d showed nanomolar activity towards DYRK1A kinase (IC50 = 0.041 ?M). PMID:23264934

  15. Synthesis and structure–activity relationships of indole and benzimidazole piperazines as histamine H 4 receptor antagonists

    Microsoft Academic Search

    Nalan Terzioglu; Richard M. van Rijn; Remko A. Bakker; Iwan J. P. De Esch; Rob Leurs

    2004-01-01

    We describe the structure–activity relationships for a series of ligands structurally related to the recently identified (5-chloro-1H-indol-2-yl)-(4-methyl-piperazin-1-yl)-methanone (1) as histamine H4 receptor (H4R) antagonists. Furthermore, we identified related benzimidazoles as novel lead compounds for the H4R. The ligands have been evaluated by radioligand displacement studies and functional assays for their interaction with both the human histamine H3 and H4 receptors

  16. Protective effects of a piperazine derivative [N-{4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-phenyl} carbamic acid ethyl ester] against aluminium-induced neurotoxicity: insights from in silico and in vivo studies.

    PubMed

    Meena, Poonam; Manral, Apra; Saini, Vikas; Tiwari, Manisha

    2015-04-01

    The cholinergic hypothesis associated with Alzheimer's disease has spurred the development of numerous structural classes of compounds with different pharmacological profiles aimed at increasing central cholinergic neurotransmission. In the present study, six synthetic piperazine derivatives D1-D6 were screened for their efficacy as acetylcholinesterase inhibitors (AChEIs) through in silico and in vitro studies. Compound D2 was found to be a potential AChEI with adequate pharmacokinetic properties, as supported by in silico study. Further, in vivo studies were designed to examine the protective effect of piperazine derivative D2 (3 and 5 mg/kg for 6 weeks) in ameliorating the alterations induced by aluminium chloride (AlCl(3)) on behavioural and neurochemical indices. Behavioural tests (Morris water maze and elevated plus maze) revealed significant alterations in the short-term memory and anxiety levels in rats treated with AlCl(3), which was further improved after D2 treatment. Further, D2 treatment attenuated the neurotoxic effects of AlCl(3) as shown by the improvement in rats performance in Water maze test and in lowering AChE activity. Besides preventing lipid peroxidation and protein damage, changes in the levels of endogenous antioxidant enzymes (GST, GPx, GR and GSH) associated with AlCl3 administration were also restored upon treatment with D2. Thus, our results support the neuroprotective potential of compound D2, thus validating its use in alleviating toxic effects of aluminium. PMID:25403519

  17. Piperazine and its carboxylic acid derivatives-functionalized mesoporous silica as nanocarriers for gemcitabine: adsorption and release study.

    PubMed

    Bahrami, Zohreh; Badiei, Alireza; Atyabi, Fatemeh; Darabi, Hossein Reza; Mehravi, Bita

    2015-04-01

    Piperazine-functionalized SBA-15 nanorods were synthesized by post grafting method with methyldimethoxysilylpropylpiperazine (MDSP). The carboxylic acid derivatives of piperazine-functionalized SBA-15 nanorods were obtained using two different kinds of precursors (bromoacetic acid and succinic anhydride). The prepared materials were used as nanocarriers for the anticancer drug (gemcitabine). The obtained samples were characterized by SAXS, N2 adsorption-desorption, SEM, TEM, DLS, thermogravimetric analysis, FTIR, Raman and UV spectroscopies. The adsorption and release properties of all samples were investigated. In vitro study included cell toxicity. It was found that the surface functionalization increases the interaction between the carrier and gemcitabine and results in the loading enhancement of the drug. In addition, the adsorption of gemcitabine on the modified mesoporous matrix depends on the type of the introduced functional groups. The carboxylic acid-modified samples have higher loading content, due to the strong interaction with gemcitabine. The maximum content of deposited drug in the modified SBA-15 nanorods is close to 36wt.% that it is related to PC2-SBA-15 sample which obtained using succinic anhydride. The obtained results reveal that the surface functionalization leads toward a significant decrease of the drug release rate without any appreciable cytotoxicity. No significant differences are observed among the drug release rate from the modified samples. PMID:25686928

  18. Piperazine derivatives: synthesis, inhibition of the Mycobacterium tuberculosis enoyl-acyl carrier protein reductase and SAR studies.

    PubMed

    Rotta, Mariane; Pissinate, Kenia; Villela, Anne Drumond; Back, Davi Fernando; Timmers, Luis Fernando Saraiva Macedo; Bachega, José Fernando Ruggiero; de Souza, Osmar Norberto; Santos, Diógenes Santiago; Basso, Luiz Augusto; Machado, Pablo

    2015-01-27

    The Mycobacterium tuberculosis NADH-dependent enoyl-acyl carrier protein reductase (MtInhA) catalyzes hydride transfer to long-chain enoyl thioester substrates. MtInhA is a member of the mycobacterial type II dissociated fatty acid biosynthesis system, and is the bona fide target for isoniazid, the most prescribed drug for tuberculosis treatment. Here, a series of piperazine derivatives was synthesized and screened as MtInhA inhibitors, which resulted in the identification of compounds with IC50 values in the submicromolar range. A structure-activity relationship (SAR) evaluation indicated the importance of the chemical environment surrounding the carbonyl group for inhibition. In addition, the structure of one selected compound was supported by crystallographic studies, and experimental geometrical values were compared with semi-empirical quantum chemical calculations. Furthermore, the mode of inhibition and inhibitory dissociation constants were determined for the nine most active compounds. These findings suggest that these 9H-fluoren-9-yl-piperazine-containing compounds interact with MtInhA at the enoyl thioester (2-trans-dodecenoyl-CoA) substrate binding site. PMID:25461892

  19. Temperature- and pH-responsive nanoparticles of biocompatible polyurethanes for doxorubicin delivery.

    PubMed

    Wang, Anning; Gao, Hui; Sun, Yanfang; Sun, Yu-long; Yang, Ying-Wei; Wu, Guolin; Wang, Yinong; Fan, Yunge; Ma, Jianbiao

    2013-01-30

    A series of temperature- and pH-responsive polyurethanes based on hexamethylene diisocyanate (HDI) and 4,4'-diphenylmethane diisocyanate (MDI) were synthesized by a coupling reaction with bis-1,4-(hydroxyethyl) piperazine (HEP), N-methyldiethanolamine (MDEA) and N-butyldiethanolamine (BDEA), respectively. The chemical structure, molecular weight, thermal property and crystallization properties were characterized by Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) spectroscopy. The resulting polyurethanes were then used to prepare nanoparticles either by direct dispersion method or dialysis method. Their pH and temperature responsibilities were evaluated by optical transmittance and size measurement in aqueous media. Interestingly, HDI-based and MDI-based polyurethanes exhibited different pH and temperature responsive properties. Nanoparticles based on HDI-HEP and HDI-MDEA were temperature-responsive, while MDI-based biomaterials were not. All of them showed pH-sensitive behavior. The possible responsive mechanism was investigated by (1)H NMR spectroscopy. The cytotoxicity of the polyurethanes was evaluated using methylthiazoletetrazolium (MTT) assay in vitro. It was shown that the HDI-based polyurethanes were non-toxic, and could be applied to doxorubicin (DOX) encapsulation. The experimental results indicated that DOX could be efficiently encapsulated into polyurethane nanoparticles and uptaken by Huh-7 cells. The loaded DOX molecules could be released from the drug-loaded polyurethane nanoparticles upon pH and temperature changes, responsively. PMID:23262421

  20. HEAT OF DISSOLUTION MEASUREMENTS FOR CO2 IN MIXED ALKANOLAMINE SOLVENTS

    SciTech Connect

    Vinayak N. Kabadi

    2005-05-23

    The main objective of this project is to measure heat of dissolution of CO{sub 2} in carefully selected mixed alkanolamine solvent systems, and provide such directly measured data that might be used for efficient design of CO{sub 2} capture processes, or for better understanding of thermodynamics of CO{sub 2}-alkanolamine systems. Carbon dioxide is one of the major greenhouse gases, and the need for stabilization of its composition in earth's atmosphere is vital for the future of mankind. Although technologies are available for capture and storage of CO{sub 2}, these technologies are far too expensive for economical commercialization. Reduction of cost would require research for refinement of the technology. For more economical CO{sub 2} capture and regeneration, there is a need for development of more efficient solvent systems. In this project we will extend the thermodynamic database by measuring heat of solution data of CO{sub 2} in mixed solvents made of MEA (monoethanolamine), MDEA (methyldiethanolamine), piperazine, and water. Mixed solvents of different compositions will be selected and in each case data will be measured at temperatures 40 and 80C and various partial pressures of CO{sub 2}. At the end of the project, observations, conclusions, and recommendations will be derived for the choice of mixed solvents for efficient CO{sub 2} capture with potential for commercialization.

  1. Preferences of rhodamine coupled (aminoalkyl)-piperazine probes towards Hg(II) ion and their FRET mediated signaling.

    PubMed

    Biswal, Biswonath; Bag, Bamaprasad

    2013-08-14

    The metal ion induced absorption and emission signaling pattern of rhodamine coupled bis-(aminopropyl)-piperazine (1-3) and (aminoethyl)-piperazine (4) based probes evaluated in MeCN as well as in an MeCN-H2O binary mixture medium revealed that these probes exhibit optical signaling perturbations to a varying extent in MeCN, however, their complexation induced signaling could be tuned selectively towards Hg(II) in the presence of an aqueous component in the solvent medium where competitive interactions such as metal-probe interactions and hydration of metal ions play the determining factor to induce aqueous promoted Hg(II) selectivity. Attachment of another fluorophore (anthracene and nitrobenzofurazan moieties in 2 and 3 respectively) at the other end of the rhodamine coupled bis-(aminopropyl)-piperazine receptor enabled these probes to facilitate a complexation induced fluorescence resonance energy transfer (FRET) from the excited fluorophore to the ring-opened rhodamine along with contributions through operative PET inhibition and rhodamine delactonization processes. The enhancement in absorption transition of these probes at ~557 nm upon selective Hg(II)-complexation and consequent colourless to pink colour change in the solution imply a chromogenic signaling pattern whereas simultaneous fluorescence amplification and/or FRET initiation lead to fluorogenic signaling to facilitate detection at lower concentration. The Hg(II)-selective photo-physical spectral modulation in the presence of other competitive metal ions, and their reversible dual channel signaling pattern under the action of counter anions or chelating agents such as EDTA or ethylenediamine establish the potential of these probes for highly selective, sensitive and reversible 'OFF-ON-OFF' detection of Hg(II). The complexation induced optical signaling pattern of probes with a propyl-linker in their receptor (1-3) in comparison with that of 4 consisting of an ethyl-spacer indicate that signaling probe design with a substituted 'aminoalkyl-lactonized-rhodamine' subunit preferentially exhibit Hg(II) selective and sensitive dual mode signaling in an organic-aqueous mixture medium irrespective of carbon-length of the flexible alkyl spacer. PMID:23783407

  2. Enhanced mechanical properties of linear segmented shape memory poly(urethane-urea) by incorporating flexible PEG400 and rigid piperazine

    NASA Astrophysics Data System (ADS)

    Zhang, Xiao-Yan; Ma, Yu-Fei; Li, Yong-Gang; Wang, Pin-Pin; Wang, Yuan-Liang; Luo, Yan-Feng

    2012-12-01

    The goal of this study is to design and synthesize a linear segmented shape memory poly(urethane-urea) (SMPUU) that possesses near-body-temperature shape memory temperature ( T tran) and enhanced mechanical properties by incorporating flexible poly(ethylene glycol) 400 (PEG400) to form poly(D,L-lactic acid)-based macrodiols (PDLLA-PEG400-PDLLA) and then rigid piperazine (PPZ) as a chain extender to form the desired SMPUUs (PEG400-PUU-PPZ). PEG400 increased M n while maintaining a lower T g of PDLLA-PEG400-PDLLA, which together with PPZ improved the mechanical properties of PEG400-PUU-PPZ. The obtained optimum SMPUU with enhanced mechanical properties ( ? y = 24.28 MPa; ? f = 698%; U f = 181.5 MJ/m3) and a T g of 40.62°C exhibited sound shape memory properties as well, suggesting a promising SMPUU for in vivo biomedical applications.

  3. Acid gas treating by aqueous alkanolamines. Annual report, January-December 1994

    SciTech Connect

    Sandall, O.C.; Rinker, E.B.; Ashour, S.

    1994-12-01

    The objective of this work is to investigate the simulateneous absorption or desorption of CO2 and H2S into and from a mixed aqueous amine solvent consisting of methyldiethanolamine (MDEA) and diethanolamine (DEA). In work completed this year the authors have measured the density, viscosity and surface tension of pure MDEA and DEA over a range in temperatures. The diffusivity of N2O was measured in aqueous blends of MDEA and DEA at 50 wt% total amine for various ratios of DEA to MDEA over the temperature range 20 to 80 deg. C. A theoretically-based model has been developed for the correlation of the physical solubility of N2O in aqueous amine solutions. A penetration theory type model which was developed to describe acid gas absorption in aqueous amine solutions was used to carry out a sensitivity analysis for the various parameters affecting the rate of absorption of CO2 in MDEA solutions.

  4. Second generation N-(1,2-diphenylethyl)piperazines as dual serotonin and noradrenaline reuptake inhibitors: improving metabolic stability and reducing ion channel activity.

    PubMed

    Fray, M Jonathan; Fish, Paul V; Allan, Gillian A; Bish, Gerwyn; Clarke, Nick; Eccles, Rachel; Harrison, Anthony C; Le Net, Jean-Loic; Phillips, Stephen C; Regan, Nicola; Sobry, Cecile; Stobie, Alan; Wakenhut, Florian; Westbrook, Dominique; Westbrook, Simon L; Whitlock, Gavin A

    2010-06-15

    New N-(1,2-diphenylethyl)piperazines 6 are disclosed as dual serotonin and noradrenaline reuptake inhibitors (SNRI) which may have potential in treating stress urinary incontinence (SUI). In this Letter, we present new data for SNRI PF-526014 (4) including performance in a canine in vivo model of SUI, cardiovascular assessment, pharmacokinetics in dog and determination of the primary routes of metabolism in vitro. Starting from 4, detailed structure activity relationships established that potent dual SNRIs could be achieved by appropriate substitution of the phenyl rings (6: R; R(1)) combined with a preferred stereochemistry. From this set of compounds, piperazine (-)-6a was identified as a potent and selective dual SNRI with improved metabolic stability and reduced ion channel activity when compared to 4. Based on this profile, (-)-6a was selected for further evaluation in a preclinical model of SUI. PMID:20471260

  5. ANALYTICAL METHOD FOR 1METHYL4-AMINO-PIPERAZINE IN AN ACTIVE PHARMACEUTICAL INGREDIENT USING CHEMICAL DERIVATIZATION AND HPLC-UV

    Microsoft Academic Search

    Jyoti Patel; Eric Loeser; Rudy Kircher; Hanumantha Rao Marrepalli; Steven Fazio; Donald Drinkwater; Patrick Drumm

    2010-01-01

    A method to form a UV-active derivative of 1-methyl-4-amino-piperazine (AMP) was developed. The method was based on the reaction of AMP with benzaldehyde, forming a stable derivative, which was UV-active. The method was used to analyze samples of an active pharmaceutical ingredient (API) for trace amounts of AMP. The derivatization approach allowed detection of AMP at low levels, using readily

  6. Piperazine derivatives including the putative anxiolytic drugs, buspirone and ipsapirone, are agonists at 5-HT1A receptors negatively coupled with adenylate cyclase in hippocampal neurons.

    PubMed

    Bockaert, J; Dumuis, A; Bouhelal, R; Sebben, M; Cory, R N

    1987-05-01

    Two putative anxiolytic drugs [ipsapirone (TVXQ 7821) and buspirone], structurally unrelated to benzodiazepines, have negligible ataxic and sedative side effects. These drugs are piperazine analogs which interact at 5-HT1 binding sites. It is demonstrated here that these drugs and two other piperazine derivatives, trifluoromethylphenylpiperazine (TFMPP) and m-chlorophenylpiperazine (mCPP), are agonists at 5-HT1A receptors, a subclass of the 5-HT1 receptor, mediating inhibition of forskolin (100 microM) stimulated adenylate cyclase in particulate fractions of guinea pig hippocampus as well as inhibition of the formation of cyclic AMP promoted by vasoactive intestinal polypeptide (0.1 microM) plus forskolin (1 microM) in mouse hippocampal neurons in primary culture. This study demonstrates that these piperazine based drugs act in both brain homogenate preparations and in intact neurons in a similar manner. The biochemical models described here may aid in the development of even more active drugs in this class. PMID:2886925

  7. Structure-based design, synthesis and biological testing of piperazine-linked bis-epipodophyllotoxin etoposide analogs.

    PubMed

    Yadav, Arun A; Chee, Gaik-Lean; Wu, Xing; Patel, Daywin; Yalowich, Jack C; Hasinoff, Brian B

    2015-07-01

    Drugs that target DNA topoisomerase II, such as the epipodophyllotoxin etoposide, are a clinically important class of anticancer agents. A recently published X-ray structure of a ternary complex of etoposide, cleaved DNA and topoisomerase II? showed that the two intercalated etoposide molecules in the complex were separated by four DNA base pairs. Thus, using a structure-based design approach, a series of bis-epipodophyllotoxin etoposide analogs with piperazine-containing linkers was designed to simultaneously bind to these two sites. It was hypothesized that two-site binding would produce a more stable cleavage complex, and a more potent anticancer drug. The most potent bis-epipodophyllotoxin, which was 10-fold more growth inhibitory toward human erythroleukemic K562 cells than etoposide, contained a linker with eight methylene groups. All of the mono- and bis-epipodophyllotoxins, in a variety of assays, showed strong evidence that they targeted topoisomerase II. COMPARE analysis of NCI 60-cell GI50 endpoint data was also consistent with these compounds targeting topoisomerase II. PMID:25922181

  8. Piperazine-2,3-dicarboxylic acid Derivatives as Dual Antagonists of NMDA and GluK1-Containing Kainate Receptors

    PubMed Central

    Irvine, Mark W.; Costa, Blaise M.; Dlaboga, Daniel; Culley, Georgia; Hulse, Richard; Scholefield, Caroline L.; Atlason, Palmi; Fang, Guangyu; Eaves, Richard; Morley, Richard; Mayo-Martin, Maria B.; Amici, Mascia; Bortolotto, Zuner A.; Donaldson, Lucy; Collingridge, Graham L.; Molnár, Elek; Monaghan, Daniel T.; Jane, David E.

    2011-01-01

    Competitive N-methyl-D-aspartate receptor (NMDAR) antagonists bind to the GluN2 subunit, of which there are four types (GluN2A-D). We report that some N1-substituted derivatives of cis-piperazine-2,3-dicarboxylic acid display improved relative affinity for GluN2C and GluN2D versus GluN2A and GluN2B. These derivatives also display subtype-selectivity among the more distantly related kainate receptor family. Compounds 18i and (?)-4 were the most potent kainate receptor antagonists and 18i was selective for GluK1 versus GluK2, GluK3 and AMPA receptors. Modeling studies revealed structural features required for activity at GluK1 subunits and suggested that S674 was vital for antagonist activity. Consistent with this hypothesis, replacing the equivalent residue in GluK3 (alanine) with a serine imparts 18i antagonist activity. Antagonists with dual GluN2D and GluK1 antagonist activity may have beneficial effects in various neurological disorders. Consistent with this idea, antagonist 18i (30 mg/Kg i.p.) showed antinociceptive effects in an animal model of mild nerve injury. PMID:22111545

  9. N-Aryl Piperazine Metabotropic Glutamate Receptor 5 Positive Allosteric Modulators Possess Efficacy in Preclinical Models of NMDA Hypofunction and Cognitive Enhancement

    PubMed Central

    Gregory, K.J.; Herman, E.J.; Ramsey, A.J.; Hammond, A.S.; Byun, N.E.; Stauffer, S.R.; Manka, J.T.; Jadhav, S.; Bridges, T.M.; Weaver, C.D.; Niswender, C.M.; Steckler, T.; Drinkenburg, W.H.; Ahnaou, A.; Lavreysen, H.; Macdonald, G.J.; Bartolomé, J.M.; Mackie, C.; Hrupka, B.J.; Caron, M.G.; Daigle, T.L.; Lindsley, C.W.; Conn, P.J.

    2013-01-01

    Impaired transmission through glutamatergic circuits has been postulated to play a role in the underlying pathophysiology of schizophrenia. Furthermore, inhibition of the N-methyl-d-aspartate (NMDA) subtype of ionotropic glutamate receptors (NMDAR) induces a syndrome that recapitulates many of the symptoms observed in patients with schizophrenia. Selective activation of metabotropic glutamate receptor subtype 5 (mGlu5) may provide a novel therapeutic approach for treatment of symptoms associated with schizophrenia through facilitation of transmission through central glutamatergic circuits. Here, we describe the characterization of two novel N-aryl piperazine mGlu5 positive allosteric modulators (PAMs): 2-(4-(2-(benzyloxy)acetyl)piperazin-1-yl)benzonitrile (VU0364289) and 1-(4-(2,4-difluorophenyl)piperazin-1-yl)-2-((4-fluorobenzyl)oxy)ethanone (DPFE). VU0364289 and DPFE induced robust leftward shifts in the glutamate concentration-response curves for Ca2+ mobilization and extracellular signal-regulated kinases 1 and 2 phosphorylation. Both PAMs displayed micromolar affinity for the common mGlu5 allosteric binding site and high selectivity for mGlu5. VU0364289 and DPFE possessed suitable pharmacokinetic properties for dosing in vivo and produced robust dose-related effects in reversing amphetamine-induced hyperlocomotion, a preclinical model predictive of antipsychotic-like activity. In addition, DPFE enhanced acquisition of contextual fear conditioning in rats and reversed behavioral deficits in a mouse model of NMDAR hypofunction. In contrast, DPFE had no effect on reversing apomorphine-induced disruptions of prepulse inhibition of the acoustic startle reflex. These mGlu5 PAMs also increased monoamine levels in the prefrontal cortex, enhanced performance in a hippocampal-mediated memory task, and elicited changes in electroencephalogram dynamics commensurate with procognitive effects. Collectively, these data support and extend the role for the development of novel mGlu5 PAMs for the treatment of psychosis and cognitive deficits observed in individuals with schizophrenia. PMID:23965381

  10. 3-(Adamantan-1-yl)-4-phenyl-1-[(4-phenyl­piperazin-1-yl)meth­yl]-1H-1,2,4-triazole-5(4H)-thione

    PubMed Central

    Al-Abdullah, Ebtehal S.; Asiri, Hanadi H.; El-Emam, Ali; Ng, Seik Weng

    2012-01-01

    The title mol­ecule, C29H35N5S, displays a chair-shaped piperazine ring, as well as an approximately planar triazole ring (r.m.s. deviation = 0.001?Å) whose phenyl substituent is nearly perpendicular to the mean plane of the five-membered ring [dihedral angle = 88.9?(1)°]. The substituents on the piperazine ring occupy equatorial sites. In the crystal, the adamantyl cage is disordered over two sets of sites with a major component of 67.8?(5)%. Weak inter­molecular C—H?S hydrogen bonding is present in the crystal. PMID:22346974

  11. Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors: SAR of a series of 3-[6-(4-substituted-piperazin-1-yl)-4-methyl-1 H-benzimidazol-2-yl]-1 H-pyridine-2-one

    Microsoft Academic Search

    Upender Velaparthi; Mark G. Saulnier; Mark D. Wittman; Peiying Liu; David B. Frennesson; Kurt Zimmermann; Joan M. Carboni; Marco Gottardis; Aixin Li; Ann Greer; Wendy Clarke; Zheng Yang; Krista Menard; Francis Y. Lee; George Trainor; Dolatrai Vyas

    2010-01-01

    A series of 3-[6-(4-substitued-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one were synthesized to modulate CYP3A4 inhibition and improve aqueous solubility of our prototypical compound BMS-536924 (1), while maintaining potent IGF-1R inhibitory activity. Structure–activity and structure–solubility studies led to the identification of BMS-577098 (27), which demonstrates oral in vivo efficacy in animal models. The improvement was achieved by replacing morpholine with more polar bio-isoster piperazine and modulating

  12. Synthesis of N-substituted- N-acylthioureas of 4-substituted piperazines endowed with local anaesthetic, antihyperlipidemic, antiproliferative activities and antiarrythmic, analgesic, antiaggregating actions

    Microsoft Academic Search

    Angelo Ranise; Andrea Spallarossa; Olga Bruno; Silvia Schenone; Paola Fossa; Giulia Menozzi; Francesco Bondavalli; Luisa Mosti; Annalisa Capuano; Filomena Mazzeo; Giuseppe Falcone; Walter Filippelli

    2003-01-01

    Three series of N-acyl and N-cyclohexyl- or N-methyl or N-phenyl-thioureas of 4-substituted (methyl, phenyl, 2-pyridyl)piperazines (4–12) were synthesised according to a highly convergent one-pot procedure and tested in vivo (local anaesthetic, anti-hyperlipoproteinemic, analgesic, anti-inflammatory, antiarrythmic activities) and in vitro (antiaggregating and, for some selected derivatives, antiproliferative activities) experiments. All the test compounds showed local anaesthesia in particular 4Ar4, 5Ar4, 12Ar3

  13. Nippostrongylus brasiliensis infection in the rat: effect of iron and protein deficiency on the anthelmintic efficacy of mebendazole, pyrantel, piperazine, and levamisole.

    PubMed Central

    Duncombe, V M; Bolin, T D; Davis, A E; Fagan, M R; Kelly, J D

    1979-01-01

    The benzimidazole anthelmintics mebendazole and fenbendazole have been shown to be much less effective against Nippostrongylus brasiliensis infections in the rat on a combined iron and protein deficient diet. In the present experiments it was shown that the anthelmintic efficacy of mebendazole was significantly impaired in the rat on either an iron deficient or a protein deficient diet. Furthermore, iron and protein deficiency reduced the efficacy of the anthelmintics pyrantel and piperazine but not levamisole. The finding that nutritional deficiencies reduce anthelmintic efficacy may well be relevant to worm eradication programmes in iron deficient and protein calorie malnourished populations. PMID:447110

  14. Synthesis and anticancer activities of 4-(4-substituted piperazin)-5,6,7-trialkoxy quinazoline derivatives.

    PubMed

    Zhang, Ying; Huang, Yin-Jiu; Xiang, Hong-Mei; Wang, Pei-Yi; Hu, De-Yu; Xue, Wei; Song, Bao-An; Yang, Song

    2014-05-01

    A series of 4-(4-substituted piperazin)-5,6,7-trialkoxy quinazoline was prepared by conventional heating methods. Among these compounds, the crystal structure of compound 10o (CCDC: 916922) was determined by X-ray crystallography. Bioassay results showed that most target compounds had certain inhibition activities against proliferation of tumor cells, and some compounds even had good broad-spectrum inhibition activities. The ethoxyl series of compounds possessed higher inhibition activities against tumor cells than the methoxyl series of compounds. Bioactivity tests showed that the IC50 values of compound 10s against PC3, MGC803, A375, and A549 cells were 1.8, 2.8, 1.3, and 2.9 ??, respectively, which were much higher than those of commercial gefitinib (7.2, 7.6, 7.2, and 9.8 ?M, respectively). Conversely, the IC50 values of compound 10s were very low against NH3T3, indicating only weak effect on normal cells as also proven by lactate dehydrogenase and acridine orange/ethidium bromide staining. Analyses of cell configuration and cell cycle revealed that compound 10s possibly caused cells to remain at G0/G1 phase by inhibiting cell proliferation for 24 h. Compound 10s also inhibited the phosphorylation of ERK1/2 and P38 with obvious concentration dependence. Thus, these compounds can inhibit the proliferation of A549 cells through the interruption of ERK1/2 and P38signaling pathways. PMID:24675177

  15. Crystal structure of catena-poly[[[tetra-aqua-zinc(II)]-?-1,4-bis-[4-(1H-imidazol-1-yl)benzo-yl]piperazine] dinitrate monohydrate].

    PubMed

    Hou, Chen; Gan, Hong-Mei; Liu, Jia-Cheng

    2015-05-01

    In the title polymeric complex, {[Zn(C24H22N6O2)(H2O)4](NO3)2·2H2O} n , the Zn(II) cation, located about a twofold rotation axis, is coordinated by two imidazole groups and four water mol-ecules in a distorted N2O4 octa-hedral geometry; among the four coordinate water mol-ecules, two are located on the same twofold rotation axis. The 1,4-bis-[4-(1H-imidazol-1-yl)benzo-yl]piperazine] ligand is centro-symmetric, with the centroid of the piperazine ring located on an inversion center, and bridges the Zn(II) cations, forming polymeric chains propagating along [201]. In the crystal, O-H?O and weak C-H?O hydrogen bonds link the polymeric chains, nitrate anions and solvent water mol-ecules into a three-dimensional supra-molecular architecture. A short O?O contact of 2.823?(13)?Å is observed between neighboring nitrate anions. PMID:25995894

  16. Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines.

    PubMed

    Rosenbaum, Christopher D; Carreiro, Stephanie P; Babu, Kavita M

    2012-03-01

    Despite their widespread Internet availability and use, many of the new drugs of abuse remain unfamiliar to health care providers. The herbal marijuana alternatives, like K2 or Spice, are a group of herbal blends that contain a mixture of plant matter in addition to chemical grade synthetic cannabinoids. The synthetic cathinones, commonly called "bath salts," have resulted in nationwide emergency department visits for severe agitation, sympathomimetic toxicity, and death. Kratom, a plant product derived from Mitragyna speciosa Korth, has opioid-like effects, and has been used for the treatment of chronic pain and amelioration of opioid-withdrawal symptoms. Salvia divinorum is a hallucinogen with unique pharmacology that has therapeutic potential but has been banned in many states due to concerns regarding its psychiatric effects. Methoxetamine has recently become available via the Internet and is marked as "legal ketamine." Moreover, the piperazine derivatives, a class of amphetamine-like compounds that includes BZP and TMFPP, are making a resurgence as "legal Ecstasy." These psychoactives are available via the Internet, frequently legal, and often perceived as safe by the public. Unfortunately, these drugs often have adverse effects, which range from minimal to life-threatening. Health care providers must be familiar with these important new classes of drugs. This paper discusses the background, pharmacology, clinical effects, detection, and management of synthetic cannabinoid, synthetic cathinone, methoxetamine, and piperazine exposures. PMID:22271566

  17. Amine-degradation products play no part in corrosion at gas-sweetening plants

    SciTech Connect

    Blanc, C.; Grall, M.; Demarais, G.

    1982-11-15

    Gas-sweetening units using diethanolamine (DEA) and methyldiethanolamine (MDEA) are occasionally subject to corrosion. Discounting the basic degradation products of DEA as the cause, researchers (1) confirmed the presence of formic, oxalic, and acetic acids in used amine solutions, (2) defined oxygen's role in forming these carboxylic acids, and (3) demonstrated that the acid contents of different units are about the same order of magnitude for both DEA and MDEA. In most cases, oxygen can be easily excluded from gas-treating units, especially in storage tanks, thereby limiting the formation of acid products.

  18. Toward understanding amines and their degradation products from postcombustion CO2 capture processes with aerosol mass spectrometry.

    PubMed

    Ge, Xinlei; Shaw, Stephanie L; Zhang, Qi

    2014-05-01

    Amine-based postcombustion CO2 capture (PCCC) is a promising technique for reducing CO2 emissions from fossil fuel burning plants. A concern of the technique, however, is the emission of amines and their degradation byproducts. To assess the environmental risk of this technique, standardized stack sampling and analytical methods are needed. Here we report on the development of an integrated approach that centers on the application of a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) for characterizing amines and PCCC-relevant species. Molecular characterization is achieved via ion chromatography (IC) and electrospray ionization high-resolution mass spectrometry (ESI-MS). The method has been optimized, particularly, by decreasing the AMS vaporizer temperature, to gain quantitative information on the elemental composition and major nitrogen-containing species in laboratory-degraded amine solvents commonly tested for PCCC applications, including ethanolamine (MEA), methyldiethanolamine (MDEA), and piperazine (PIP). The AMS-derived nitrogen-to-carbon (N/C) ratios for the degraded solvent and product mixtures agree well with the results from a total organic carbon and total nitrogen (TOC/TN) analyzer. In addition, marker ions identified in the AMS spectra are used to estimate the mass contributions of individual species. Overall, our results indicate that this new approach is suitable for characterizing PCCC-related mixtures as well as organic nitrogen species in other sample types. As an online instrument, AMS can be used for both real-time characterization of emissions from operating PCCC plants and ambient particles in the vicinity of the facilities. PMID:24617831

  19. Application of the Ugi reaction with multiple amino acid-derived components: synthesis and conformational evaluation of piperazine-based minimalist peptidomimetics.

    PubMed

    Stucchi, Mattia; Cairati, Silvia; Cetin-Atalay, Rengul; Christodoulou, Michael S; Grazioso, Giovanni; Pescitelli, Gennaro; Silvani, Alessandra; Yildirim, Deniz Cansen; Lesma, Giordano

    2015-04-22

    The concurrent employment of ?-amino acid-derived chiral components such as aldehydes and ?-isocyanoacetates, in a sequential Ugi reaction/cyclization two-step strategy, opens the door to the synthesis of three structurally distinct piperazine-based scaffolds, characterized by the presence of l-Ala and/or l-Phe-derived side chains and bearing appropriate functionalities to be easily applied in peptide chemistry. By means of computational studies, these scaffolds have been demonstrated to act as minimalist peptidomimetics, able to mimic a well defined range of peptide secondary structures and therefore potentially useful for the synthesis of small-molecule PPI modulators. Preliminary biological evaluation of two different resistant hepatocellular carcinoma cellular lines, for which differentiation versus resistance ability seem to be strongly correlated with well defined types of PPIs, has revealed a promising antiproliferative activity for selected compounds. PMID:25821154

  20. An annelated thioxanthone as a new Type II initiator

    Microsoft Academic Search

    Demet Karaca Balta; Nihal Cetiner; Gokhan Temel; Zuhal Turgut; Nergis Arsu

    2008-01-01

    5-Thia-naphthacen-12-one (TX-Np) was synthesized as a potential photoinitiator for radical polymerization. Polymerization studies revealed that TX-Np acts as a photoinitiator for radical polymerization of acrylic type monomers in the presence of N-methyldiethanolamine (MDEA). The phosphorescence spectrum measured at 77K in ethanol showed an emission band at ?max=505nm corresponding to the approximate triplet energy of ca. 237kJ\\/mol.The phosphorescence lifetime was found

  1. 2-Mercaptothioxanthone as a Novel Photoinitiator for Free Radical Polymerization

    Microsoft Academic Search

    Lerzan Cokbaglan; Nergis Arsu; Yusuf Yagci; Steffen Jockusch; Nicholas J. Turro

    2003-01-01

    Mercaptothioxanthone (TX-SH), a hydrogen abstraction type photoinitiator for free radical polymerization, is synthesized and characterized. Its capability to act as an initiator for the polymerization of methyl methacrylate (MMA), styrene (St), and multifunctional monomers is examined. The relative efficiencies of TX-SH, the parent thioxanthone (TX), and their combination with an amine synergist such as N-methyldiethanolamine (MDEA) are compared in the

  2. Gas permeability of cupric ion containing HTPB based polyurethane membranes

    Microsoft Academic Search

    Shih-Liang Huang; Ruoh-Chyu Ruaan; Juin-Yih Lai

    1997-01-01

    For the purpose of oxygen enrichment from air, the gas permeability and selectivity of an ionic polyurethane membrane was under investigation. Membranes of ionic polyurethane were prepared by step-growth polymerization of hydroxyl terminated polybutadiene (HTPB) and 4,4?-dicyclohexylmethane diisocyanate (H12MDI). The ionic group was introduced by adding N-methyldiethanolamine (MDEA) as the chain extender of which the tertiary amines were complexed with

  3. CFD simulation of natural gas sweetening in a gas–liquid hollow-fiber membrane contactor

    Microsoft Academic Search

    Mashallah Rezakazemi; Zahra Niazi; Mojtaba Mirfendereski; Saeed Shirazian; Toraj Mohammadi; Afshin Pak

    2011-01-01

    Chemical absorption of CO2 and H2S from natural gas was studied theoretically and experimentally using a hollow-fiber membrane contactor (HFMC) in this work. A 2D mathematical model was proposed to study simultaneous transport of CO2 and H2S through a HFMC using methyldiethanolamine (MDEA) as chemical absorbent. The model considers axial and radial diffusion in the HFMC. It also considers convection

  4. Electrochemical investigations of the effect of N-substituted aminosulfonic acids with a piperazinic ring pH buffers on heavy metal processes which may have implications on speciation studies

    Microsoft Academic Search

    Helena M. V. M. Soaresa; Paula C. F. L. Conde

    The influence of piperazine- N,N0-bis(2-ethanesulfonic acid) (PIPES), N-2-hydroxyethylpiperazine-N0-2-ethanesulfonic acid (HEPES) and N-hydroxyethylpiperazine-N0-2-hydroxypropanesulfonic acid (HEPPSO) on the redox processes of cad- mium, lead and zinc was investigated by differential pulse anodic stripping voltammetry (DPASV) and differential pulse polarography (DPP) (only for lead). The studies showed that these pH buffers did neither complex cadmium and zinc nor modify to a significant extent

  5. Electrochemical investigations of the effect of N-substituted aminosulfonic acids with a piperazinic ring pH buffers on heavy metal processes which may have implications on speciation studies

    Microsoft Academic Search

    Helena M. V. M. Soares; Paula C. F. L. Conde

    2000-01-01

    The influence of piperazine-N,N?-bis(2-ethanesulfonic acid) (PIPES), N-2-hydroxyethylpiperazine-N?-2-ethanesulfonic acid (HEPES) and N-hydroxyethylpiperazine-N?-2-hydroxypropanesulfonic acid (HEPPSO) on the redox processes of cadmium, lead and zinc was investigated by differential pulse anodic stripping voltammetry (DPASV) and differential pulse polarography (DPP) (only for lead). The studies showed that these pH buffers did neither complex cadmium and zinc nor modify to a significant extent the reversibility

  6. Density and viscosity of some partially carbonated aqueous alkanolamine solutions and their blends

    SciTech Connect

    Weiland, R.H.; Dingman, J.C.; Cronin, D.B.; Browning, G.J. [Optimized Gas Treating, Inc., Houston, TX (United States)] [Optimized Gas Treating, Inc., Houston, TX (United States)

    1998-05-01

    Very little information is available concerning the effect of acid gas loading on the physical properties of amine-treating solutions flowing through the absorption and regeneration columns used in gas processing. The densities and viscosities of partially carbonated monoethanolamine (MEA), diethanolamine (DEA), and N-methyldiethanolamine (MDEA) solutions were measured at 298 K. With increasing carbon dioxide loadings, significant increases in both density and viscosity were observed. These results were combined with literature data to produce correlations for alkanolamine solution density and viscosity as a function of amine concentration, carbon dioxide loading, and temperature. The resulting single-amine correlations were used to predict the densities and viscosities of DEA + MDEA and MEA + MDEA blends. Predictions are compared with data measured for these blends.

  7. Study on action mechanism of 1-(4-methoxy-2-methylphenyl)piperazine (MMPP) in acquisition, formation, and consolidation of memory in mice.

    PubMed

    Navarrete, Andrés; Flores-Machorro, Francisco X; Téllez-Ballesteros, Ruth I; Alfaro-Romero, Alejandro; Balderas, José Luis; Reyes, Adelfo

    2014-03-01

    In the present study, the mechanism of action of MMPP (1-(4-methoxy-2-methylphenyl) piperazine) in the acquisition (pretraining administration), formation (posttraining administration), and consolidation (pretest administration) of memory was assessed in the passive avoidance test using a short- and long-term memory protocol in mice. MMPP modified avoidance in the acquisition and formation of memory protocols but not in the consolidation protocol. Scopolamine (0.1?mg/kg i.p.), dizocilpine (0.003?mg/kg i.p.), and buspirone (0.1?mg/kg i.p.) completely inhibited MMPP-induced effects on memory acquisition and partially inhibited memory formation in the short-term but not long-term paradigm. This suggested that cholinergic, N-methyl-D-aspartate (NMDA) and 5-hydroxytryptamine-1A (5-HT1A ) receptors were implicated in the MMPP-induced improvements in memory. The sedative, anxiolytic, motor impairment, myorelaxant, and anticonvulsive (pentylenetetrazole-induced seizures) properties of MMPP were also assessed with the compound only showing a nondose-dependent myorelaxation. These results suggest that MMPP can enhance acquisition and formation, but not consolidation, of memory in short-term and long-term protocol via cholinergic, NMDA-glutamatergic, and 5-HT1A receptors. PMID:24648132

  8. Collection and chemical derivatization of airborne phosgene with 1-(2-pyridyl)-piperazine and determination by high performance liquid chromatography

    SciTech Connect

    Rando, R.J.; Poovey, H.G. (Tulane Univ. Medical Center, New Orleans, LA (United States). Section of Bioenvironmental Research); Chang, Shau-nong (Tulane Univ. Medical Center, New Orleans, LA (United States). Dept. of Environmental Health Sciences)

    1993-01-01

    As an alternative to currently available measurement methods, Chromosorb coated with 1-(2-pyridyl)-piperazine (PYP) was evaluated for collection/derivatization of phosgene gas. Solid sorbent tubes contained 100 mg of 2.5% PYP coated on Chromosorb. Phosgene reacts with two equivalents of PYP to form a substituted urea derivative which is desorbed with acetonitrile and determined by reversed phase high performance liquid chromatography with ultraviolet absorbance detection. In comparison to the 4,4[prime]-nitrobenzyl pyridine in diethylphthalate colorimetric technique, the recovery of phosgene from the sorbent tube was quantitative from 0.02 to 1 ppm phosgene and was unaffected by humidity. The limit of detection for a 20 L air sample was estimated to be 0.005 ppm. The utility of the method was further improved by demonstrating the use of triphosgene (bis-(trichloromethyl)-carbonate) in the synthesis of the urea derivative used for standardization, thus eliminating the need for working with gaseous phosgene in preparing analytical standards.

  9. Optically active antifungal azoles: synthesis and antifungal activity of (2 R,3 S)-2-(2,4-difluorophenyl)-3-(5-{2-[4-aryl-piperazin-1-yl]-ethyl}-tetrazol-2-yl\\/1-yl)-1-[1,2,4]-triazol-1-yl-butan-2-ol

    Microsoft Academic Search

    Ram Shankar Upadhayaya; Neelima Sinha; Sanjay Jain; Nawal Kishore; Ramesh Chandra; Sudershan K. Arora

    2004-01-01

    A series of (2R,3S)-2-(2,4-difluorophenyl)-3-(5-{2-[4-aryl-piperazin-1-yl]-ethyl}-tetrazol-2-yl)-1-[1,2,4]-triazol-1-yl-butan-2-ol (11a–n) and (2R,3S)-2-(2,4-difluorophenyl)-3-(5-{2-[4-aryl-piperazin-1-yl]-ethyl}-tetrazole-1-yl)-1-[1,2,4]-triazol-1-yl-butan-2-ol (12a–n) has been synthesized. The antifungal activity of compounds was evaluated by in vitro agar diffusion and broth dilution assay. Compounds 11d and its positional isomer 12d having 3-trifluoromethyl substitution on the phenyl ring of piperazine demonstrated significant antifungal activity against variety of fungal cultures (Candida spp. C. neoformans and Aspergillus spp.). The

  10. Crystal structure of 3-[(4-benzyl-piperazin-1-yl)meth-yl]-5-(thio-phen-2-yl)-2,3-di-hydro-1,3,4-oxa-diazole-2-thione.

    PubMed

    Al-Omary, Fatmah A M; El-Emam, Ali A; Ghabbour, Hazem A; Chidan Kumar, C S; Quah, Ching Kheng; Fun, Hoong-Kun

    2015-03-01

    The title 1,3,4-oxa-diazole-2-thione derivative, C18H20N4OS2, crystallized with two independent mol-ecules (A and B) in the asymmetric unit. The 2-thienyl rings in both mol-ecules are rotationally disordered over two orientations by approximately 180° about the single C-C bond that connects it to the oxa-diazole thione ring; the ratios of site occupancies for the major and minor components were fixed in the structure refinement at 0.8:0.2 and 0.9:0.1 in mol-ecules A and B, respectively. The 1,3,4-oxa-diazole-2-thione ring forms dihedral angles of 7.71?(16), 10.0?(11) and 77.50?(12)° (mol-ecule A), and 6.5?(3), 6.0?(9) and 55.30?(12)° (mol-ecule B) with the major and minor parts of the disordered thio-phene ring and the mean plane of the adjacent piperazine ring, respectively, resulting in approximately V-shaped conformations for the mol-ecules. The piperazine ring in both mol-ecules adopts a chair conformation. The terminal benzene ring is inclined towards the mean plane of the piperazine ring with N-C-C-C torsion angles of -58.2?(3) and -66.2?(3)° in mol-ecules A and B, respectively. In the crystal, no inter-molecular hydrogen bonds are observed. The crystal packing features short S?S contacts [3.4792?(9)?Å] and ?-? inter-actions [3.661?(3), 3.664?(11) and 3.5727?(10)?Å], producing a three-dimensional network. PMID:25844234

  11. (3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrrolidin-2-yl]-methanone: A potent, selective, orally active dipeptidyl peptidase IV inhibitor

    SciTech Connect

    Ammirati, Mark J.; Andrews, Kim M.; Boyer, David D.; Brodeur, Anne M.; Danley, Dennis E.; Doran, Shawn D.; Hulin, Bernard; Liu, Shenping; McPherson, R. Kirk; Orena, Stephen J.; Parker, Janice C.; Polivkova, Jana; Qiu, Xiayang; Soglia, Carolyn B.; Treadway, Judith L.; VanVolkenburg, Maria A.; Wilder, Donald C.; Piotrowski, David W.; Pfizer

    2010-10-01

    A series of 4-substituted proline amides was synthesized and evaluated as inhibitors of dipeptidyl pepdidase IV for the treatment of type 2 diabetes. (3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrrolidin-2-yl]-methanone (5) emerged as a potent (IC{sub 50} = 13 nM) and selective compound, with high oral bioavailability in preclinical species and low plasma protein binding. Compound 5, PF-00734200, was selected for development as a potential new treatment for type 2 diabetes.

  12. Synthesis, radiolabeling, and preliminary biological evaluation of [3H]-1-[(S)-N,O-bis-(isoquinolinesulfonyl)-N-methyl-tyrosyl]-4-(o-tolyl)-piperazine, a potent antagonist radioligand for the P2X7 receptor.

    PubMed

    Romagnoli, Romeo; Baraldi, Pier Giovanni; Pavani, Maria Giovanna; Tabrizi, Mojgan Aghazadeh; Moorman, Allan R; Di Virgilio, Francesco; Cattabriga, Elena; Pancaldi, Cecilia; Gessi, Stefania; Borea, Pier Andrea

    2004-11-15

    The design, synthesis, and preliminary biological evaluation of the first potent radioligand antagonist for the P2X(7) receptor, named [(3)H]-1-[(S)-N,O-bis-(isoquinolinesulfonyl)-N-methyl-tyrosyl]-4-(o-tolyl)-piperazine (compound 13), are reported. This compound bound to human P2X(7) receptors expressed in HEK transfected cells with K(D) and B(max) value of 3.46+/-0.1 nM and 727+/-73 fmol/mg of protein, respectively. The high affinity and facile labeling makes it a promising radioligand for a further characterization of P2X(7) receptor subtype. PMID:15482953

  13. Synthesis, biological evaluation and molecular docking study of novel piperidine and piperazine derivatives as multi-targeted agents to treat Alzheimer's disease.

    PubMed

    Meena, Poonam; Nemaysh, Vishal; Khatri, Manisha; Manral, Apra; Luthra, Pratibha Mehta; Tiwari, Manisha

    2015-03-01

    Development of Multi-Target Directed Ligands (MTDLs) has emerged as a promising approach for targeting complex etiology of Alzheimer's disease (AD). Following this approach, a new series of N'-(4-benzylpiperidin-/piperazin-/benzhydrylpiperazin-1-yl)alkylamine derivatives were designed, synthesized and biologically evaluated as inhibitors of cholinesterases (ChEs), amyloid-beta (A?) self aggregation and also for their radical scavenging activity. The in vitro studies showed that the majority of synthesized derivatives strongly inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 values in the low-nanomolar range, and were clearly more potent than the reference compound donepezil in this regard. Among them, inhibitors 5h and 5k, strongly inhibited AChE, with IC50 value of 6.83nM and 2.13nM, respectively, and particularly, compound 5k was found to be highly selective for AChE (?38-fold). Moreover, both kinetic analysis of AChE inhibition and the docking study suggested that 5k binds simultaneously to catalytic active site and peripheral anionic site of AChE. Besides, these compounds also exhibited greater ability to inhibit self-induced A?1-42 aggregation at 25?M with percentage inhibition from ?54% to 89% and specially compound 5k provided highest inhibition (88.81%). Also, the derivatives containing methoxy and hydroxy groups showed potent oxygen radical absorbance capacity (ORAC) ranging from 2.2- to 4.4-fold of the Trolox value. Furthermore, results of ADMET studies suggested that all compounds exhibited appropriate drug like properties. Taken together, these results suggest that 5k might be a promising lead compound for further AD drug development. PMID:25624107

  14. Effects of two novel D3-selective compounds, NGB 2904 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-9H-fluorene-2-carboxamide] and CJB 090 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridin-2-yl)benzamide], on the reinforcing and discriminative stimulus effects of cocaine in rhesus monkeys.

    PubMed

    Martelle, Jennifer L; Claytor, Renee; Ross, Jason T; Reboussin, Beth A; Newman, Amy Hauck; Nader, Michael A

    2007-05-01

    The present study examined the effects of two novel dopamine D3 receptor compounds, NGB 2904 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-9H-fluorene-2-carboxamide], an antagonist, and CJB 090 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridin-2-yl)benzamide], a partial agonist, in two models of cocaine abuse in rhesus monkeys. To establish a dose range and time course of effects, both compounds were shown to block quinpirole-induced yawning when administered i.m. 15, 30, or 120 min before quinpirole. Next, rhesus monkeys were trained to discriminate i.m. injections of saline (0.5 ml) and cocaine (0.3 mg/kg). Neither D3 compound (0.03-3.0 mg/kg; n=3) substituted for cocaine in any monkey. When given in combination with cocaine, CJB 090 but not NGB 2904 attenuated the discriminative stimulus effects of cocaine, shifting the cocaine dose-response curve to the right. In a separate group of monkeys, responding was maintained under a second-order schedule of either food (1.0-g pellets; n=3) or cocaine (0.1 mg/kg/injection; n=4) presentation. When responding was stable, a dose of NGB 2904 (1.0-5.6 mg/kg i.v.) or CJB 090 (0.3-3.0 mg/kg i.v.) was administered for 5 consecutive days, immediately before the session. CJB 090, but not NGB 2904, decreased cocaine- and food-maintained responding. These data indicate that compounds with relatively high affinity and selectivity for the D3 receptor can attenuate the discriminative and reinforcing stimulus effects of cocaine while not producing cocaine-like effects. The present findings support the continued examination of D3 compounds as pharmacological tools for better understanding the role of this receptor subtype in cocaine addiction and as potential lead compounds for novel therapeutic agents. PMID:17272677

  15. Design, synthesis, radiolabeling and in vivo evaluation of carbon-11 labeled N-[2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3-methoxybenzamide, a potential Positron Emission Tomography tracer for the dopamine D4 receptors

    PubMed Central

    Lacivita, Enza; De Giorgio, Paola; Lee, Irene T.; Rodeheaver, Sean I.; Weiss, Bryan A.; Fracasso, Claudia; Caccia, Silvio; Berardi, Francesco; Perrone, Roberto; Zhang, Ming-Rong; Maeda, Jun; Higuchi, Makoto; Suhara, Tetsuya; Schetz, John A.; Leopoldo, Marcello

    2010-01-01

    Here we describe the design, synthesis, physicochemical, and pharmacological evaluation of D4 dopamine receptor ligands related to N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (2). Structural features were incorporated to increase affinity for the target receptor, to improve selectivity over D2 and sigma1 receptors, to enable labeling with carbon-11 or fluorine-18, and to adjust lipophilicity within the range considered optimal for brain penetration and low nonspecific binding. Compounds 7 and 13 showed the overall best characteristics: nanomolar affinity for the D4 receptor, > 100-fold selectivity over D2 and D3 dopamine receptor 5-HT1A, 5-HT2A and 5-HT2C serotonin receptors and sigma1 receptors, and logP = 2.37–2.55. Following intraperitoneal administration, both compounds rapidly entered the central nervous system. The methoxy of N-[2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3-methoxybenzamide (7) was radiolabelled with carbon-11 and subjected to PET analysis in non-human primate. [11C]7 time-dependently accumulated to saturation in the posterior eye in the region of the retina, a tissue containing a high density of D4 receptors. PMID:20873719

  16. Design, synthesis, radiolabeling, and in vivo evaluation of carbon-11 labeled N-[2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3-methoxybenzamide, a potential positron emission tomography tracer for the dopamine D(4) receptors.

    PubMed

    Lacivita, Enza; De Giorgio, Paola; Lee, Irene T; Rodeheaver, Sean I; Weiss, Bryan A; Fracasso, Claudia; Caccia, Silvio; Berardi, Francesco; Perrone, Roberto; Zhang, Ming-Rong; Maeda, Jun; Higuchi, Makoto; Suhara, Tetsuya; Schetz, John A; Leopoldo, Marcello

    2010-10-28

    Here we describe the design, synthesis, and evaluation of physicochemical and pharmacological properties of D(4) dopamine receptor ligands related to N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (2). Structural features were incorporated to increase affinity for the target receptor, to improve selectivity over D(2) and ?(1) receptors, to enable labeling with carbon-11 or fluorine-18, and to adjust lipophilicity within the range considered optimal for brain penetration and low nonspecific binding. Compounds 7 and 13 showed the overall best characteristics: nanomolar affinity for the D(4) receptor, >100-fold selectivity over D(2) and D(3) dopamine receptors, 5-HT(1A), 5-HT(2A), and 5-HT(2C) serotonin receptors and ?(1) receptors, and log?P = 2.37-2.55. Following intraperitoneal administration in mice, both compounds rapidly entered the central nervous system. The methoxy of N-[2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3-methoxybenzamide (7) was radiolabeled with carbon-11 and subjected to PET analysis in non-human primate. [(11)C]7 time-dependently accumulated to saturation in the posterior eye in the region of the retina, a tissue containing a high density of D(4) receptors. PMID:20873719

  17. 9?-Hy­droxy-12-{[4-(4-meth­oxy­phen­yl)piperazin-1-yl]meth­yl}-4,8-dimethyl-3,14-dioxatricyclo­[9.3.0.02,4]tetra­dec-7-en-13-one

    PubMed Central

    Moumou, Mohamed; Benharref, Ahmed; Daran, Jean-Claude; Mellouki, Fouad; Berraho, Moha

    2012-01-01

    The title compound, C26H36N2O5, was synthesized from 9?-hy­droxy­parthenolide (9?-hy­droxy-4,8-dimethyl-12-methyl­ene-3,14-dioxatricyclo­[9.3.0.02,4]tetra­dec-7-en-13-one), wich was isolated from the chloro­form extract of the aerial parts of Anvillea radiata. The mol­ecule is built up from fused five- and ten-membered rings with the meth­oxy­phenyl­piperazine group as a substituent. The ten-membered ring adopts an approximate chair–chair conformation, while the piperazine ring displays a chair conformation and the five-membered ring a flattened envelope conformation; the C(H)—C—C(H) atoms representing the flap lie out of the mean plane through the remaining four atoms by 0.343?(3)?Å. The dihedral angle between the mean planes of the ten-membered ring and the lactone ring is 18.12?(14)°. An intra­molecular O—H?N hydrogen bond occurs. The crystal structure features weak C—H?O inter­actions. PMID:22412505

  18. 12-{[4-(2-Fluoro­phen­yl)piperazin-1-yl]­meth­yl}-9?-hy­droxy-4,8-dimethyl-3,14-dioxatricyclo­[9.3.0.02,4]tetra­dec-7-en-13-one

    PubMed Central

    Moumou, Mohamed; Benharref, Ahmed; Daran, Jean Claude; Outouch, Rachid; Berraho, Moha

    2012-01-01

    The title compound, C25H33FN2O4, was synthesized from 9?-hy­droxy­parthenolide (9?-hy­droxy-4,8-dimethyl-12-methyl­ene-3,14-dioxatricyclo­[9.3.0.02,4]tetra­dec-7-en-13-one), which was isolated from the chloro­form extract of the aerial parts of Anvillea radiata. The asymmetric unit contains two independent mol­ecules. In each mol­ecule, the ten-membered ring displays an approximative chair–chair conformation. Each of the piperazine rings adopts a perfect chair conformation, while both lactone rings show an envelope conformation, one with the C atom bearing the piperazin-1-ylmethyl group as the flap, the other with the junction C atom not attached to the ring O atom as the flap. The dihedral angles between the least-squares planes through the ten- and five-membered rings in the two mol­ecules are similar [19.1?(3) and 16.2?(3)°]. An intra­molecular O—H?N hydrogen bond stabilizes the mol­ecular conformation. The crystal packing is stabilized by C—H?O hydrogen bonds. PMID:22412621

  19. Solubility of nitrous oxide in amine solutions

    SciTech Connect

    Bensetiti, Z.; Iliuta, I.; Larachi, F.; Grandjean, B.P.A. [Laval Univ., Quebec (Canada)] [Laval Univ., Quebec (Canada)

    1999-01-01

    The solubility of nitrous oxide (N{sub 2}O) in 13 amine solvents and solutions was correlated to amine mole fractions and temperature using feedforward neural networks. This general correlation, using a massive database, predicted N{sub 2}O solubility at temperatures between 283 and 398 K in pure solvents [H{sub 2}O, monoethanolamine (MEA), diethanolamine (DEA), methyldiethanolamine (MDEA), and 2-amino-2-methyl-1-propanolamine (AMP)], in binary aqueous amine solutions [H{sub 2}O/MEA, H{sub 2}O/DEA, H{sub 2}O/MDEA, and H{sub 2}O/AMP], and in ternary aqueous amine blends [AMP/MDEA/H{sub 2}O, AMP/DEA/H{sub 2}O, DEA/MDEA/H{sub 2}O, MDEA/MEA/H{sub 2}O, and AMP/MEA/H{sub 2}O]. Combined with the N{sub 2}O analogy, this present improved correlation can be advantageously implemented in amine plant design software and procedures for the prediction of CO{sub 2} solubility in amine blend solutions over wide temperature and concentration ranges.

  20. Collection of VLE data for acid gas - alkanolamine systems using Fourier transform infrared spectroscopy. Final report, September 29, 1990--September 30, 1996

    SciTech Connect

    Bullin, J.A.; Rogers, W.J.

    1996-11-01

    This report describes research from September 29, 1990 through September 30, 1996, involving the development a novel Fourier transform infrared (FTIR) spectroscopic apparatus and method for measuring vapor - liquid equilibrium (VLE) systems of carbon dioxide and hydrogen sulfide with aqueous alkanolamine solutions. The original apparatus was developed and modified as it was used to collect VLE data on acid gas systems. Vapor and liquid calibrations were performed for spectral measurements of hydrogen sulfide and carbon dioxide in the vapor and in solution with aqueous diethanolamine (DEA) and methyldiethanolamine (MDEA). VLE measurements were made of systems of hydrogen sulfide and carbon dioxide in 20 wt % DEA at 50{degrees}C and 40{degrees}C. VLE measurements were made of systems of hydrogen sulfide and carbon dioxide in 50 wt% and 23 wt% MDEA at 40{degrees}C and in 23 wt% MDEA at 50{degrees}C. VLE measurements were made of systems of hydrogen sulfide and carbon dioxide in 35 wt% MDEA + 5 wt% DEA and in 35 wt% MDEA + 10 wt% DEA at 40{degrees}C and 50{degrees}C. Measurements were made of residual amounts of carbon dioxide in each VLE system. The new FTIR spectrometer is now a consistently working and performing apparatus.

  1. 10?-Hy­droxy-4,9-dimethyl-13-[(4-phenyl­piperazin-1-yl)meth­yl]-3,8,15-trioxatetra­cyclo­[10.3.0.02,4.07,9]tetra­decan-14-one

    PubMed Central

    Moumou, Mohamed; Benharref, Ahmed; Oudahmane, Abdelghani; Elhakmaoui, Ahmed; Berraho, Moha

    2011-01-01

    The title compound, C25H34N2O5, was synthesized from 9?-hy­droxy­parthenolide (9?-hy­droxy-4,8-dimethyl-12-methyl­ene-3,14-dioxatricyclo­[9.3.0.02,4]tetra­dec-7-en-13-one), which was isolated from the chloro­form extract of the aerial parts of Anvillea radiata. The mol­ecule contains a fused five- and ten-membered ring system. The ten-membered ring adopts an approximate chair–chair conformation, while the five-membered ring is in an envelope conformation, with the C atom closest to the hy­droxy group forming the flap. The piperazine ring is in a chair conformation. In the crystal, O—H?O hydrogen bonds connect mol­ecules into chains along [100]. Weak inter­molecular C—H?O hydrogen bonds are also present. PMID:22220002

  2. 4-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide (ML267), a Potent Inhibitor of Bacterial Phosphopantetheinyl Transferase That Attenuates Secondary Metabolism and Thwarts Bacterial Growth

    PubMed Central

    2015-01-01

    4?-Phosphopantetheinyl transferases (PPTases) catalyze a post-translational modification essential to bacterial cell viability and virulence. We present the discovery and medicinal chemistry optimization of 2-pyridinyl-N-(4-aryl)piperazine-1-carbothioamides, which exhibit submicromolar inhibition of bacterial Sfp-PPTase with no activity toward the human orthologue. Moreover, compounds within this class possess antibacterial activity in the absence of a rapid cytotoxic response in human cells. An advanced analogue of this series, ML267 (55), was found to attenuate production of an Sfp-PPTase-dependent metabolite when applied to Bacillus subtilis at sublethal doses. Additional testing revealed antibacterial activity against methicillin-resistant Staphylococcus aureus, and chemical genetic studies implicated efflux as a mechanism for resistance in Escherichia coli. Additionally, we highlight the in vitro absorption, distribution, metabolism, and excretion and in vivo pharmacokinetic profiles of compound 55 to further demonstrate the potential utility of this small-molecule inhibitor. PMID:24450337

  3. 1-[Bis(4-fluoro­phen­yl)meth­yl]-4-[(2Z)-3-phenyl­prop-2-en-1-yl]piperazine-1,4-diium dichloride hemihydrate

    PubMed Central

    Shivaprakash, S.; Chandrasekara Reddy, G.; Jasinski, Jerry P.

    2014-01-01

    The asymmetric unit of the title monohydrated salt, 2C26H28F2N2 2+·4Cl?.H2O, consists of a 1-[bis­(4-fluoro­phen­yl)meth­yl]-4-[(2Z)-3-phenyl­prop-2-en-1-yl]piperazine-1,4-diium cation with a diprotonated piperizine ring in close proximity to two chloride anions and a single water mol­ecule that lies on a twofold rotation axis. In the cation, the piperazine ring adopts a slightly distorted chair conformation. The dihedral angles between the phenyl ring and the 4-fluoro­phenyl rings are 89.3?(9) and 35.0?(5)°. The two fluoro­phenyl rings are inclined at 65.0?(5)° to one another. In the crystal, N—H?Cl hydrogen bonds and weak C—H?Cl inter­molecular inter­actions link the mol­ecules into chains along [010]. In addition, weak C—H?O inter­actions between the piperizine and prop-2-en-1-yl groups with the water mol­ecule, along with weak C—H?Cl inter­actions between the prop-2en-1-yl and methyl groups with the chloride ions, weak C—H?F inter­actions between the two fluoro­phenyl groups and weak O—H?Cl inter­actions between the water mol­ecule and chloride ions form a three-dimensional supra­molecular network. PMID:24940270

  4. Physical solubility of carbon dioxide in aqueous alkanolamines via nitrous oxide analogy

    SciTech Connect

    Browning, G.J.; Weiland, R.H. (Univ. of Newcastle, Callaghan, New South Wales (Australia). Dept. of Chemical Engineering)

    1994-10-01

    In the petrochemical and natural gas industry, the removal of carbon dioxide and hydrogen sulfide from process gas streams is commonly achieved by reacting these impurities with aqueous alkanolamines. Van Krevelen coefficients for protonated monoethanolamine (MEA), diethanolamine (DEA), and methyldiethanolamine (MDEA), the carbamates of MEA and DEA, and the bicarbonate ion have been determined experimentally from measurements of the solubility of N[sub 2]O at 25 C and atmospheric pressure in aqueous solutions of these ions. Measured values different significantly from values recommended by others in the absence of experimental data. By analogy with N[sub 2]O, the solubility of carbon dioxide in the same solutions can be estimated.

  5. Surface tension of aqueous solutions of diethanolamine and triethanolamine from 25 C to 50 C

    SciTech Connect

    Vazquez, G.; Alvarez, E.; Rendo, R.; Romero, E.; Navaza, J.M. [Univ. of Santiago de Compostela (Spain). Dept. of Chemical Engineering] [Univ. of Santiago de Compostela (Spain). Dept. of Chemical Engineering

    1996-07-01

    Aqueous solutions of alkanolamines such as monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA), N-methyldiethanolamine (MDEA), and 2-amino-2-methyl-1-propanol (AMP) are good solvents for the removal of acid gases such CO{sub 2} and H{sub 2}S from the gas streams of many processes in the natural gas, ammonia synthesis, and some chemical industries. The surface tension of aqueous solutions of diethanolamine and triethanolamine was measured over the entire concentration range at temperatures of 25 C to 50 C. The experimental values were correlated with temperature and with mole fraction. The maximum deviation was in both cases always less than 0.5%.

  6. (1S,2R,3R,6R,7S,8R,10S,11S)-13-{[4-(4-Chloro­phen­yl)piperazin-1-yl]meth­yl}-10-hy­droxy-4,9-dimethyl-3,8,15-trioxatetra­cyclo­[10.3.0.02,4.07,9]penta­decan-14-one

    PubMed Central

    Moumou, Mohamed; Benharref, Ahmed; El Ammari, Lahcen; Adil, Mina; Berraho, Moha

    2012-01-01

    The title compound, C25H33ClN2O5, was synthesized from 9?-hy­droxy­parthenolide (9?-hy­droxy-4,8-dimethyl-12-methyl­ene-3,14-dioxatricyclo­[9.3.0.02,4]tetra­dec-7-en-13-one), which was isolated from the chloro­form extract of the aerial parts of Anvillea radiata. The mol­ecule is built up from fused five- and ten-membered rings with two additional ep­oxy ring systems and a chloro­phenyl­piperazine group as a substituent. The ten-membered ring adopts an approximate chair–chair conformation, while the piperazine ring displays a chair conformation and the five-membered ring shows an envelope conformation with the C atom closest to the hy­droxy group forming the flap. The mol­ecular conformation is stabilized by an intra­molecular O—H?N hydrogen bond between the hy­droxy group and a piperazine N atom. The crystal structure is stabilized by weak C—H?O inter­actions. PMID:22606094

  7. 10?-Hy­droxy-13-{[4-(4-meth­oxy­phen­yl)piperazin-1-yl]meth­yl}-4,9-dimethyl-3,8,15-trioxatetra­cyclo­[10.3.0.02,4.07,9]penta­decan-14-one

    PubMed Central

    Moumou, Mohamed; Benharref, Ahmed; Daran, Jean Claude; Outouch, Rachid; Berraho, Moha

    2012-01-01

    The title compound, C26H36N2O6, was synthesized from 9?-hy­droxy­parthenolide (9?-hy­droxy-4,8-dimethyl-12-methylen-3,14-dioxa-tricyclo­[9.3.0.02,4]tetra­dec-7-en-13-one), which was isolated from the chloro­form extract of the aerial parts of Anvillea radiata. The mol­ecule is built up from fused five- and ten-membered rings with two additional ep­oxy ring systems and a meth­oxy­phenyl­piperazine group as a substituent. The ten-membered ring adopts an approximate chair–chair conformation, while the piperazine ring displays a chair conformation and the five-membered ring shows an envelope conformation with the C atom closest to the hy­droxy group forming the flap. The mol­ecular conformation is determined by an O—H?N hydrogen bond between the hy­droxy group and a piperazine N atom. The crystal structure is built up by weak C—H?O inter­actions. PMID:22412599

  8. Amine plant troubleshooting and optimization

    SciTech Connect

    Abry, R.G.F. [Dow Chemical Co., Ft. Saskatchewan, Alberta (Canada); DuPart, M.S. [Dow Chemical Co., Freeport, TX (United States)

    1995-04-01

    A systematic method for troubleshooting and optimization of amine plants, if properly used, will result in fewer plant upsets, quick and correct responses to changing conditions and long-term profitable operations of any amine unit. It is important for amine plants to maintain safe, continuous and optimized operations for short- and long-term success. Effective and fast resolution of maine unit upsets plays a large part in this success. These considerations are as important in plants using generic amines such as monoethanolamine (MEA), diethanolamine (DEA), methyldiethanolamine (MDEA) and specialty amines based on MDEA. The key to troubleshooting and optimization is a systematic approach. Developing and using control charts can also be used to monitor amine plant operations. By using these techniques collectively, a formal method for troubleshooting and optimization can be established. This will ultimately result in a more trouble-free, continuous operation.

  9. Acid gas absorption in aqueous solutions of mixed amines

    SciTech Connect

    Rinker, E.B.; Ashour, S.S.; Sandall, O.C. [Univ. of California, Santa Barbara, CA (United States)

    1996-12-31

    A mass transfer model has been developed to describe the rate of absorption (or desorption) of H{sub 2}S and CO{sub 2} in aqueous blends of a tertiary and a secondary or a primary amine. The model is based on penetration theory, and all significant chemical reactions are incorporated in the model. The reactions are taken to be reversible, with reactions involving only a proton transfer considered to be at equilibrium. The particular amines studied in this research were methyldiethanolamine (MDEA), a tertiary amine, and diethanolamine (DEA), a secondary amine. Key physicochemical data needed in the model, such as diffusion coefficients, kinetic rate constants, and gas solubilities, were measured. Experimental absorption rates of CO{sub 2} and H{sub 2}S were measured in a model gas-liquid contacting device and were compared with model predictions. Experiments were carried out for single amine solutions (both MDEA and DEA) and for amine blends.

  10. Exploring the Solid State Properties of Enzymatic Poly(amine-co-ester) Terpolymers to Expand their Applications in Gene Transfection

    PubMed Central

    Voevodina, Irina; Scandola, Mariastella; Zhang, Junwei; Jiang, Zhaozhong

    2014-01-01

    Polymers bearing amino functional groups are an important class of materials capable of serving as non-viral carriers for DNA delivery to living cells. In this work biodegradable poly(amine-co-ester) terpolymers were synthesized via ring-opening and polycondensation copolymerization of lactone (?-caprolactone (CL), ?-dodecalactone, ?-pentadecalactone (PDL), and ?-hexadecalactone) with diethyl sebacate (DES) and N-methyldiethanolamine (MDEA) in diphenyl ether, catalyzed by Candida antarctica lipase B (CALB). All lactone-DES-MDEA terpolymers had random distributions of lactone, sebacate, MDEA repeat units in the polymer chains. PDL-DES-MDEA terpolymers were studied in the composition range from 21 mol% to 90 mol% PDL whereas the terpolymers with other lactones were investigated at a single composition (80 mol% lactone). DSC and WAXS analyses showed that all investigated terpolymers crystallize in their respective homopolylactone crystal lattice. Terpolymers with large lactones and a high lactone content melt well above room temperature and are hard solids, whereas terpolymers with small lactones (e.g. CL) or with a low lactone content melt below/around ambient temperature and are waxy/gluey materials. Given the importance of hydrophobicity in influencing gene delivery, water contact angle measurements were carried out on lactone-DES-MDEA terpolymers showing that it is possible to tune the hydrophilic-to-hydrophobic balance by varying polymer composition and size of lactone units. To demonstrate the feasibility of using solid terpolymers as nanocarriers for DNA delivery, PDL-DES-MDEA copolymers with 65–90% PDL were successfully transformed into free-standing nanoparticles with average particle size ranging from 163 to 175 nm. Our preliminary results showed that LucDNA-loaded nanoparticles of the terpolymer with 65% PDL were effective for luciferase gene transfection of HEK293 cells. PMID:24683469

  11. Poly[[di-aqua-[?-1,4-bis(pyridin-4-ylmeth-yl)piperazine-?(2) N:N']{?-2,2'-[(1,4-phenyl-ene)bis(-oxy)]di-acetato-?(2) O:O'}cobalt(II)] penta-hydrate].

    PubMed

    Sample, Alexander D; LaDuca, Robert L

    2014-06-01

    In the title compound, {[Co(C10H8O6)(C16H20N4)(H2O)2]·5H2O} n , octa-hedrally coordinated Co(II) ions on crystallographic inversion centres are bound by trans O atoms belonging to two hydro-quinone-O,O'-di-acetate (hqda) anions {systematic name: 2,2'-[(1,4-phenyl-ene)bis-(-oxy)]di-acetate}, two trans-pyridine N-donor atoms from two bis-(pyridin-4-ylmeth-yl)piperazine (4-bpmp) ligands, and two trans aqua ligands. The exobidentate hqda and 4-bpmp ligands form [Co(hqda)(4-bpmp)(H2O)2] n coordination polymer layers parallel to (110) that are anchored into the full crystal structure by O-H?O hydrogen bonding between aqua ligands and ligated hqda O atoms. Disordered water mol-ecules of crystallization occupy incipient channels along [100]. However, these could not modeled reliably and so they were treated with SQUEEZE in PLATON [Spek (2009 ?). Acta Cryst. D65, 148-155]; the crystal data take the presence of these mol-ecules into account. The crystal under investigation was twinned by non-merohedry, the twin fraction of the components being 53.3% and 46.7%. Only data from the major twin component were used in the refinement. PMID:24940193

  12. N-(3-Fluoro-4-(4-(2-methoxy or 2,3-dichlorophenyl) piperazine-1-yl)-butyl)-aryl carboxamides as Selective Dopamine D3 Receptor Ligands: Critical Role of the Carboxamide Linker for D3 Receptor Selectivity

    PubMed Central

    Banala, Ashwini K.; Levy, Benjamin A.; Khatri, Sameer S.; Furman, Cheryse A.; Roof, Rebecca A.; Mishra, Yogesh; Griffin, Suzy A.; Sibley, David R.; Luedtke, Robert R.; Newman, Amy Hauck

    2011-01-01

    N-(3-fluoro-4-(4-(2,3-dichloro- or 2-methoxyphenyl)piperazine-1-yl)-butyl)-aryl carboxamides were prepared and evaluated for binding and function at dopamine D3 (D3R) and D2 receptors (D2R). In this series, we discovered some of the most D3R selective compounds reported to date, (e.g. 8d and 8j >1000-fold D3R-selective over D2R.) In addition, chimeric receptor studies further identified the second extracellular (E2) loop as an important contributor to D3R binding selectivity. Further, compounds lacking the carbonyl group in the amide linker were synthesized and while these amine-linked analogues bound with similar affinities to the amides at D2R, this modification dramatically reduced binding affinities at D3R by >100-fold (e.g. D3RKi for 15b = 393 v. for 8j = 2.6 nM) resulting in compounds with significantly reduced D3R selectivity. This study supports a pivotal role for the D3R E2 loop and the carbonyl group in the 4-phenylpiperazine class of compounds and further reveals a point of separation between structure-activity relationships at D3R and D2R. PMID:21495689

  13. A Novel Anti-Cancer Agent, 1-(3,5-Dimethoxyphenyl)-4-[(6-Fluoro-2-Methoxyquinoxalin-3-yl)Aminocarbonyl] Piperazine (RX-5902), Interferes With ?-Catenin Function Through Y593 Phospho-p68 RNA Helicase.

    PubMed

    Kost, Gina Chun; Yang, Mi Young; Li, Liangwei; Zhang, Yinwei; Liu, Chia-Yi; Kim, Deog Joong; Ahn, Chang-Ho; Lee, Young Bok; Liu, Zhi-Ren

    2015-08-01

    1-(3,5-Dimethoxyphenyl)-4-[(6-fluoro-2-methoxyquinoxalin-3-yl)aminocarbonyl] piperazine (RX-5902) exhibits strong growth inhibition in various human cancer cell lines with IC50 values ranging between 10 and 20?nM. In this study, we demonstrate that p68 RNA helicase is a cellular target of RX-5902 by the drug affinity responsive target stability (DARTS) method, and confirmed the direct binding of (3) H-labeled RX-5902 to Y593 phospho-p68 RNA helicase. We further demonstrated RX-5902 inhibited the ?-catenin dependent ATPase activity of p68 RNA helicase in an in vitro system. Furthermore, we showed that treatment of cancer cells with RX-5902 resulted in the downregulation of the expression of certain genes, which are known to be regulated by the ?-catenin pathway, such as c-Myc, cyclin D1 and p-c-Jun. Therefore, our study indicates that the inhibition of Y593 phospho-p68 helicase - ?-catenin interaction by direct binding of RX-5902 to Y593 phospho-p68 RNA helicase may contribute to the anti-cancer activity of this compound. J. Cell. Biochem. 116: 1595-1601, 2015. © 2015 Wiley Periodicals, Inc. PMID:25649741

  14. Neuroprotective targets through which 6-acetyl-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one (SN79), a sigma receptor ligand, mitigates the effects of methamphetamine in vitro

    PubMed Central

    Kaushal, Nidhi; Robson, Matthew J.; Rosen, Abagail; McCurdy, Christopher R.; Matsumoto, Rae R.

    2014-01-01

    Exposure to high or repeated doses of methamphetamine can cause hyperthermia and neurotoxicity, which are thought to increase the risk of developing a variety of neurological conditions. Sigma receptor antagonism can prevent methamphetamine-induced hyperthermia and neurotoxicity, but the underlying cellular targets through which the neuroprotection is conveyed remain unknown. Differentiated NG108-15 cells were thus used as a model system to begin elucidating the neuroprotective mechanisms targeted by sigma receptor antagonists to mitigate the effects of methamphetamine. In differentiated NG108-15 cells, methamphetamine caused the generation of reactive oxygen/nitrogen species, an increase in PERK-mediated endoplasmic reticulum stress and the activation of caspase-3, -8 and -9, ultimately resulting in apoptosis at micromolar concentrations, and necrotic cell death at higher concentrations. The sigma receptor antagonist, 6-acetyl-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one (SN79), attenuated methamphetamine-induced increases in reactive oxygen/nitrogen species, activation of caspase-3,-8 and-9 and accompanying cellular toxicity. In contrast, 1,3-di(2-tolyl)-guanidine (DTG), a sigma receptor agonist, shifted the dose response curve of methamphetamine-induced cell death towards the left. To probe the effect of temperature on neurotoxicity, NG108-15 cells maintained at an elevated temperature (40 °C) exhibited a significant and synergistic increase in cell death in response to methamphetamine, compared to cells maintained at a normal cell culture temperature (37 °C). SN79 attenuated the enhanced cell death observed in the methamphetamine-treated cells at 40 °C. Together, the data demonstrate that SN79 reduces methamphetamine-induced reactive oxygen/nitrogen species generation and caspase activation, thereby conveying neuroprotective effects against methamphetamine under regular and elevated temperature conditions. PMID:24380829

  15. Neuroprotective targets through which 6-acetyl-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one (SN79), a sigma receptor ligand, mitigates the effects of methamphetamine in vitro.

    PubMed

    Kaushal, Nidhi; Robson, Matthew J; Rosen, Abagail; McCurdy, Christopher R; Matsumoto, Rae R

    2014-02-01

    Exposure to high or repeated doses of methamphetamine can cause hyperthermia and neurotoxicity, which are thought to increase the risk of developing a variety of neurological conditions. Sigma receptor antagonism can prevent methamphetamine-induced hyperthermia and neurotoxicity, but the underlying cellular targets through which the neuroprotection is conveyed remain unknown. Differentiated NG108-15 cells were thus used as a model system to begin elucidating the neuroprotective mechanisms targeted by sigma receptor antagonists to mitigate the effects of methamphetamine. In differentiated NG108-15 cells, methamphetamine caused the generation of reactive oxygen/nitrogen species, an increase in PERK-mediated endoplasmic reticulum stress and the activation of caspase-3, -8 and -9, ultimately resulting in apoptosis at micromolar concentrations, and necrotic cell death at higher concentrations. The sigma receptor antagonist, 6-acetyl-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one (SN79), attenuated methamphetamine-induced increases in reactive oxygen/nitrogen species, activation of caspase-3, -8 and -9 and accompanying cellular toxicity. In contrast, 1,3-di(2-tolyl)-guanidine (DTG), a sigma receptor agonist, shifted the dose response curve of methamphetamine-induced cell death towards the left. To probe the effect of temperature on neurotoxicity, NG108-15 cells maintained at an elevated temperature (40 °C) exhibited a significant and synergistic increase in cell death in response to methamphetamine, compared to cells maintained at a normal cell culture temperature (37 °C). SN79 attenuated the enhanced cell death observed in the methamphetamine-treated cells at 40 °C. Together, the data demonstrate that SN79 reduces methamphetamine-induced reactive oxygen/nitrogen species generation and caspase activation, thereby conveying neuroprotective effects against methamphetamine under regular and elevated temperature conditions. PMID:24380829

  16. Determination of nitrogen mustard hydrolysis products, ethanolamines by gas chromatography-mass spectrometry after tert-butyldimethylsilyl derivatization.

    PubMed

    Ohsawa, Isaac; Seto, Yasuo

    2006-07-28

    A method for determining N-ethyldiethanolamine (EDEA), N-methyldiethanolamine (MDEA) and triethanolamine (TEA), hydrolysis products of nitrogen mustards, in water, urine and blood samples using gas chromatography-mass spectrometry (GC-MS) after derivatization by tert-butyldimethylsilylation (TBDMS) is described. The sample solution was evaporated to dryness, and reacted with N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) at 60 degrees C for 1h. The TBDMS derivatives were separated on a DB-5 column and detected by electron-ionization MS. The quantitation of EDEA, MDEA and TEA was performed by measuring the respective peak areas on the extracted ion chromatograms of m/z 216, m/z 202 and m/z 346, respectively, using nonadecane (C19), the peak area of which was measured at m/z 268, as an internal standard. When the water sample was initially analyzed, considerable loss of EDEA, MDEA and TEA occurred by evaporation. The addition of hydrochloric acid (HCl) to the water sample (final 1 mM), however, permitted quantitative recoveries to be achieved (88%, 88% and 79% for EDEA-(TBDMS)2, MDEA-(TBDMS)2 and TEA-(TBDMS)3, respectively). The limits of detections (LODs, scan mode, S/N = 3) were 2.5, 2.5 and 10 ng/ml for EDEA, MDEA and TEA, respectively. Ethanolamines could be also determined in urine samples (volume 0.1 ml), with reasonable recoveries of 72-100% by the addition of HCl (final 1 mM). For the analysis of serum samples, the sample was precipitated by the addition of perchloric acid (final 3.2%), and the resulting supernatant was neutralized with potassium carbonate, and then acidified by the addition of HCl. The recovery of TBDMS derivatives of ethanolamines was found to rather low (7-31%). PMID:16707130

  17. Ether modifications to 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine (SA4503): effects on binding affinity and selectivity for sigma receptors and monoamine transporters.

    PubMed

    Xu, Rong; Lord, Sarah A; Peterson, Ryan M; Fergason-Cantrell, Emily A; Lever, John R; Lever, Susan Z

    2015-01-01

    Two series of novel ether analogs of the sigma (?) receptor ligand 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine (SA4503) have been prepared. In one series, the alkyl portion of the 4-methoxy group was replaced with allyl, propyl, bromoethyl, benzyl, phenethyl, and phenylpropyl moieties. In the second series, the 3,4-dimethoxy was replaced with cyclic methylenedioxy, ethylenedioxy and propylenedioxy groups. These ligands, along with 4-O-des-methyl SA4503, were evaluated for ?1 and ?2 receptor affinity, and compared to SA4503 and several known ether analogs. SA4503 and a subset of ether analogs were also evaluated for dopamine transporter (DAT) and serotonin transporter (SERT) affinity. The highest ?1 receptor affinities, Ki values of 1.75-4.63 nM, were observed for 4-O-des-methyl SA4503, SA4503 and the methylenedioxy analog. As steric bulk increased, ?1 receptor affinity decreased, but only to a point. Allyl, propyl and bromoethyl substitutions gave ?1 receptor Ki values in the 20-30 nM range, while bulkier analogs having phenylalkyl, and Z- and E-iodoallyl, ether substitutions showed higher ?1 affinities, with Ki values in the 13-21 nM range. Most ligands studied exhibited comparable ?1 and ?2 affinities, resulting in little to no subtype selectivity. SA4503, the fluoroethyl analog and the methylenedioxy congener showed modest six- to fourteen-fold selectivity for ?1 sites. DAT and SERT interactions proved much more sensitive than ? receptor interactions to these structural modifications. For example, the benzyl congener (?1Ki=20.8 nM; ?2Ki=16.4 nM) showed over 100-fold higher DAT affinity (Ki=121 nM) and 6-fold higher SERT affinity (Ki=128nM) than the parent SA4503 (DAT Ki=12650 nM; SERT Ki=760 nM). Thus, ether modifications to the SA4503 scaffold can provide polyfunctional ligands having a broader spectrum of possible pharmacological actions. PMID:25468036

  18. Viscosities of aqueous blended amines

    SciTech Connect

    Hsu, C.H.; Li, M.H. [Chung Yuan Christian Univ., Chung Li (Taiwan, Province of China). Dept. of Chemical Engineering] [Chung Yuan Christian Univ., Chung Li (Taiwan, Province of China). Dept. of Chemical Engineering

    1997-07-01

    Solutions of alkanolamines are an industrially important class of compounds used in the natural gas, oil refineries, petroleum chemical plants, and synthetic ammonia industries for the removal of acidic components like CO{sub 2} and H{sub 2}S from gas streams. The viscosities of aqueous mixtures of diethanolamine (DEA) + N-methyldiethanolamine (MDEA), DEA + 2-amino-2-methyl-1-propanol (AMP), and monoethanolamine (MEA) + 2-piperidineethanol (2-PE) were measured from 30 C to 80 C. A Redlich-Kister equation for the viscosity deviation was applied to represent the viscosity. On the basis of the available viscosity data for five ternary systems, MEA + MDEA + H{sub 2}O, MEA + AMP + H{sub 2}O, DEA + MDEA + H{sub 2}O, DEA + AMP + H{sub 2}O, and MEA + 2-PE + H{sub 2}O, a generalized set of binary parameters were determined. For the viscosity calculation of the systems tested, the overall average absolute percent deviation is about 1.0% for a total of 499 data points.

  19. Densities of aqueous blended amines

    SciTech Connect

    Hsu, C.H.; Li, M.H. [Chung Yuan Christian Univ., Chung Li (Taiwan, Province of China). Dept. of Chemical Engineering] [Chung Yuan Christian Univ., Chung Li (Taiwan, Province of China). Dept. of Chemical Engineering

    1997-05-01

    Solutions of alkanolamines are an industrially important class of compounds used in the natural gas and synthetic ammonia industries and petroleum chemical plants for the removal of CO{sub 2} and H{sub 2}S from gas streams. The densities of aqueous mixtures of diethanolamine (DEA) + N-methyldiethanolamine (MDEA) + water, DEA + 2-amino-2-methyl-1-propanol (AMP) + water, and monoethanolamine (MEA) + 2-piperidineethanol (2-PE) + water were measured from 30 C to 80 C. A Redlich-Kister equation of the excess volume was applied to represent the density. Based on the available density data for five ternary systems: MEA + MDEA + H{sub 2}O, MEA + AMP + H{sub 2}O, DEA + MDEA + H{sub 2}O, DEA + AMP + H{sub 2}O, and MEA + 2-PE + H{sub 2}O, a generalized set of binary parameters were determined. The density calculations show quite satisfactory results. The overall average absolute percent deviation is about 0.04% for a total of 686 data points.

  20. 10?-Hy­droxy-13-{[4-(2-hy­droxy­phen­yl)piperazin-1-yl]meth­yl}-4,9-dimethyl-3,8,15-trioxatetra­cyclo­[10.3.0.02,4.07,9]penta­decan-14-one

    PubMed Central

    Moumou, Mohamed; Benharref, Ahmed; El Ammari, Lahcen; Adil, Mina; Berraho, Moha

    2012-01-01

    The title compound, C25H34N2O6, was synthesized from 9?-hy­droxy­parthenolide (9?-hy­droxy-4,8-dimethyl-12-methyl­ene-3,14-dioxatricyclo­[9.3.0.02,4]tetra­dec-7-en-13-one), which was isolated from the chloro­form extract of the aerial parts of Anvillea radiata. The ten-membered ring adopts an approximate chair–chair conformation, while the piperazine ring displays a near regular chair conformation and the five-membered ring an envelope conformation with the C atom closest to the hy­droxy group forming the flap. The mol­ecular conformation is stabilized by an O—H?N hydrogen bond, which generates an S(7) loop, and the crystal structure features weak C—H?O inter­actions. PMID:22590215

  1. Discovery of 1-{4-[3-Fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperazin-1-yl}-ethanone (GNE-3500): a Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C (RORc or ROR?) Inverse Agonist.

    PubMed

    Fauber, Benjamin P; René, Olivier; Deng, Yuzhong; DeVoss, Jason; Eidenschenk, Céline; Everett, Christine; Ganguli, Arunima; Gobbi, Alberto; Hawkins, Julie; Johnson, Adam R; La, Hank; Lesch, Justin; Lockey, Peter; Norman, Maxine; Ouyang, Wenjun; Summerhill, Susan; Wong, Harvey

    2015-07-01

    Retinoic acid receptor-related orphan receptor C (RORc, ROR?, or NR1F3) is a nuclear receptor that plays a major role in the production of interleukin (IL)-17. Considerable efforts have been directed toward the discovery of selective RORc inverse agonists as potential treatments of inflammatory diseases such as psoriasis and rheumatoid arthritis. Using the previously reported tertiary sulfonamide 1 as a starting point, we engineered structural modifications that significantly improved human and rat metabolic stabilities while maintaining a potent and highly selective RORc inverse agonist profile. The most advanced ?-sultam compound, GNE-3500 (27, 1-{4-[3-fluoro-4-((3S,6R)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperazin-1-yl}-ethanone), possessed favorable RORc cellular potency with 75-fold selectivity for RORc over other ROR family members and >200-fold selectivity over 25 additional nuclear receptors in a cell assay panel. The favorable potency, selectivity, in vitro ADME properties, in vivo PK, and dose-dependent inhibition of IL-17 in a PK/PD model support the evaluation of 27 in preclinical studies. PMID:26061388

  2. Spectroscopic (FT-IR, FT-Raman) investigations and quantum chemical calculations of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-{3-[4-(3-methoxyphenyl)piperazin-1-yl]propyl}-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione

    NASA Astrophysics Data System (ADS)

    Renjith, R.; Mary, Y. Sheena; Panicker, C. Yohannan; Varghese, Hema Tresa; Pakosi?ska-Parys, Magdalena; Van Alsenoy, C.; Al-Saadi, Abdulaziz A.

    2014-08-01

    The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-{3-[4-(3-methoxyphenyl) piperazin-1-yl]propyl}-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione have been investigated experimentally and theoretically using Gaussian09 software package. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. Gauge-including atomic orbital 1H NMR chemical shifts calculations were carried out and compared with experimental data. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. Molecular Electrostatic Potential was performed by the DFT method and the infrared and Raman intensities have also been reported. First hyperpolarizability is calculated in order to find its role in non-liner optics. The calculated geometrical parameters (SDD) are in agreement with that of similar derivatives. Mulliken’s net charges have been calculated and compared with the atomic natural charges.

  3. Gas solubility of H 2S and CO 2 in aqueous solutions of N-methyldiethanolamine

    Microsoft Academic Search

    P. J. G. Huttenhuis; N. J. Agrawal; J. A. Hogendoorn; G. F. Versteeg

    2007-01-01

    Alkanolamine processes are used in the industry to remove acid gases, like CO2, H2S and other sulphur components, from natural gas and industrial gas streams. In this process the acid components react with the basic alkanolamine solution via an exothermic, reversible reaction in a gas\\/liquid absorber. The composition of these amine solutions is continuously changed to optimise the (selective) removal

  4. The removal of carbon dioxide with activated solutions of methyl-diethanol-amine

    Microsoft Academic Search

    S. van Loo; E. P. van Elk; G. F. Versteeg

    2007-01-01

    The (bulk) removal of carbon-dioxide (CO2) from industrial gases, e.g. natural gas, is usually realized with a reactive absorption technique in which (non-)aqueous solutions of alkanolamines are used.From the absorption rate point of view, primary or secondary amines are preferred. However, in case the costs of regeneration are also taken into account, tertiary amines are much more attractive. In order

  5. The removal of carbon dioxide with activated solutions of methyl-diethanol-amine

    Microsoft Academic Search

    S. van Loo; E. P. van Elk; G. F. Versteeg

    The (bulk) removal of carbon-dioxide (CO2) from industrial gases, e.g. natural gas, is usually realized with a reactive absorption technique in which (non-)aqueous solutions of alkanolamines are used. From the absorption rate point of view, primary or secondary amines are preferred. However, in case the costs of regeneration are also taken into account, tertiary amines are much more attractive. In

  6. Determination of rate constants for the reaction between methyldiethanolamine and carbon dioxide 

    E-print Network

    Brabson, Charles Meade

    1985-01-01

    . These impurities are removed in a process called gas sweetening. While many processes could theoretically be used to purify natural gas, the most economical results are obtained by absorbing the impurities into liquids. In the natural gas industry, aqueous..., and energy costs available during that period. However, the energy and inflation problems of the 1970'. s and 1980's have had a significant impact on gas sweetening technology. As natural gas prices increased, and the production rates from sweet gas fields...

  7. Micelles of enzymatically synthesized PEG-poly(amine-co-ester) block copolymers as pH-responsive nanocarriers for docetaxel delivery.

    PubMed

    Zhang, Xiaofang; Liu, Bo; Yang, Zhe; Zhang, Chao; Li, Hao; Luo, Xingen; Luo, Huiyan; Gao, Di; Jiang, Qing; Liu, Jie; Jiang, Zhaozhong

    2014-03-01

    A series of PEGylated poly(amine-co-ester) terpolymers were successfully synthesized in one step via lipase-catalyzed copolymerization of ?-pentadecalactone (PDL), diethyl sebacate (DES), and N-methyldiethanolamine (MDEA) comonomers in the presence of poly(ethylene glycol) methyl ether as a chain-terminating agent. The resultant amphiphilic poly(ethylene glycol)-poly(PDL-co-MDEA-co-sebacate) (PEG-PPMS) block copolymers consisted of hydrophilic PEG chain segments and hydrophobic random PPMS chain segments, which self-assembled in aqueous medium to form stable, nanosized micelles at physiological pH of 7.4. Upon decreasing the medium pH from 7.4 to 5.0, the copolymer micelles swell significantly due to protonation of the amino groups in the micelle PPMS cores. Correspondingly, docetaxel (DTX)-encapsulated PEG2K-PPMS copolymer micelles showed gradual sustained drug release at pH of 7.4, but remarkably accelerated DTX release at acidic pH of 5.0. The drug-loaded micelle particles were readily internalized by SK-BR-3 cancer cells and, compared to free DTX drug, DTX-loaded micelles of the copolymers with optimal compositions exhibited enhanced potency against the cells. Biodegradable PEG-PPMS copolymer micelles represent a new type of promising, pH-responsive nanocarriers for anticancer drug delivery, and the drug release rate from the micelles can be systematically controlled by both pH and the copolymer composition. PMID:24398083

  8. 21 CFR 520.2380d - Thiabendazole, piperazine citrate suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...strongyles, pinworms, Strongyloides and ascarids (including members of the genera Strongylus spp., Cyathostomum spp., Cylicobrachytus spp. and related genera Craterostomum spp., Oesophagodontus spp., Poteriostomum spp., Oxyuris...

  9. 21 CFR 520.2380f - Thiabendazole, piperazine phosphate powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...oral dose. Administer as a drench or by stomach tube suspended in 1 pint of warm water...bears directions for administration by stomach tube or drench, it shall also bear the...veterinarian;” if not labeled for use by stomach tube or drench, the label shall bear...

  10. 21 CFR 520.2380f - Thiabendazole, piperazine phosphate powder.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...oral dose. Administer as a drench or by stomach tube suspended in 1 pint of warm water...bears directions for administration by stomach tube or drench, it shall also bear the...veterinarian;” if not labeled for use by stomach tube or drench, the label shall bear...

  11. 21 CFR 520.2380f - Thiabendazole, piperazine phosphate powder.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...oral dose. Administer as a drench or by stomach tube suspended in 1 pint of warm water...bears directions for administration by stomach tube or drench, it shall also bear the...veterinarian;” if not labeled for use by stomach tube or drench, the label shall bear...

  12. 21 CFR 520.2380f - Thiabendazole, piperazine phosphate powder.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...oral dose. Administer as a drench or by stomach tube suspended in 1 pint of warm water...bears directions for administration by stomach tube or drench, it shall also bear the...veterinarian;” if not labeled for use by stomach tube or drench, the label shall bear...

  13. 21 CFR 520.2380d - Thiabendazole, piperazine citrate suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... See No. 050604 in § 510.600(c) of this chapter. (c) Conditions of use. (1) It is administered to horses by stomach tube or as a drench at the rate of 1 fluid ounce of suspension per 100 pounds of body weight for the control of large...

  14. 21 CFR 520.2380d - Thiabendazole, piperazine citrate suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... See No. 050604 in § 510.600(c) of this chapter. (c) Conditions of use. (1) It is administered to horses by stomach tube or as a drench at the rate of 1 fluid ounce of suspension per 100 pounds of body weight for the control of large...

  15. 21 CFR 520.2380d - Thiabendazole, piperazine citrate suspension.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... See No. 050604 in § 510.600(c) of this chapter. (c) Conditions of use. (1) It is administered to horses by stomach tube or as a drench at the rate of 1 fluid ounce of suspension per 100 pounds of body weight for the control of large...

  16. Development of an analytical technique and construction of an apparatus to study the reaction between carbon dioxide and methyldiethanolamine

    E-print Network

    Robbins, Gary Don

    1984-01-01

    analyzed with a gas chromatographic (GC) technique developed as a part of this work. The GC analysis could be performed in lees than 8 minutes and comparison of the results from tbe GC technique with a classical wet chemistry titration showed excellent... with Alkanolamines . . 15 APPARATUS AND PROCEDURB. . . 27 Description of Experimental Apparatus. Measurement and Analytical Procedures. Operating Procedures Development of GC Analytical Technique DISCUSSION AND PRESENTATION OF RBSULTS. ~ ~ Development of Rate...

  17. Development of an analytical technique and construction of an apparatus to study the reaction between carbon dioxide and methyldiethanolamine 

    E-print Network

    Robbins, Gary Don

    1984-01-01

    at the -wellhead )ustified only rule of thumb design techniques. The energy and inflation problems of the 1970's and 1 980 's have had a significant impact on amine sweetening technology. First, as the price of natural gas increashd and production rates from... to as acid gases and are removed in a process called gas sweetening. PURIFICATION OP NATURAL GAS Theoretically, a numbez of processes could be used to remove these acid gases from raw natural gas. However, absorption by liquid solutions generally...

  18. Synthesis, characterization and antibacterial properties of dihydroxy quaternary ammonium salts with long chain alkyl bromides.

    PubMed

    Liu, Wen-Shuai; Wang, Chun-Hua; Sun, Ju-Feng; Hou, Gui-Ge; Wang, Yu-Peng; Qu, Rong-Jun

    2015-01-01

    Five N-methyl-N-R-N,N-bis(2-hydroxyethyl) ammonium bromides (R = -benzyl (chloride, BNQAS), -dodecyl (C12QAS), -tetradecyl (C14QAS), -hexadecyl (C16QAS), -octadecyl (C18QAS)) were prepared based on N-methyldiethanolamine (MDEA) and halohydrocarbon. Five QAS were characterized by FTIR, NMR, and MS. BNQAS, C12QAS, C14QAS, and C16QAS were confirmed by X-ray single-crystal diffraction. Their antibacterial properties indicated good antibacterial abilities against E. coli, S. aureus, B. subtilis, especially C12QAS with the best antibacterial ability (100% to E. coli, 95.65% to S. aureus, and 91.41% to B. subtilis). In addition, C12QAS also displayed the best antifungal activities than BNQAS and C18QAS against Cytospora mandshurica, Botryosphaeria ribis, Physalospora piricola, and Glomerella cingulata with the ratio of full marks. The strategy provides a facile way to design and develop new types of antibacterial drugs for application in preventing the fruit rot, especially apple. PMID:25215430

  19. Rigorous modeling of the acid gas heat of absorption in alkanolamine solutions

    SciTech Connect

    Emilie Blanchon le Bouhelec; Pascal Mougin; Alain Barreau; Roland Solimando [Institut Francais du Petrole, Rueil-Malmaison (France). Departement Thermodynamique et Modelisation Moleculaire

    2007-08-15

    In this work, we are interested in the estimation of CO{sub 2} and H{sub 2}S heats of absorption in aqueous solutions of alkanolamine: monoethanolamine (MEA), diethanolamine (DEA), and methyldiethanolamine (MDEA). Two methods can be used to calculate the heat release during the absorption phenomenon. The easier which consists of applying the integration of the Gibbs-Helmholtz expression remains inaccurate. The second one, more rigorous, evaluates the heat transfer through an internal energy balance for an open system. The balance expression contains partial molar enthalpies of species in the liquid phase which are calculated from the electrolyte nonrandom-two-liquid (NRTL) excess Gibbs energy model. The calculations carried out in this method can be considered as predictive regarding the NRTL model because its interaction parameters were previously and solely fitted on vapor-liquid equilibrium (VLE) data and not on experimental heat of absorption data. The comparison between both methods and experimental data for the three alkanolamines shows the contribution of this rigorous calculation to better estimate both properties (i.e., solubility and heat) and its usefulness to improve processes. Heats of absorption calculated with the second method can be used in addition to VLE data to fit NRTL parameters. This procedure leads to less-correlated parameters and allows extrapolating the model with more confidence. 63 refs., 10 figs., 6 tabs.

  20. Performance characteristics and modeling of carbon dioxide absorption by amines in a packed column

    SciTech Connect

    Lin, S.H.; Shyu, C.T. (Yuan Ze Univ., Taoyuan (Taiwan, Province of China). Dept. of Chemical Engineering)

    1999-01-01

    Carbon dioxide (CO[sub 2]) is widely recognized as a major greenhouse gas contributing to global warming. To mitigate the global warming problem, removal of CO[sub 2] from the industrial flue gases is necessary. Absorption of carbon dioxide by amines in a packed column was experimentally investigated. The amines employed in the present study were the primary mono-ethanolamine (MEA) and tertiary N-methyldiethanolamine (MDEA), two very popular amines widely used in the industries for gas purification. The CO[sub 2] absorption characteristics by these two amines were experimentally examined under various operating conditions. A theoretical model was developed for describing the CO[sub 2] absorption behavior. Test data have revealed that the model predictions and the observed CO[sub 2] absorption breakthrough curves agree very well, validating the proposed model. Preliminary regeneration tests of exhausted amine solution were also conducted. The results indicated that the tertiary amine is easier to regenerate with less loss of absorption capacity than the primary one.

  1. 40 CFR 721.10102 - Diphosphoric acid, compd. with piperazine (1:1).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...are: (i) Industrial, commercial, and consumer activities . Requirements as specified in § 721.80(j) (flame retardant). (ii) [Reserved] (b) Specific requirements . The provisions of subpart A of this part apply to...

  2. 21 CFR 520.1802b - Piperazine-carbon disulfide complex boluses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...debilitated or anemic animals is contraindicated. Do not administer to animals that are or were recently affected with colic, diarrhea, or infected with a serious infectious disease. As with most anthelmintics, drastic cathartics or other...

  3. 21 CFR 520.1802b - Piperazine-carbon disulfide complex boluses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...debilitated or anemic animals is contraindicated. Do not administer to animals that are or were recently affected with colic, diarrhea, or infected with a serious infectious disease. As with most anthelmintics, drastic cathartics or other...

  4. Thermodynamics of carbon dioxide in aqueous piperazine/potassium carbonate systems at stripper conditions

    E-print Network

    Rochelle, Gary T.

    titration of barium carbonate precipitation. The amount of amine was determined through a standard monotonic endpoint titration with 0.1 N sulfuric acid. During the experiment, the circulating vapor was dried prior

  5. A Novel Substituted Piperazine, CM156, Attenuates the Stimulant and Toxic Effects of Cocaine in Mice

    PubMed Central

    Xu, Yan-Tong; Kaushal, Nidhi; Shaikh, Jamaluddin; Wilson, Lisa L.; Mésangeau, Christophe; McCurdy, Christopher R.

    2010-01-01

    Cocaine is a highly abused drug without effective pharmacotherapies to treat it. It interacts with sigma (?) receptors, providing logical targets for the development of medications to counteract its actions. Cocaine causes toxic and stimulant effects that can be categorized as acute effects such as convulsions and locomotor hyperactivity and subchronic effects including sensitization and place conditioning. In the present study, 3-(4-(4-cyclohexylpiperazin-1-yl)butyl)benzo[d]thiazole-2(3H)-thione (CM156), a novel compound, was developed and tested for interactions with ? receptors using radioligand binding studies. It was also evaluated against cocaine-induced effects in behavioral studies. The results showed that CM156 has nanomolar affinities for each of the ? receptor subtypes in the brain and much weaker affinities for non-? binding sites. Pretreatment of male Swiss-Webster mice with CM156, before administering either a convulsive or locomotor stimulant dose of cocaine, led to a significant attenuation of these acute effects. CM156 also significantly reduced the expression of behavioral sensitization and place conditioning evoked by subchronic exposure to cocaine. The protective effects of CM156 are consistent with ? receptor-mediated actions. Together with previously reported findings, the data from CM156 and related ? compounds indicate that ? receptors can be targeted to alleviate deleterious actions of cocaine. PMID:20100904

  6. 21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ). (2) Limitations. Aqueous solution: administer by stomach tube or drench 1 fluid ounce per 100 pounds of body weight. Reconstituted soluble powder: administer by stomach tube 1 fluid ounce per 125 pounds of body weight. If...

  7. 21 CFR 520.2520g - Trichlorfon, phenothiazine, and piperazine dihydrochloride powder.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...Oxyuris equi ). (3) Limitations. Mix powder and vial contents together in warm water to form suspension. Administer by stomach tube. Do not fast horses before or after treatment. Treatment of mares in late pregnancy is not recommended....

  8. 21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ). (2) Limitations. Aqueous solution: administer by stomach tube or drench 1 fluid ounce per 100 pounds of body weight. Reconstituted soluble powder: administer by stomach tube 1 fluid ounce per 125 pounds of body weight. If...

  9. 21 CFR 520.763c - Dithiazanine iodide and piperazine citrate suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...Severely debilitated animals should not be wormed except on the advice of a veterinarian. If the drug is for administration by stomach tube, it shall be labeled: “Federal law restricts this drug to use by or on the order of a licensed veterinarian.”...

  10. 21 CFR 520.763c - Dithiazanine iodide and piperazine citrate suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...Severely debilitated animals should not be wormed except on the advice of a veterinarian. If the drug is for administration by stomach tube, it shall be labeled: “Federal law restricts this drug to use by or on the order of a licensed veterinarian.”...

  11. 21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ). (2) Limitations. Aqueous solution: administer by stomach tube or drench 1 fluid ounce per 100 pounds of body weight. Reconstituted soluble powder: administer by stomach tube 1 fluid ounce per 125 pounds of body weight. If...

  12. 21 CFR 520.1802a - Piperazine-carbon disulfide complex suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...strongyles, large strongyles (Strongyles spp.), and pinworms (Oxyuris equi ).1 (3) Limitations. Administer by stomach tube or dose syringe after withholding feed overnight or for 8 to 10 hours. Provide water as usual. Resume...

  13. 21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ). (2) Limitations. Aqueous solution: administer by stomach tube or drench 1 fluid ounce per 100 pounds of body weight. Reconstituted soluble powder: administer by stomach tube 1 fluid ounce per 125 pounds of body weight. If...

  14. 21 CFR 520.763c - Dithiazanine iodide and piperazine citrate suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...Severely debilitated animals should not be wormed except on the advice of a veterinarian. If the drug is for administration by stomach tube, it shall be labeled: “Federal law restricts this drug to use by or on the order of a licensed veterinarian.”...

  15. 21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ). (2) Limitations. Aqueous solution: administer by stomach tube or drench 1 fluid ounce per 100 pounds of body weight. Reconstituted soluble powder: administer by stomach tube 1 fluid ounce per 125 pounds of body weight. If...

  16. 21 CFR 520.763c - Dithiazanine iodide and piperazine citrate suspension.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...Severely debilitated animals should not be wormed except on the advice of a veterinarian. If the drug is for administration by stomach tube, it shall be labeled: “Federal law restricts this drug to use by or on the order of a licensed veterinarian.”...

  17. 21 CFR 520.1802a - Piperazine-carbon disulfide complex suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...strongyles, large strongyles (Strongyles spp.), and pinworms (Oxyuris equi ).1 (3) Limitations. Administer by stomach tube or dose syringe after withholding feed overnight or for 8 to 10 hours. Provide water as usual. Resume...

  18. 21 CFR 520.1802a - Piperazine-carbon disulfide complex suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...strongyles, large strongyles (Strongyles spp.), and pinworms (Oxyuris equi ).1 (3) Limitations. Administer by stomach tube or dose syringe after withholding feed overnight or for 8 to 10 hours. Provide water as usual. Resume...

  19. 21 CFR 520.2520g - Trichlorfon, phenothiazine, and piperazine dihydrochloride powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...Oxyuris equi ). (3) Limitations. Mix powder and vial contents together in warm water to form suspension. Administer by stomach tube. Do not fast horses before or after treatment. Treatment of mares in late pregnancy is not recommended....

  20. Tetra­aqua­bis­(piperazin-1-ium)cobalt(II) bis­(sulfate) dihydrate

    PubMed Central

    Sahbani, Thameur; Smirani Sta, Wajda; Rzaigui, Mohamed

    2013-01-01

    In the centrosymmetric title compound, [Co(C4H11N2)2(H2O)4](SO4)2·2H2O, the CoII atom is coordinated in a distorted octa­hedral geometry by four water O atoms and two piperazinium N atoms. These four water O atoms define an equatorial plane with a maximum deviation of 0.0384?(1)?Å while the two piperazinium N atoms complete the octa­hedron in the axial positions. Neighboring complex mol­ecules and sulfate anions are connected through an extensive network of N—H?O and O—H?O hydrogen bonds, which link the different chemical species into layers in the ab plane. Additional Owater—H?O hydrogen bonds involving the non-coordinating water mol­ecules and C—H?O inter­actions connect these layers into a three-dimensional supra­molecular structure. PMID:24454163

  1. 21 CFR 520.1805 - Piperazine phosphate with thenium closylate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... For removal of immature (fourth stage larvae) and adult hookworms (Ancylostoma caninum, A. braziliense, and Uncinaria...pups, or pups under 5 weeks of age. Maximum efficacy against hookworms necessitates two doses in 1 day of treatment....

  2. 21 CFR 520.1805 - Piperazine phosphate with thenium closylate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... For removal of immature (fourth stage larvae) and adult hookworms (Ancylostoma caninum, A. braziliense, and Uncinaria...pups, or pups under 5 weeks of age. Maximum efficacy against hookworms necessitates two doses in 1 day of treatment....

  3. 21 CFR 520.1805 - Piperazine phosphate with thenium closylate tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... For removal of immature (fourth stage larvae) and adult hookworms (Ancylostoma caninum, A. braziliense, and Uncinaria...pups, or pups under 5 weeks of age. Maximum efficacy against hookworms necessitates two doses in 1 day of treatment....

  4. 21 CFR 520.1802b - Piperazine-carbon disulfide complex boluses.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...Do not administer to animals that are or were recently affected with colic, diarrhea, or infected with a serious infectious disease. As with most anthelmintics, drastic cathartics or other gastrointestinal irritants should not be...

  5. 21 CFR 520.2520g - Trichlorfon, phenothiazine, and piperazine dihydrochloride powder.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2520g Trichlorfon...treatment. Treatment of mares in late pregnancy is not recommended. Surgery or any severe stress should be avoided for at least 2...

  6. 21 CFR 520.2520g - Trichlorfon, phenothiazine, and piperazine dihydrochloride powder.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2520g Trichlorfon...treatment. Treatment of mares in late pregnancy is not recommended. Surgery or any severe stress should be avoided for at least 2...

  7. 21 CFR 520.2520g - Trichlorfon, phenothiazine, and piperazine dihydrochloride powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2520g Trichlorfon...treatment. Treatment of mares in late pregnancy is not recommended. Surgery or any severe stress should be avoided for at least 2...

  8. Molecular design and synthesis of 1,4-disubstituted piperazines as ?(1)-adrenergic receptor blockers.

    PubMed

    Abou El-Ella, Dalal A; Hussein, Mohammed M; Serya, Rabah A T; Abdel Naby, Rana M; Al-Abd, Ahmed M; Saleh, Dalia O; El-Eraky, Wafaa I; Abouzid, Khaled A M

    2014-06-01

    A new series of 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid amide and 3,5,6,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-one derivatives were designed, synthesized, their binding and functional properties as ?1-adrenoreceptors blockers were evaluated. A new validated ?1-adrenoreceptor blocker pharmacophore model (hypothesis) was generated using Discovery Studio 2.5. The compare-fit study for the designed molecules with the generated hypothesis was fulfilled and several compounds showed significant high fit values. Compounds IVa-c, VIIa-d, VIIIa-c, Xa-c, XIa-d have shown blocking activity ranging from 46.73% up to 94.74% compared to 99.17% for prazosin. PMID:24727279

  9. Laser direct-write microfabrication and patterning

    NASA Astrophysics Data System (ADS)

    Yuan, Dajun

    The ability to generate small structures is central to modern science and technology. In this work, four laser direct-write microfabrication and micropatterning techniques were studied: (a) Laser micromachining of channels in PMMA using a CO2 laser was investigated experimentally and theoretically. Heat transfer models for the channel depth, channel profile, laser power and scanning speed were developed and applied in this work. These models, are in excellent agreement with experimental results, with a maximum deviation of approximately 5% for the range of experimental parameters (laser power, scanning speed) tested. (b) A sub-micrometer resolution laser direct-write polymerization system for 1 creating two-dimensional and three-dimensional structures was developed using a frequency-doubled Nd:YAG laser. Experimental studies and Monte Carlo simulations were conducted to understand the detailed microscale optical scattering, chemical reaction, polymerization, and their influence on critical fabrication parameters. The experimental data are in good agreement with the theoretical model. (c) Direct laser interference was developed for rapid and large area fabrication of two-dimensional and three dimensional periodic structures on photopolymerizable materials with 10ns pulses from a frequency-tripled Nd:YAG laser emitting at 355 nm. Three different photopolymerizable materials were investigated: pentaerythritol triacrylate (PETIA) with photoinitiator N-methyldiethanolamine (N-MDEA); SU-8 with absorber TINUVIN 384-2; and Shipley 1813. (d) A new approach to fabricating nanometer sized cavity arrays on Poly(3,4-ethylene dioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) thin films using laser-assisted near-field patterning was investigated. Periodic nano-cavity arrays were patterned by combining direct laser interference technology and laser induced near-field technology. An analytical model based on Mie theory was developed, the predicted intensity distributions on the substrate indicate a strong near-field enhancement confined to a very small area (nanometer scale).

  10. Influence of fluorocarbon flat-membrane hydrophobicity on carbon dioxide recovery.

    PubMed

    Lin, Su-Hsia; Tung, Kuo-Lun; Chang, Hao-Wei; Lee, Kueir-Rarn

    2009-06-01

    The influence of hydrophobicity in flat-plate porous poly(vinylidene fluoride) (PVDF) and expended polytetrafluoroethylene (PTFE) membranes on CO(2) recovery using aqueous solutions of piperazine (PZ) and alkanolamine is examined. Experiments were conducted at various gas flow rates, liquid flow rates, and absorbent concentrations. The CO(2) absorption flux increased with increasing gas flow rates and absorbent concentrations. When using 2-amino-2-methyl-1-propanol (AMP) or AMP+PZ aqueous solution as absorbent, this process was dominantly governed by gas film layer diffusion and membrane diffusion. The diffusion resistance of the membrane phase was only important when using N-methyldiethanolamine as the sole absorbent. The water contact angle increased initially with increasing plasma working power and reached at steady state value of 155 degrees beyond 100 W. The elemental fluorine-to-carbon ratio (F/C) and water contact angle of the PVDF membrane increased with increasing treatment time and reached a plateau after 5min of CH(4) plasma (100 W). Increases in the CO(2) absorption fluxes of 7% and 17% were observed for plasma-treated PVDF membranes in comparison to non-treated PVDF and PTFE, respectively, when using 1M AMP as absorbent. The membrane mass transfer coefficient, k(m), for plasma-treated PVDF membranes increased from 2.1 x 10(-4) to 2.5 x 10(-4)ms(-1). Membrane durability was greatly improved by CF(4) plasma treatment (100 W/5 min) and comparable to that of PTFE membranes. PMID:19289246

  11. Synthesis of 1,9-bis[glycidyloxypropyl]penta(10 perfluoroalkylmethylsiloxane)s and copolymerization with piperazine

    E-print Network

    Grunlan, Melissa A.

    [glycidyloxypropyl]penta- siloxanes (IV­VI) and copoly(carbosiloxane)s (VII­IX) were determined by 1 H, 13 C, 29 Si, and 19 F NMR a blend of properties of siloxane and fluoropolymers. Siloxanes retain their properties over a broad range's of the backbone chain. Siloxanes are frequently stable to 300­ 350 8C [16]. Above this temperature, reversion

  12. Poly[piperazine-1,4-diium [?(4)-chlorido-?(3)-chlorido-tri-?(2)-chlorido-chloridodicadmate(II)] monohydrate].

    PubMed

    Adib, Marwa; El Glaoui, Meher; Pereira da Silva, Pedro Sidonio; Ramos Silva, Manuela; Ben Nasr, Cherif

    2012-02-01

    In the title compound, {(C(5)H(14)N(2))[Cd(2)Cl(6)]·H(2)O}(n), the asymmetric unit contains one piperazinediium cation, one [Cd(2)Cl(6)](2-) anion and a water mol-ecule. The coordination geometries of the two Cd(2+) cations are distorted octa-hedral. Adjacent Cd(II) atoms are inter-connected alternately by paired chloride bridges, generating polymeric chains parallel to [010]. Neighbouring chains are connected by O-H?Cl hydrogen bonds involving the water mol-ecules, forming layers at z = n/2. The crystal packing is further stabilized by inter-molecular N-H?Cl and N-H?O hydrogen bonds, one of which is bifurcated. PMID:22346850

  13. The 5-substituted piperazine as a novel secondary pharmacophore greatly improving the physical properties of urea-based

    E-print Network

    Hammock, Bruce D.

    - pears selective for epoxides of lipids. In plants and ani- mals, many of these lipid substrates have However, the dialkyl ureas have limited solubility in Bioorganic & Medicinal Chemistry 14 (2006) 6586

  14. O2-Dependent Efficacy of Novel Piperidine- and Piperazine-Based Chalcones against the Human Parasite Giardia intestinalis

    PubMed Central

    Bahadur, Vijay; Mastronicola, Daniela; Tiwari, Hemandra Kumar; Kumar, Yogesh; Falabella, Micol; Pucillo, Leopoldo Paolo; Sarti, Paolo

    2014-01-01

    Giardia intestinalis is the most frequent protozoan agent of intestinal diseases worldwide. Though commonly regarded as an anaerobic pathogen, it preferentially colonizes the fairly oxygen-rich mucosa of the proximal small intestine. Therefore, when testing new potential antigiardial drugs, O2 should be taken into account, since it also reduces the efficacy of metronidazole, the gold standard drug against giardiasis. In this study, 46 novel chalcones were synthesized by microwave-assisted Claisen-Schmidt condensation, purified, characterized by high-resolution mass spectrometry, 1H and 13C nuclear magnetic resonance, and infrared spectroscopy, and tested for their toxicity against G. intestinalis under standard anaerobic conditions. As a novel approach, compounds showing antigiardial activity under anaerobiosis were also assayed under microaerobic conditions, and their selectivity against parasitic cells was assessed in a counterscreen on human epithelial colorectal adenocarcinoma cells. Among the tested compounds, three [30(a), 31(e), and 33] were more effective in the presence of O2 than under anaerobic conditions and killed the parasite 2 to 4 times more efficiently than metronidazole under anaerobiosis. Two of them [30(a) and 31(e)] proved to be selective against parasitic cells, thus representing potential candidates for the design of novel antigiardial drugs. This study highlights the importance of testing new potential antigiardial agents not only under anaerobic conditions but also at low, more physiological O2 concentrations. PMID:24217695

  15. O(2)-dependent efficacy of novel piperidine- and piperazine-based chalcones against the human parasite Giardia intestinalis.

    PubMed

    Bahadur, Vijay; Mastronicola, Daniela; Tiwari, Hemandra Kumar; Kumar, Yogesh; Falabella, Micol; Pucillo, Leopoldo Paolo; Sarti, Paolo; Giuffrè, Alessandro; Singh, Brajendra Kumar

    2014-01-01

    Giardia intestinalis is the most frequent protozoan agent of intestinal diseases worldwide. Though commonly regarded as an anaerobic pathogen, it preferentially colonizes the fairly oxygen-rich mucosa of the proximal small intestine. Therefore, when testing new potential antigiardial drugs, O2 should be taken into account, since it also reduces the efficacy of metronidazole, the gold standard drug against giardiasis. In this study, 46 novel chalcones were synthesized by microwave-assisted Claisen-Schmidt condensation, purified, characterized by high-resolution mass spectrometry, (1)H and (13)C nuclear magnetic resonance, and infrared spectroscopy, and tested for their toxicity against G. intestinalis under standard anaerobic conditions. As a novel approach, compounds showing antigiardial activity under anaerobiosis were also assayed under microaerobic conditions, and their selectivity against parasitic cells was assessed in a counterscreen on human epithelial colorectal adenocarcinoma cells. Among the tested compounds, three [30(a), 31(e), and 33] were more effective in the presence of O2 than under anaerobic conditions and killed the parasite 2 to 4 times more efficiently than metronidazole under anaerobiosis. Two of them [30(a) and 31(e)] proved to be selective against parasitic cells, thus representing potential candidates for the design of novel antigiardial drugs. This study highlights the importance of testing new potential antigiardial agents not only under anaerobic conditions but also at low, more physiological O2 concentrations. PMID:24217695

  16. CO2 Capture by Absorption with Potassium Carbonate

    SciTech Connect

    Gary T. Rochelle; Eric Chen; Babatunde Oyenekan; Andrew Sexton; Jason Davis; Marus Hiilliard; Qing Xu; David Van Wagener; Jorge M. Plaza

    2006-12-31

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. The best solvent and process configuration, matrix with MDEA/PZ, offers 22% and 15% energy savings over the baseline and improved baseline, respectively, with stripping and compression to 10 MPa. The energy requirement for stripping and compression to 10 MPa is about 20% of the power output from a 500 MW power plant with 90% CO{sub 2} removal. The stripper rate model shows that a ''short and fat'' stripper requires 7 to 15% less equivalent work than a ''tall and skinny'' one. The stripper model was validated with data obtained from pilot plant experiments at the University of Texas with 5m K{sup +}/2.5m PZ and 6.4m K{sup +}/1.6m PZ under normal pressure and vacuum conditions using Flexipac AQ Style 20 structured packing. Experiments with oxidative degradation at low gas rates confirm the effects of Cu{sup +2} catalysis; in MEA/PZ solutions more formate and acetate is produced in the presence of Cu{sup +2}. At 150 C, the half life of 30% MEA with 0.4 moles CO{sub 2}/mole amine is about 2 weeks. At 100 C, less than 3% degradation occurred in two weeks. The solubility of potassium sulfate in MEA solution increases significantly with CO{sub 2} loading and decreases with MEA concentration. The base case corrosion rate in 5 M MEA/1,2M PZ is 22 mpy. With 1 wt% heat stable salt, the corrosion rate increases by 50% to 160% in the order: thiosulfate< oxalate

  17. Piperazine-1,4-diium bis­(pyridine-2,6-dicarboxyl­ato-?3 O 2,N,O 6)cobaltate(II) tetra­hydrate

    PubMed Central

    Raissi Shabari, Akbar; Ghoddoosi, Nazanin; Pourayoubi, Mehrdad; Moradi, Shahram

    2011-01-01

    The asymmetric unit of the title complex, (C4H12N2)[Co(C7H3NO4)2]·4H2O, consists of one piperazinediium dication, one [Co(py-2,6-dc)2]2? dianion (where py-2,6-dc is pyridine-2,6-dicarboxyl­ate) and four water mol­ecules. The piperazinediium cation adopts a chair conformation and the CoII ion is six-coordinated in an N2O4 environment, having a distorted octa­hedral geometry. In the crystal, inter­molecular O—H?O, N—H?O and weak C—H?O hydrogen bonds link the components, forming a three-dimensional network. PMID:21836959

  18. Use of physicochemical calculation of pKa and CLogP to predict phospholipidosis-inducing potential: a case study with structurally related piperazines

    Microsoft Academic Search

    J. P. Ploemen; J. C. Kelder; T. G. M. Hafmans; H. van de Sandt; J. A. van Burgsteden; P. J. Saleminki; E. van Esch

    2004-01-01

    Several cationic amphiphilic compounds are known to induce phospholipidosis, a condition primarily characterized by excessive accumulation of phospholipids in different cell types, giving the affected cells a finely foamy appearance. Excessive storage of lamellar membranous intralysosomal inclusion bodies is the hallmark for phospholipidosis on the electron microscopic level. In case of alveolar phospholipidosis, foamy macrophages accumulate within the alveolar spaces

  19. Synthesis, antibacterial and antitubercular activities of some 7-[4-(5-amino-[1,3,4]thiadiazole-2-sulfonyl)-piperazin-1-yl] fluoroquinolonic derivatives

    Microsoft Academic Search

    S. Talath; A. K. Gadad

    2006-01-01

    In the present study, a series of 7-[4-(5-amino-1,3,4 thiadiazole-2-sulfonyl)]-1-piperazinyl fluoroquinolonic derivatives VIIa–d were synthesized in good yields and characterized by IR, 1H-NMR, 13C-NMR, FAB Mass spectral and elemental analyses. The compounds were evaluated for their preliminary in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria and selected compounds VIIa, b were screened for antitubercular activity against Mycobacterium tuberculosis H37Rv

  20. Cytotoxic activities of hydroxyethyl piperazine-based ? receptor ligands on cancer cells alone and in combination with melphalan, PB28 and haloperidol.

    PubMed

    Korpis, K; Weber, F; Wünsch, B; Bednarski, P J

    2014-12-01

    ? Receptor ligands are attracting interest as possible anti-cancer agents because of their ability to induce cell death by different mechanisms. In this study we investigated the cytotoxic effects of 12 recently developed ?-receptor ligands in a panel of eight different human tumor cell lines by either the crystal violet or MTT assays. The results show that ? ligands have broad cytotoxic activity on a number of human cancer cell lines with IC50 values in the low ?M range. In addition, apoptosis was observed by the annexin-V/PI double staining method when RPMI 8226 human multiple myeloma cells were treated with a representative ? ligand, (R)-2b. Combination of (R)-2b with melphalan led to a higher apoptotic rate than with the drug alone. Likewise, combined treatment of (R)-2b with the known high affinity ?2-agonist PB28 showed an additive effect on the induction of apoptosis in the RPMI 8226 line. In contrast, combinations of (R)-2b with the known ?1-antagonist haloperidol lead to a significant reduction in the cytotoxic activity of (R)-2b. These results support the idea that (R)-2b acts as a ?-agonist to cause the death of RPMI 8226 cells. PMID:25951666

  1. Threaded structure and blue luminescence of (CuCN)20(Piperazine)7{ Robert D. Pike,* Kathryn E. deKrafft, Amanda N. Ley and Tristan A. Tronic

    E-print Network

    Pike, Robert D.

    Krafft, Amanda N. Ley and Tristan A. Tronic Received (in CCAUS) 21st May 2007, Accepted 20th June 2007 First interpenetrating sub-lattices. Cu atoms large circles, orange = sublattice A atoms and green = sublattice B atoms

  2. Carbonic anhydrase promotes the absorption rate of CO2 in post-combustion processes.

    PubMed

    Vinoba, Mari; Bhagiyalakshmi, Margandan; Grace, Andrews Nirmala; Kim, Dae Hoon; Yoon, Yeoil; Nam, Sung Chan; Baek, Il Hyun; Jeong, Soon Kwan

    2013-05-01

    The rate of carbon dioxide (CO2) absorption by monoethanol amine (MEA), diethanol amine (DEA), N-methyl-2,2'-iminodiethanol (MDEA), and 2-amino-2-methyl 1-propanol (AMP) solutions was found to be enhanced by the addition of bovine carbonic anhydrase (CA), has been investigated using a vapor-liquid equilibrium (VLE) device. The enthalpy (-?Habs) of CO2 absorption and the absorption capacities of aqueous amines were measured in the presence and/or absence of CA enzyme via differential reaction calorimeter (DRC). The reaction temperature (?T) under adiabatic conditions was determined based on the DRC analysis. Bicarbonate and carbamate species formation mechanisms were elucidated by (1)H and (13)C NMR spectral analysis. The overall CO2 absorption rate (flux) and rate constant (kapp) followed the order MEA > DEA > AMP > MDEA in the absence or presence of CA. Hydration of CO2 by MDEA in the presence of CA directly produced bicarbonate, whereas AMP produced unstable carbamate intermediate, then underwent hydrolytic reaction and converted to bicarbonate. The MDEA > AMP > DEA > MEA reverse ordering of the enhanced CO2 flux and kapp in the presence of CA was due to bicarbonate formation by the tertiary and sterically hindered amines. Thus, CA increased the rate of CO2 absorption by MDEA by a factor of 3 relative to the rate of absorption by MDEA alone. The thermal effects suggested that CA yielded a higher activity at 40 °C. PMID:23621860

  3. Synthesis of new piperazine derived Cu(II)/Zn(II) metal complexes, their DNA binding studies, electrochemistry and anti-microbial activity: Validation for specific recognition of Zn(II) complex to DNA helix by interaction with thymine base

    NASA Astrophysics Data System (ADS)

    Bhat, Irshad-ul-Haq; Tabassum, Sartaj

    2009-06-01

    New 3,4:9,10-dibenzo-2,11-dihydroxy-1,12-bispiperazine-5,8-dioxododecane complexes [C 24H 36N 4O 6Cu] ( 1), [C 24H 32N 4O 4Zn] ( 2) have been synthesized and characterized by elemental analysis, IR, NMR, Mass, EPR, UV-vis spectroscopy and molar conductance measurements. The complexes are non-ionic in nature and possess octahedral geometry around Cu 2+, Zn 2+ central metal ions. The binding studies of 1 and 2 with calf thymus DNA (CT-DNA) were investigated by UV-vis, fluorescence, cyclic voltammetery and viscosity measurements. The calculated binding constant Kb for 1 and 2 obtained from UV-vis absorption studies was 7.6 × 10 3 M -1, 80.8 × 10 4 M -1, respectively. The intrinsic binding constants were also estimated to be 7.0 × 10 4 M -1 and 7.53 × 10 5 M -1 for 1 and 2, respectively by using emission titrations. These experimental results suggest that complexes are groove binders and interact to CT-DNA with different affinities. Both the complexes in presence and absence of CT-DNA show quasireversible wave corresponding to Cu II/Cu I and Zn II/Zn I redox couple. The changes in E1/2, ? E, Ipa/ Ipc ascertain the interaction of 1 and 2 with CT-DNA. Further, decrease in viscosity of CT-DNA with increasing concentration of complexes was observed. In vitro, antimicrobial activity against fungi A. brassicicola, A. niger and bacteria E. coli, P. aeruginosa of complexes were carried out, which indicate that complex 2 is more active against both fungal and bacterial strains as shown by % inhibition data.

  4. technology offer Vienna University of Technology | Research and Transfer Support | Hildegard Sieberth

    E-print Network

    Szmolyan, Peter

    | Vardenafil-, Sildenafil-, Tadalafil analogs | chiral piperazine analogs Selective phosphodiesterase (PDE5 dysfunction, like Sildenafil, Vardenafil and Tadalafil. The known PDE5 inhibitors all contain a common

  5. technology offer Vienna University of Technology | Research and Transfer Support | Claudia Doubek

    E-print Network

    Szmolyan, Peter

    | Vardenafil-, Sildenafil-, Tadalafil analogs | chiral piperazine analogs Selective phosphodiesterase (PDE5 dysfunction, like Sildenafil, Vardenafil and Tadalafil. The known PDE5 inhibitors all contain a common

  6. Studies on the metabolism and the toxicological analysis of the nootropic drug fipexide in rat urine using gas chromatography–mass spectrometry

    Microsoft Academic Search

    Roland F. Staack; Hans H. Maurer

    2004-01-01

    Qualitative studies are described on the metabolism and the toxicological analysis of the nootropic fipexide (FIP) in rat urine using gas chromatography–mass spectrometry (GC–MS). FIP was extensively metabolized to 1-(3,4-methylenedioxybenzyl)piperazine (MDBP), 4-chlorophenoxyacetic acid, 1-[2-(4-chlorophenoxy)acetyl]piperazine, N-(4-hydroxy-3-methoxy-benzyl)piperazine, piperazine, N-(3,4-methylenedioxybenzyl)ethylenediamine, and N-[2-(4-chlorophenoxy)acetyl]ethylenediamine. The authors’ systematic toxicological analysis (STA) procedure using full-scan GC–MS after acid hydrolysis of one urine aliquot, liquid-liquid extraction and acetylation

  7. Factors affecting the photoyellowing which occurs during the photoinitiated polymerization of acrylates

    Microsoft Academic Search

    Nergis Arsu; R. Stephen Davidson; Richard Holman

    1995-01-01

    The influence of the type of photoinitiator, type of polymerizable reactive diluent and added amine synergist on the yellowing which occurs during the curing of clear films is examined. Type I photoinitiators based on acetophenone give rise to the least yellowing. The presence of amines, such as N-methyldiethanolamine, increases yellowing to a noticeable extent. Amino groups present in the initiator

  8. Solvent changeouts without plant shutdown

    SciTech Connect

    Vickery, D.J.; Campbell, S.W. (Taylor, Weiland and Associates, Inc., Potsdam, NY (US))

    1988-01-01

    For reasons of greater selectivity, lower regeneration energy requirements, reduced corrosivity and possible greater amine stability, MDEA continues to replace DEA in numerous selective H/sub 2/S removal applications. Solvent changeouts from DEA to MDEA often require no equipment modification, yet they are generally achieved by shutting down the plant, draining the old solvent, cleaning, and finally recharging with MDEA. However, in at least one plant, solvent changeout was done on the fly simply by periodically making up normal DEA losses with MDEA until the plant was finally operating on MDEA alone. Gradual solvent changeouts have the advantages of no lost production, no disposal problems with the environmentally-hazardous old solvent, no use and subsequent disposal of cleaning agents, and no additional manpower requirements. An advanced flowsheet simulation capability can suggest when such a procedure is feasible and, when it is, plant simulation can help to ensure that the solvent changeout is done reliably and with no production or cost penalties. GASPLANT-PLUS(TM) is currently the only commercial simulator having formulated solvent (mixed amine) capabilities within a fully flexible flowsheeting environment. After highlighting its technical foundations, they will compare GASPLANT-PLUS predictions with some commercial plant data and, through examples, they will show how solvent changeouts can be done gradually, without plant shutdown.

  9. Research of a PVA composite ultrafiltration membrane used in oil-in-water

    Microsoft Academic Search

    Ying Shang; Yuelian Peng

    2007-01-01

    A composite ultrafiltration membrane with a thin hydrophilic-layer was prepared by interfacial polymerization of poly(vinyl alcohol) (PVA), piperazine and terephthalyl chloride on the polyether sulfone (PES) support membrane. The effects of the ratio of two monomers, piperazine and terephthalyl chloride, the concentration of SDS, sodium carbonate and polyvinyl alcohol (PVA) were investigated on the best composite membrane performances. Infrared spectra

  10. Chukwuemeka I. Okoye Carbon Dioxide Solubility and Absorption Rate in

    E-print Network

    Rochelle, Gary T.

    Copyright by Chukwuemeka I. Okoye 2005 #12;Carbon Dioxide Solubility and Absorption Rate _______________________ Nicholas A. Peppas #12;Carbon Dioxide Solubility and Absorption Rate in Monoethanolamine/Piperazine/H2O for. #12;iii Carbon Dioxide Solubility and Absorption Rate in Monoethanolamine/Piperazine/H2O

  11. Synthesis of 2-methylpiperazine by photocatalytic reaction in a non-aqueous suspension of semiconductor-zeolite composite catalysts.

    PubMed

    Subba Rao, Kambala V; Subrahmanyam, Machiraju

    2002-08-01

    UV irradiation onto a non-aqueous suspension of semiconductor-zeolite composite catalysts with N-(beta-hydroxypropyl)ethylenediamine (N-beta-HPEDA) produces 2-methylpiperazine and piperazine. The yield of 2-methylpiperazine and piperazine depends on the type of semiconductor and zeolite. A 5 wt% TiO2-Hbeta composite photocatalyst shows highest yield of 2-methylpiperazine. PMID:12659504

  12. Simultaneous, quantitative determination of opiates, amphetamines, cocaine and benzoylecgonine in oral fluid by liquid chromatography quadrupole-time-of-flight mass spectrometry

    Microsoft Academic Search

    Kjell A. Mortier; Kristof E. Maudens; Willy E. Lambert; Karine M. Clauwaert; Jan F. Van Bocxlaer; Dieter L. Deforce; Carlos H. Van Peteghem; André P De Leenheer

    2002-01-01

    A method using liquid chromatography coupled to tandem mass spectrometry is described for the determination of drugs of abuse in oral fluid. The method is able to simultaneously quantify amphetamines (amphetamine, methamphetamine, MDA, MDMA and MDEA), opiates (morphine and codeine), cocaine and benzoylecgonine. Only 200 ?l of oral fluid is spent for analysis. The sample preparation is easy and consists

  13. NATURAL GAS FIRED POWER CYCLES WITH INTEGRATED CO 2 CAPTURE

    Microsoft Academic Search

    Olav Bolland; Henriette Undrum; Michel Myhre-Nielsen

    This paper examines two options with natural gas fired power cycles including carbon dioxide capture. One of these is about capturing carbon dioxide by absorption using the absorbent MDEA at elevated pressure integrated in the turbine of the gas turbine. The other option is stoichiometri c combustion with pure oxygen at high pressure in a modified Rankine type cycle -

  14. Swine Pneumonia 

    E-print Network

    Lawhorn, D. Bruce

    1998-06-18

    ? for water, Tramisol? for feed [Mallinckrodt]), Safe-Guard? for feed (Hoechst-Roussel), Banmith? premix (Pfizer) and piperazine for water (Duravet) are effective dewormers for adult roundworms. Safe- Guard? is effective against some migrating larval stages...

  15. CO2 Capture by Absorption with Potassium Carbonate

    E-print Network

    Rochelle, Gary T.

    absorber. The oxidative degradation of piperazine or organic acids is reduced significantly by inhibitor A solution increases significantly with CO2 loading and decreases with MEA concentration. The base case

  16. MIXED-LIGAND COMPLEXES OF COBALT(III) WITH DITHIOCARBAMATES AND A CYCLIC TETRADENTATE SECONDARY AMINE

    Microsoft Academic Search

    Sofija P. Sovilj; Gordana Vu?kovi?; Ksenija Babi?; Tibor J. Sabo; Slobodan Macura; Nenad Jurani?

    1997-01-01

    4-Morpholine-, piperidine-, 4-piperazine- and N-methyl- piperazine-dithiocarbamate complexes of Cobalt (III) with 1, 4, 8, 11-tetraazacyclotetradecane, of general formula [Co(Rdtc)cyclam] (C104)2, have been prepared and have been characterized. The complexes adopt cis-octahedral geometry with folded macrocyclic ligand and with the dithiocarbamate bound as a bidentate. trans-influence of the dithiocarbamate ligands was studied by NMR spectroscopy and established the order piperidine-dtc >

  17. Effective eradication of pinworms ( Syphacia muris, Syphacia obvelata and Aspiculuris tetraptera ) from a rodent breeding colony by oral anthelmintic therapy

    Microsoft Academic Search

    Lionel Zenner

    1998-01-01

    Summary An oral combination of piperazine and ivermectin was used over a 6-week period for treating three different colonies of mice or rats infested with Syphacia obvelata, Syphacia muris or Aspiculuris tetraptera. No acute toxic effect was found in transgenic lines of mice or rats with these products in a preliminary trial. The colonies were treated with piperazine, 2.1 mg\\/ml

  18. Effect of selected anthelmintics on three common helminths in the brown pelican (Pelecanus occidentalis).

    PubMed

    Grimes, J; Suto, B; Greve, J H; Albers, H F

    1989-01-01

    The effect of selected anthelmintics (albendazole, fenbendazole, piperazine dihydrochloride and clorsulon) against three major helminths (Contracaecum multipapillatum, Mesostephanus appendiculatoides, and Phagicola longus) were studied in 29 brown pelicans (Pelecanus occidentalis). Albendazole and fenbendazole were highly effective against all three parasites. Clorsulon had moderate effect against M. appendiculatoides and poor effect against C. multipapillatum and P. longus. Piperazine dihydrochloride had no effect against these helminths. PMID:2915399

  19. Supporting Information Discovery of 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-

    E-print Network

    Sabatini, David M.

    S1 Supporting Information Discovery of 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl-36, 38-47 #12;S2 1-(4-(4-([3,6'-biquinolin]-4'-ylamino)-2-(trifluoromethyl)phenyl)piperazin-1-yl)-3): m/z (M+H)+ 586.94. 1-(4-(4-([3,6'-biquinolin]-4'-ylamino)-2-(trifluoromethyl)phenyl)piperazin-1-yl

  20. Synthesis and spectroscopic characterization of dicyanamido–Cu(II) complexes. Part 2 1 For Part 1 see Ref. [1]. 1 : Crystal structure of the complexes of tris[2-(2-pyridylethyl)]amine, tris(2-pyridylmethyl)amine and 1,4-bis[2-(2-pyridylethyl)]piperazine

    Microsoft Academic Search

    Franz A. Mautner; Jesse B. Soileau; Paul K. Bankole; August A. Gallo; Salah S. Massoud

    2008-01-01

    Two classes of novel dicyanamido (dca)–Cu(II) complexes were synthesized with a variety of tetradentate tripod amines, tridentate amines and diazacycloalkanes with pyridyl arms of different alkyl lengths and with tetra-aza macrocycles with different cavity sizes; the mononuclear, Cu(L)(dca)]ClO4 (L=tepa (1), TPA (2), pzdepy (4), hpzpy2 (5), cyclen (7), cyclam (8), tacp (9)) or Cu(L)(dca)ClO4 (L=MeDPA (10), Mepea (11)) and the

  1. Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase.

    PubMed

    Guagnano, Vito; Furet, Pascal; Spanka, Carsten; Bordas, Vincent; Le Douget, Mickaël; Stamm, Christelle; Brueggen, Josef; Jensen, Michael R; Schnell, Christian; Schmid, Herbert; Wartmann, Markus; Berghausen, Joerg; Drueckes, Peter; Zimmerlin, Alfred; Bussiere, Dirksen; Murray, Jeremy; Graus Porta, Diana

    2011-10-27

    A novel series of N-aryl-N'-pyrimidin-4-yl ureas has been optimized to afford potent and selective inhibitors of the fibroblast growth factor receptor tyrosine kinases 1, 2, and 3 by rationally designing the substitution pattern of the aryl ring. On the basis of its in vitro profile, compound 1h (NVP-BGJ398) was selected for in vivo evaluation and showed significant antitumor activity in RT112 bladder cancer xenografts models overexpressing wild-type FGFR3. These results support the potential therapeutic use of 1h as a new anticancer agent. PMID:21936542

  2. ABBREVIATiONS: GABAR, y-aminobutyric acid type A receptor; GABA, y-aminobutyric acid; HEPES, 4-(2-hydroxyethyl)-1 -piperazineethane-sulfonic acid; PIPES, piperazine-N,N'-bis(2-ethanesulfonic acid); DZP, diazepam; ZOL, zolpidem; I-V. current-voltage, Vh, m

    E-print Network

    Abraham, Nader G.

    , diazepam; ZOL, zolpidem; I-V. current-voltage, Vh, membrane holding potential; p-gal, f3-galactosidase; GFP- containing receptors (26 MM). a533y2L receptors were zinc and diazepam sensitive but zolpidem insensitive

  3. Synthesis and spectroscopic characterization of dicyanamido-Cu(II) complexes. Part 2 : Crystal structure of the complexes of tris[2-(2-pyridylethyl)]amine, tris(2-pyridylmethyl)amine and 1,4-bis[2-(2-pyridylethyl)]piperazine

    NASA Astrophysics Data System (ADS)

    Mautner, Franz A.; Soileau, Jesse B.; Bankole, Paul K.; Gallo, August A.; Massoud, Salah S.

    2008-10-01

    Two classes of novel dicyanamido (dca)-Cu(II) complexes were synthesized with a variety of tetradentate tripod amines, tridentate amines and diazacycloalkanes with pyridyl arms of different alkyl lengths and with tetra-aza macrocycles with different cavity sizes; the mononuclear, Cu(L)(dca)]ClO 4 (L = tepa ( 1), TPA ( 2), pzdepy ( 4), hpzpy 2 ( 5), cyclen ( 7), cyclam ( 8), tacp ( 9)) or Cu(L)(dca)ClO 4 (L = MeDPA ( 10), Mepea ( 11)) and the dinuclear, [Cu 2(L') 2(dca)](ClO 4) 3 (L' = pmap ( 3), pzpy 2 ( 6)). The isolated complexes were structurally characterized by electronic and IR spectroscopy as well as by X-ray. Single crystal X-ray diffraction analysis of the complexes [Cu(tepa)(dca)]ClO 4 ( 1), [Cu(TPA)(dca)]ClO 4 ( 2) and [Cu(pzdepy)(dca)]ClO 4 ( 4) reveal their monomeric penta-coordinate nature with the isolated [Cu(L)(dca)] + cations and ClO4- counter ions. All the complexes with the exception of 2 adapt distorted square pyramidal geometry while the coordination polyhedron around the copper center in 2 may be described as a distorted trigonal bipyramidal stereochemistry. The visible spectra of the complexes in aqueous solutions or in methanol are in complete agreement with the assigned X-ray geometry around the Cu(II) centers.

  4. Discovery of 4-(4-(2-((5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)-ethyl)piperazin-1-yl)quinolin-8-ol and its analogues as highly potent dopamine D2/D3 agonists and as iron chelator: In vivo activity indicates potential application in symptomatic and neuroprotective therapy for Parkinson’s Disease

    PubMed Central

    Ghosh, Balaram; Antonio, Tamara; Reith, Maarten E. A.; Dutta, Aloke K.

    2010-01-01

    The role of iron in the pathogenesis of Parkinson’s disease (PD) has been implicated strongly due to generation of oxidative stress leading to dopamine cell death. In our overall goal to develop bifunctional/multifunctional drugs, we designed dopamine D2/D3 agonist molecules with a capacity to bind to iron. Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate inhibition constants (Ki). Functional activity of selected compounds was carried out with GTP?S binding assay. SAR results identified compounds (+)-19a and (?)-19b as two potent agonists for both D2 and D3 receptors (EC50 (GTP?S); D2 = 4.51 and 1.69 nM and D3 = 1.58 and 0.74 nM for (?)-19b and (+)-19a, respectively). In vitro complexation studies with 19b demonstrated efficient chelation with iron. Furthermore, the deoxyribose assay with 19b demonstrated potent antioxidant activity. In PD animal model study, (?)-19b exhibited potent in vivo activity in reversing locomotor activity in reserpinized rats and also in producing potent rotational activity in 6-OHDA lesioned rats. This reports initial development of unique lead molecules which might find potential use in symptomatic and neuroprotective treatment of PD. PMID:20146482

  5. Discovery of 4-(4-(2-((5-Hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)ethyl)piperazin-1-yl)quinolin-8-ol and its analogues as highly potent dopamine D2/D3 agonists and as iron chelator: in vivo activity indicates potential application in symptomatic and neuroprotective therapy for Parkinson's disease.

    PubMed

    Ghosh, Balaram; Antonio, Tamara; Reith, Maarten E A; Dutta, Aloke K

    2010-03-11

    The role of iron in the pathogenesis of Parkinson's disease (PD) has been implicated strongly because of generation of oxidative stress leading to dopamine cell death. In our overall goal to develop bifunctional/multifunctional drugs, we designed dopamine D2/D3 agonist molecules with a capacity to bind to iron. Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptor with tritiated spiperone to evaluate inhibition constants (K(i)). Functional activity of selected compounds was carried out with GTPgammaS binding assay. SAR results identified compounds (+)-19a and (-)-19b as two potent agonists for both D2 and D3 receptors (EC(50) (GTPgammaS); D2 = 4.51 and 1.69 nM and D3 = 1.58 and 0.74 nM for (-)-19b and (+)-19a, respectively). In vitro complexation studies with 19b demonstrated efficient chelation with iron. Furthermore, the deoxyribose assay with 19b demonstrated potent antioxidant activity. In PD animal model study, (-)-19b exhibited potent in vivo activity in reversing locomotor activity in reserpinized rats and also in producing potent rotational activity in 6-OHDA lesioned rats. This reports initial development of unique lead molecules that might find potential use in symptomatic and neuroprotective treatment of PD. PMID:20146482

  6. PUTATIVE AGMATINASE INHIBITOR FOR HYPOXIC-ISCHEMIC NEW BORN BRAIN DAMAGE

    PubMed Central

    Piletz, John E.; Klenotich, Stephanie; Lee, Ken S.; Zhu, Qian Long; Valente, Edward; Collins, Michael A.; Jones, Vyvyca; Lee, Soeb Nam; Yangzheng, Feng

    2013-01-01

    Agmatine is an endogenous brain metabolite, decarboxylated arginine, which has neuroprotective properties when injected intraperitoneally (i.p.) into rat pups following hypoxic-ischemia. A previous screen for compounds based on rat brain lysates containing agmatinase with assistance from computational chemistry, led to piperazine-1-carboxamidine as a putative agmatinase inhibitor. Herein, the neuroprotective properties of piperazine-1-carboxamidine are described both in vitro and in vivo. Organotypic entorhinal-hippocampal slices were firstly prepared from seven-day-old rat pups and exposed in vitro to atmospheric oxygen depletion for 3 hrs. Upon reoxygenation the slices were treated with piperazine-1-carboxamidine or agmatine (50 ?g/ml agents), or saline, and 15 hours later propidium iodine was used to stain. Piperazine-1-carboxamidine or agmatine produced substantial in vitro protection compared to post-reoxygenated saline-treated controls. An in vivo model involved surgical right carotid ligation followed by exposure to hypoxic ischemia (8% oxygen) for 2.5 hours. Piperazine-1-carboxamidine at 50 mg/kg i.p. was given 15 minutes post-reoxygenation and continued twice daily for 3 days. Cortical agmatine levels were elevated (+28.5%) following piperazine-1-carboxamidine treatment with no change in arginine or its other major metabolites. Histological staining with anti-Neun monoclonal antibody also revealed neuroprotection of CA1–3 layers of the hippocampus. Until endpoint at 22 days of age, no adverse events were observed in treated pups' body weights, rectal temperatures, or prompted ambulation. Piperazine-1-carboxamidine therefore appears to be a neuroprotective agent of a new category, agmatinase inhibitor. PMID:23334804

  7. Putative agmatinase inhibitor for hypoxic-ischemic new born brain damage.

    PubMed

    Piletz, John E; Klenotich, Stephanie; Lee, Ken S; Zhu, Qian Long; Valente, Edward; Collins, Michael A; Jones, Vyvyca; Lee, Soeb Nam; Yangzheng, Feng

    2013-08-01

    Agmatine is an endogenous brain metabolite, decarboxylated arginine, which has neuroprotective properties when injected intraperitoneally (i.p.) into rat pups following hypoxic-ischemia. A previous screen for compounds based on rat brain lysates containing agmatinase with assistance from computational chemistry, led to piperazine-1-carboxamidine as a putative agmatinase inhibitor. Herein, the neuroprotective properties of piperazine-1-carboxamidine are described both in vitro and in vivo. Organotypic entorhinal-hippocampal slices were firstly prepared from 7-day-old rat pups and exposed in vitro to atmospheric oxygen depletion for 3 h. Upon reoxygenation, the slices were treated with piperazine-1-carboxamidine or agmatine (50 ?g/ml agents), or saline, and 15 h later propidium iodine was used to stain. Piperazine-1-carboxamidine or agmatine produced substantial in vitro protection compared to post-reoxygenated saline-treated controls. An in vivo model involved surgical right carotid ligation followed by exposure to hypoxic-ischemia (8 % oxygen) for 2.5 h. Piperazine-1-carboxamidine at 50 mg/kg i.p. was given 15 min post-reoxygenation and continued twice daily for 3 days. Cortical agmatine levels were elevated (+28.5 %) following piperazine-1-carboxamidine treatment with no change in arginine or its other major metabolites. Histologic staining with anti-Neun monoclonal antibody also revealed neuroprotection of CA1-3 layers of the hippocampus. Until endpoint at 22 days of age, no adverse events were observed in treated pups' body weights, rectal temperatures, or prompted ambulation. Piperazine-1-carboxamidine therefore appears to be a neuroprotective agent of a new category, agmatinase inhibitor. PMID:23334804

  8. Quantitative determination of amphetamines, cocaine, and opiates in human hair by gas chromatography\\/mass spectrometry

    Microsoft Academic Search

    L Skender; V Kara?i?; I Br?i?; A Bagari?

    2002-01-01

    Hair of young subjects (N=36) suspected for drug abuse was analysed for morphine, codeine, heroin, 6-acetylmorphine, cocaine, methadone, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA). The analysis of morphine, codeine, heroin, 6-acetylmorphine, cocaine, and methadone in hair included incubation in methanol, solid-phase extraction, derivatisation by the mixture of propionic acid anhydride and pyridine, and gas chromatography\\/mass spectrometry (GC\\/MS).

  9. 2-Methylol-thioxanthone as a free radical polymerization initiator

    Microsoft Academic Search

    Gokhan Temel; Nergis Arsu

    2007-01-01

    2-Methylol-thioxanthone (TX-M) was synthesized and characterized as a new photoinitiator. Photopolymerization experiments were performed with methyl methacrylate and also trimethylolpropanetriacrylate (TMPTA) as a multifunctional monomer in the presence of TX-M with N-methyl diethanol amine. Polymerization did not occur in an air atmosphere with TX-M without adding MDEA. The inhibiting effect of oxygen on the rate of polymerization was observed to

  10. Properties of segmented polyurethane zwitterionomer elastomers

    Microsoft Academic Search

    T. A. Speckhard; K. K. S. Hwang; C. Z. Yang; W. R. Laupan; S. L. Cooper

    1984-01-01

    Four series of polyurethane zwitterionomers based on different soft segment polyols [polyethylene oxide (PEO), polypropylene oxide (PPO), polytetramethylene oxide (PTMO), and polybutadiene (PBD)] were synthesized, and their properties were investigated using differential scanning calorimetry, dynamic mechanical spectroscopy, infrared dichroism, and stress-strain testing. Two different molar ratios of hard segment [4,4?-diphenylmethane diisocyanate (MDI)] to chain extender [N-methyl diethanol-amine (MDEA)] to soft

  11. Surface composition and protein adsorption of polyurethane membrane

    Microsoft Academic Search

    Shih-Liang Huang; Cheng-Fang Ou; Juin-Yih Lai

    1999-01-01

    Membranes of uncomplexed polyurethanes (PUs) were prepared by hydroxyl-terminated polybutadiene (HTPB), 4,4?-dicyclohexylmethane diisocyanate (H12MDI) and 1,4-butane diol (1,4-BD). While complexed PUs were prepared by using N-methyl diethanol (MDEA) as the chain extender of which the tertiary amines were complexed with cupric ions. Molar ratio of protein adsorption of fibrinogen to albumin (F\\/A molar ratio) on polymer surface was measured. The

  12. Epoxy resins cured with aminophenylmethylphosphine oxide—II. Mechanism of thermal decomposition

    Microsoft Academic Search

    Sergei V. Levchik; Giovanni Camino; Maria Paola Luda; Luigi Costa; George Muller; Bruno Costes

    1998-01-01

    The thermal decomposition behaviour of the mixed epoxy resin, tetraglycidyl 4,4?-diaminodiphenylmethane (TGDDM) and diglycidylether of bisphenol A (DGEBA), in a 1:1 ratio, cured with 3,3?,5,5?-tetraethyl-4,4?-diaminodiphenylmethane (M-DEA) or bis(m-aminophenyl)methylphosphine oxide (BAMPO) or with mixtures of the hardeners was studied. On heating, the resins rapidly decompose above 290 °C in an exothermic process involving dehydration, bond scission and chain fragment volatilisation. However,

  13. Drug Testing in Blood: Validated Negative-Ion Chemical Ionization Gas Chromatographic-Mass Spectrometric Assay for Enantioselective Measurement of the Designer Drugs 3,4-Methylenedioxyamphetamine, 3,4-Methylenedioxymethamphetamine (MDMA), and 3,4-Methylenedioxyethylamphetamine and Its Application to Samples from a Controlled Study with MDMA

    Microsoft Academic Search

    Frank T. Peters; Nele Samyn; Caroline T. J. Lamers; Wim J. Riedel; Thomas Kraemer; Gert de Boeck; Hans H. Maurer

    Background: The enantiomers of the designer drugs 3,4-methylenedioxyamphetamine (MDA), 3,4-methyl- enedioxymethamphetamine (MDMA), and 3,4-methyl- enedioxyethylamphetamine (MDEA) differ in their pharmacologic and toxicologic potency. The aim of this study was to develop an assay for measuring these enantiomers in small plasma volumes and to analyze samples from a controlled study with MDMA. Methods: The analytes were extracted from <0.2 mL of

  14. Differentiation of the 1-(methylenedioxyphenyl)-2-piperazinopropanes and 1-(methoxyphenyl)-2-piperazinopropanones by GC-IRD and GC-MS.

    PubMed

    Abdel-Hay, Karim M; DeRuiter, Jack; Clark, C Randall

    2014-02-01

    Two amphetamine-like piperazine-containing compounds, 1-(3,4-methylenedioxyphenyl)-2-piperazinopropane (3,4-MDPPP), its positional isomer 1-(2,3-methylenedioxyphenyl)-2-piperazinopropane (2,3-MDPPP) and three methcathinone-like piperazine-containing regioisomeric ring substituted 1-(methoxyphenyl)-2-piperazinopropanones (OMePPPOs) have identical elemental composition and no marked differences in their mass spectra. Perfluoroacylation of the secondary amine nitrogen of these isomeric piperazines gave mass spectra with differences in the relative abundance of some fragment ions but did not alter the fragmentation pathway to provide unique ions for discrimination among these isomers. Gas chromatography coupled to infrared detection (GC-IRD) provides direct confirmatory data for the identification of the carbonyl containing compounds and the differentiation of the 3,4-MDPPP from its direct (2,3-MDPPP) and indirect (OMePPPOs) regioisomers. The vapor phase infrared spectra provide for specific confirmation of each of the isomeric piperazines. The perfluoroacyl derivative forms of the five piperazines involved in this study were resolved on two stationary phases, the first is composed of 100% dimethyl polysiloxane (Rtx-1) and the second of 5% diphenyl and 95% dimethyl polysiloxane (Rtx-5). PMID:24447450

  15. Solubility of carbon dioxide in aqueous solutions of 2-amino-2-methyl-1,3-propanediol

    SciTech Connect

    Baek, J.I.; Yoon, J.H. [Korea Electric Power Research Inst., Taejon (Korea, Republic of). Center for advanced Studies in Energy and the Environment] [Korea Electric Power Research Inst., Taejon (Korea, Republic of). Center for advanced Studies in Energy and the Environment

    1998-07-01

    The equilibrium solubility of carbon dioxide in aqueous solutions of 2-amino-2-methyl-1,3-propanediol (AMPD) has been measured at (30, 40, and 60) C and the partial pressure of carbon dioxide ranging from (0.5 to 3065) kPa. The concentrations of the aqueous solutions were (10 and 30) mass % AMPD. The tendency of the solubility of carbon dioxide in 30 mass % AMPD aqueous solution at 40 C was found to be similar to that in 30 mass % N-methyldiethanolamine aqueous solution.

  16. Effective eradication of pinworms (Syphaciamuris, Syphacia obvelata and Aspiculuris tetraptera) from a rodent breeding colony by oral anthelmintic therapy.

    PubMed

    Zenner, L

    1998-07-01

    An oral combination of piperazine and ivermectin was used over a 6-week period for treating three different colonies of mice or rats infested with Syphacia obvelata, Syphacia muris or Aspiculuris tetraptera. No acute toxic effect was found in transgenic lines of mice or rats with these products in a preliminary trial. The colonies were treated with piperazine, 2.1 mg/ml in tap water for 2 weeks, then with ivermectin, 0.007 mg/ml, in tap water for the third and fourth weeks, and finally with piperazine for two further weeks. Hygiene measures such as a complete cage change, thorough disinfection and cleaning of the rooms were associated with the treatment. All examinations subsequent to completion of treatment have proved negative for further parasites. PMID:9718483

  17. Efficient synthesis of deuterium labeled hydroxyzine and aripiprazole.

    PubMed

    Vohra, Mohit; Sandbhor, Mahendra; Wozniak, Andrew

    2015-06-15

    Hydroxyzine and aripiprazole are active pharmaceutical ingredients that have been largely acknowledged for their antipsychotic properties. Deuterium labeled isotopes of hydroxyzine and aripiprazole are internal standards that can aid in the further research of non-isotopic forms via quantification analysis using HPLC-MS/MS. The synthesis of hydroxyzine-d8 was accomplished by coupling piperazine-d8 with 4-chlorobenzhydryl chloride followed by the reaction of the first intermediate with 2-(2-chloroethoxy) ethanol to afford 11.7% of hydroxyzine-d8 with 99.5% purity. The synthesis of aripiprazole-d8 was also achieved in two steps. 1,4-Dibromobutane-d8 reacted with 7-hydroxy-3,4-dihydro-2(1H)-quinolinone. The first intermediate was then coupled with 1-(2, 3-dichlorophenyl)piperazine hydrochloride to produce 33.4% of aripiprazole-d8 with 99.93% purity. PMID:26011470

  18. Mutagenicity of products generated by the reaction between several antiparasitic drugs and nitrite

    SciTech Connect

    Alba, M.A.; Espinose, J.; Cortinas de Nava, C.

    1988-01-01

    Drugs containing secondary aliphatic amines, heterocyclic nitrogen, or secondary aliphatic amido groups (chloroquine, dehydroemetine, mebendazole, and piperazine) and pyrimidine derivatives such as pyrantel pamoate were reacted in vitro with sodium nitrite at pH 3.7 and became mutagenic for Salmonella typhimurium strain TA1535. The products derived from the nitrosation of chloroquine and dehydroemetine required metabolic activation by mammalian hepatic S9 to be mutagenic. The N-nitroso derivatives of mebendazole, piperazine, and pyrantel pamoate were mutagenic with and without S9, although more activity was noted in the presence of S9 with the nitrosated compounds formed from mebendazole and piperazine. Under identical conditions, no mutagenic products were detected from quaternary ammonium salts such as bephenium hydroxynaphthoate or drugs containing tertiary heterocyclic amino groups, such as iodochlorhydroxyquin.

  19. Synthesis and functional survey of new Tacrine analogs modified with nitroxides or their precursors

    PubMed Central

    Kálai, Tamás; Altman, Robin; Maezawa, Izumi; Balog, Mária; Morisseau, Christophe; Petrlova, Jitka; Hammock, Bruce D.; Jin, Lee-Way; Trudell, James; Voss, John C.; Hideg, Kálmán

    2014-01-01

    A series of new Tacrine analogs modified with nitroxides or pre-nitroxides on 9-amino group via methylene or piperazine spacers were synthesized; the nitroxide or its precursors were incorporated into the Tacrine scaffold. The new compounds were tested for their hydroxyl radical and peroxyl radical scavenging ability, acetyl cholinesterase inhibitor activity and protection against A?-induced cytotoxicity. Based on these assays, we conclude that Tacrine analogs connected to five and six-membered nitroxides via piperazine spacers (9b, 9b/HCl and 12) exhibited the best activity, providing direction for further development of additional candidates with dual functionality (anti Alzheimer’s and antioxidant). PMID:24657571

  20. De novo design of a picomolar nonbasic 5-HT(1B) receptor antagonist.

    PubMed

    Nugiel, David A; Krumrine, Jennifer R; Hill, Daniel C; Damewood, James R; Bernstein, Peter R; Sobotka-Briner, Cynthia D; Liu, Jianwei; Zacco, Anna; Pierson, M Edward

    2010-02-25

    We describe herein the discovery of novel, de novo designed, 5-HT(1B) receptor antagonists that lack a basic moiety and that provide improved hERG and in vitro phospholipidosis profiles. We used a known 5-HT(1B) antagonist template as our starting point and focused on replacing the piperazine moiety. Pyrazole-based ideas were designed and synthesized among a small library of piperazine replacements. To our knowledge, these are the first potent, nonbasic, functionally active antagonists of the 5-HT(1B) receptor. PMID:20088516

  1. Synthesis of chiral 2,3-disubstituted 1,4-diazabicyclo[2.2.2]octane derivatives.

    PubMed

    Periasamy, Mariappan; Edukondalu, Athukuri; Reddy, Polimera Obula

    2015-04-01

    Racemic 2,3-diaryl-1,4-diazabicyclo[2.2.2]octane (DABCO) derivatives are synthesized from the readily accessible piperazines in 50-64% yield by cyclization using ethylene bromide, triethylamine, and KI at 80 °C. The enantiomerically enriched 2,3-diphenylpiperazine and the 2,3-bis(1-naphthyl)piperazine derivatives are prepared by a resolution method using commercially available optically active acids, yielding the corresponding DABCO derivatives in 51-64% yield with up to 99% ee. This mild cyclization can also be applied to enantiopure camphanyldiamine derivatives, and the products are obtained in 72-86% yields. PMID:25756201

  2. CO2 CAPTURE BY ABSORPTION WITH POTASSIUM CARBONATE

    SciTech Connect

    Gary T. Rochelle; A. Frank Seibert; J. Tim Cullinane; Terraun Jones

    2003-01-01

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. Progress has been made in this reporting period on three subtasks. The rigorous Electrolyte Non-Random Two-Liquid (electrolyte-NRTL) model has been regressed to represent CO{sub 2} solubility in potassium carbonate/bicarbonate solutions. An analytical method for piperazine has been developed using a gas chromatograph. Funding has been obtained and equipment has been donated to provide for modifications of the existing pilot plant system with stainless steel materials.

  3. Pharmacomodulation on the 3-acetylursolic acid skeleton: Design, synthesis, and biological evaluation of novel N-{3-[4-(3-aminopropyl)piperazinyl]propyl}-3-O-acetylursolamide derivatives as antimalarial agents.

    PubMed

    Gnoatto, Simone C B; Susplugas, Sophie; Dalla Vechia, Luciana; Ferreira, Thais B; Dassonville-Klimpt, Alexandra; Zimmer, Karine R; Demailly, Catherine; Da Nascimento, Sophie; Guillon, Jean; Grellier, Philippe; Verli, Hugo; Gosmann, Grace; Sonnet, Pascal

    2008-01-15

    A series of new piperazine derivatives of ursolic acid was synthesized and tested against Plasmodium falciparum strains. They were also tested on their cytotoxicity effects upon MRC-5 cells. Seven new piperazinyl analogues showed significant activity in the nanomolar range (IC(50)=78-167nM) against Plasmodium falciparum CQ-resistant strain FcB1. A possible mechanism of interaction implicating binding of these compounds to beta-hematin was supported by in vitro tests. Moreover, the importance of the hydrophilic framework attached at the terminal nitrogen atom of the bis-(3-aminopropyl)piperazine joined to the triterpene ring was also explored through molecular dynamic simulations. PMID:17967541

  4. Synthesis and functional survey of new Tacrine analogs modified with nitroxides or their precursors.

    PubMed

    Kálai, Tamás; Altman, Robin; Maezawa, Izumi; Balog, Mária; Morisseau, Christophe; Petrlova, Jitka; Hammock, Bruce D; Jin, Lee-Way; Trudell, James R; Voss, John C; Hideg, Kálmán

    2014-04-22

    A series of new Tacrine analogs modified with nitroxides or pre-nitroxides on 9-amino group via methylene or piperazine spacers were synthesized; the nitroxide or its precursors were incorporated into the Tacrine scaffold. The new compounds were tested for their hydroxyl radical and peroxyl radical scavenging ability, acetylcholinesterase inhibitor activity and protection against A?-induced cytotoxicity. Based on these assays, we conclude that Tacrine analogs connected to five and six-membered nitroxides via piperazine spacers (9b, 9b/HCl and 12) exhibited the best activity, providing direction for further development of additional candidates with dual functionality (anti Alzheimer's and antioxidant). PMID:24657571

  5. Ascorbate-Nitrite Reaction: Possible Means of Blocking the Formation of Carcinogenic N-Nitroso Compounds

    Microsoft Academic Search

    Sidney S. Mirvish; Lawrence Wallcave; Michael Eagen; Philippe Shubik

    1972-01-01

    The formation of carcinogenic N-nitroso compounds by the chemical reaction between nitrous acid and oxytetracycline, morpholine, piperazine, N-methylaniline, methylurea, and (in some experiments) dimethylamine was blocked by ascorbic acid. The extent of blocking depended on the compound nitrosated and on the experimental conditions. Urea and ammonium sulfamate were less effective as blocking agents. The possibility of in vivo formation of

  6. Studies of flammability and thermal degradation for flame retardant cotton fabric with P-N containing derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effectiveness of a phosphoramidate Tetraethyl piperazine-1,4- diyldiphosphoramidate (TEPP) as a flame retardant (FR) on cotton twill fabrics was compared with that of a previously studied Diethyl 4- methylpiperazin-1-ylphosphoramidate (DEPP). TEPP was formed in a reaction between two phosphonat...

  7. Adsorption and desorption of atrazine on a melamine-based soil amendment 

    E-print Network

    Neitsch, Susan Lynn

    2004-09-30

    Adsorption kinetics and adsorption-desorption of atrazine on organoclay composites prepared with the surfactant 6-piperazin-1-yl-N,N'-bis-(1,1,3,3-tetramethyl-butyl)-(1,3,5)triazine-2,4-diamine and Houston Black clay were ...

  8. Adsorption and desorption of atrazine on a melamine-based soil amendment

    E-print Network

    Neitsch, Susan Lynn

    2004-09-30

    Adsorption kinetics and adsorption-desorption of atrazine on organoclay composites prepared with the surfactant 6-piperazin-1-yl-N,N'-bis-(1,1,3,3-tetramethyl-butyl)-(1,3,5)triazine-2,4-diamine and Houston Black clay were studied using the indirect...

  9. Use of anthelmintics in herbivores and evaluationof risks for the non target fauna of pastures

    Microsoft Academic Search

    Jean-Pierre Lumaret; Faiek Errouissi

    2002-01-01

    The overall purpose of this paper was to review the major and most recent literature relat- ing the effects of anthelmintics on dung breeding invertebrates and dung degradation. Faecal residues or metabolites of drugs belonging to the benzimidazole and levamisole\\/morantel groups are relatively harmless to dung fauna, on the contrary to other anthelmintics such as coumaphos, dichlorvos, pheno- thiazine, piperazine,

  10. ORIGINAL PAPER Synthesis and Crystal Structures of N,N0

    E-print Network

    Pike, Robert D.

    that exhibit favorable pharmacological properties. Piperazine is conveniently substituted at the N and N0 to engage in bridging behavior between metal centers despite the well- known thermodynamic preference with the intention of producing photolumi- nescent network complexes with copper(I) salts. Cop- per(I) halide

  11. Effects of the electrode size and modification protocol on a label-free electrochemical biosensor.

    PubMed

    Arya, Sunil K; Pui, Tze Sian; Wong, Chee Chung; Kumar, Sai; Rahman, Abdur Rub Abdur

    2013-06-01

    In the present work, the effect of a surface modification protocol along with the electrode size has been investigated for developing an efficient, label-free electrochemical biosensing method for diagnosis of traumatic brain injury (TBI) biomarkers. A microdisk electrode array (MDEA) and a macroelectrode with a comb structure (MECS) were modified with an anti-GFAP (GFAP = glial fibrillary acidic protein) antibody using two protocols for optimum and label-free detection of GFAP, a promising acute-phase TBI biomarker. For the MDEA, an array of six microdisks with a 100 ?m diameter and, for the MECS, a 3.2 mm × 5.5 mm electrode 5 ?m wide with 10 ?m spaced comb fingers were modified using an optimized protocol for dithiobis(succinimidyl propionate) (DSP) self-assembled monolayer formation. Anti-GFAP was covalently bound, and the remaining free DSP groups were blocked using ethanolamine (Ea). Sensors were exposed to solutions with different GFAP concentrations, and a label-free electrochemical impedance spectroscopy (EIS) technique was used to determine the concentration. EIS results confirmed that both types of Ea/anti-GFAP/DSP/Au electrodes modified with an optimized DSP-based protocol can accurately detect GFAP in the range of 1 pg mL(-1) to 100 ng mL(-1) with a detection limit of 1 pg mL(-1). However, the cross-use of the MDEA protocol on the MECS and vice versa resulted in very low sensitivity or poor signal resolution, underscoring the importance of proper matching of the electrode size and type and the surface modification protocol. PMID:23651210

  12. Intoxikation mit Amphetaminen und Designer-Drogen

    Microsoft Academic Search

    N. Felgenhauer; T. Zilker

    1999-01-01

    Zum Thema  \\u000a Amphetamin und seine Derivate gehören zu den Psychostimulantien. Auf der Basis der chemischen Struktur (seitenketten- oder\\u000a ringsubstituierte Amphetamine) werden Weckamine, Appetitzügler und Halluzinogene unterschieden. Eine besondere Rolle spielen\\u000a die beiden Designerdrogen Methylendioximethamphetamin (MDMA, Straßenname: Ecstasy) und Methylendioxiethamphetamin (MDEA, Straßenname:\\u000a Eve).\\u000a \\u000a \\u000a \\u000a Sie bewirken beim Abhängigen ein Gefühl der Nähe zu anderen Menschen, Angstfreiheit im sozialen Kontakt, eine Intensivierung\\u000a akustischer

  13. Endogenous generation of hydrogen sulfide and its regulation in Shewanella oneidensis

    PubMed Central

    Wu, Genfu; Li, Ning; Mao, Yinting; Zhou, Guangqi; Gao, Haichun

    2015-01-01

    Hydrogen sulfide (H2S) has been recognized as a physiological mediator with a variety of functions across all domains of life. In this study, mechanisms of endogenous H2S generation in Shewanella oneidensis were investigated. As a research model with highly diverse anaerobic respiratory pathways, the microorganism is able to produce H2S by respiring on a variety of sulfur-containing compounds with SirACD and PsrABC enzymatic complexes, as well as through cysteine degradation with three enzymes, MdeA, SO_1095, and SseA. We showed that the SirACD and PsrABC complexes, which are predominantly, if not exclusively, responsible for H2S generation via respiration of sulfur species, do not interplay with each other. Strikingly, a screen for regulators controlling endogenous H2S generation by transposon mutagenesis identified global regulator Crp to be essential to all H2S-generating processes. In contrast, Fnr and Arc, two other global regulators that have a role in respiration, are dispensable in regulating H2S generation via respiration of sulfur species. Interestingly, Arc is involved in the H2S generation through cysteine degradation by repressing expression of the mdeA gene. We further showed that expression of the sirA and psrABC operons is subjected to direct regulation of Crp, but the mechanisms underlying the requirement of Crp for H2S generation through cysteine degradation remain elusive. PMID:25972854

  14. Endogenous generation of hydrogen sulfide and its regulation in Shewanella oneidensis.

    PubMed

    Wu, Genfu; Li, Ning; Mao, Yinting; Zhou, Guangqi; Gao, Haichun

    2015-01-01

    Hydrogen sulfide (H2S) has been recognized as a physiological mediator with a variety of functions across all domains of life. In this study, mechanisms of endogenous H2S generation in Shewanella oneidensis were investigated. As a research model with highly diverse anaerobic respiratory pathways, the microorganism is able to produce H2S by respiring on a variety of sulfur-containing compounds with SirACD and PsrABC enzymatic complexes, as well as through cysteine degradation with three enzymes, MdeA, SO_1095, and SseA. We showed that the SirACD and PsrABC complexes, which are predominantly, if not exclusively, responsible for H2S generation via respiration of sulfur species, do not interplay with each other. Strikingly, a screen for regulators controlling endogenous H2S generation by transposon mutagenesis identified global regulator Crp to be essential to all H2S-generating processes. In contrast, Fnr and Arc, two other global regulators that have a role in respiration, are dispensable in regulating H2S generation via respiration of sulfur species. Interestingly, Arc is involved in the H2S generation through cysteine degradation by repressing expression of the mdeA gene. We further showed that expression of the sirA and psrABC operons is subjected to direct regulation of Crp, but the mechanisms underlying the requirement of Crp for H2S generation through cysteine degradation remain elusive. PMID:25972854

  15. Formulated solvents: New opportunities for energy efficient separation of acid gases

    SciTech Connect

    Chakma, A. [Univ. of Calgary, Alberta (Canada). Dept. of Chemical and Petroleum Engineering] [Univ. of Calgary, Alberta (Canada). Dept. of Chemical and Petroleum Engineering

    1999-01-01

    A formulated amine can be broadly defined as an amine that has been specifically formulated to perform specific task, for example, selective separation of H{sub 2}S from light hydrocarbons in the presence of CO{sub 2}, bulk separation of CO{sub 2}, and so on. A formulated amine can consist of a single solvent such as methyl diethanolamine (MDEA) or a solvent mixture such as a mixture of MDEA and diethanolamine (DEA) in aqueous solutions. Most of the proprietary solvents marketed by the major solvent manufacturers are based on formulated amines. By judicious choice of a formulated amine or amine mixture, process efficiency of the existing plants can be enhanced significantly compared to the use of traditional amines. Furthermore, some of the gas processing problems that can not be dealt with using the conventional technology in an economical manner can be easily handled with formulated amines. EOR gas processing is such an example. In the case of EOR gas processing, the concentration and volume of CO{sub 2} to be separated from the produced gas increases with time. This creates a major challenge for the design engineer in the design of a processing plant flexible enough to handle variations in CO{sub 2} concentrations ranging from 0 to 80%. Formulated amines may be an answer to this problem. This article will describe the challenges and the opportunities formulated amines may provide to the gas processing industry.

  16. Treat LPGs with amines

    SciTech Connect

    Nielsen, R.B. [Fluor Daniel, Inc., Irvine, CA (United States); Rogers, J. [Koch Engineering, Inc., Wichita, KS (United States); Bullin, J.A.; Duewall, K.J. [Bryan Research and Engineering, Inc., Bryan, TX (United States)

    1997-09-01

    In recent years, there has been increasing interest in sweetening liquefied petroleum gases (LPGs) with amines. However, limited data and design information are available in the literature. This article reviews the fundamental aspects of LPG amine treaters and includes guidelines, design considerations and alternatives for static mixers, jet eductor mixers and columns with structured packing, random packing and sieve trays. All of these current design methods are compared based on plant operating data. Guidelines are given for sweetening LPGs with amines including amine type, concentration, filtration, temperature, loading, circulation rate and water-wash systems. Also covered is the contacting method used in the absorber. Any of the commonly available amines such as monoethanolamine (MEA), diethanolamine (DEA), diglycolamine (DGA), methyl diethanolamine (MDEA) and MDEA-based solvents usually perform satisfactorily. Design criteria for distributors and LPG disperser plates, amine filtration and LPG settlers and coalescers are important. The contacting method is also important and includes jet eductor mixers, static mixers, and columns with sieve trays, random packing and structured packing.

  17. Simultaneous removal of water and BTEX from feed gas for a cryogenic plant

    SciTech Connect

    Jones, S.; Lee, S.; Evans, M.; Chen, R.

    1999-07-01

    The removal of water and benzene, toluene, ethyl benzene, xylene (BTEX) from the feed gas of a cryogenic plant is critical in order to avoid precipitation of these components in the cold section of the plant. The design of the Hannibal Gas Plant in Sfax, Tunisia, accomplishes the removal of water and BTEX simultaneously. The plant receives 7.1 million Nm{sub 3}/day of feed gas and produces high heating value pipeline quality sales gas by removing nitrogen in the cold box. A methyl diethanol amine (MDEA) treating system at the front end of the plant is designed to remove carbon dioxide. The glycol system takes the saturated gas from the MDEA contactor and reduces the water content to 7 lb/MMscf. The glycol system is also designed to remove more than half of the BTEX from the feed gas so that these aromatic components will not precipitate in the cold section of the plant. GPA experimental data were used to fit the interaction parameters for the computer simulator used to design the glycol system. The results of the plant performance test verify the validity of the design.

  18. Analysis of underivatized amphetamines and related phenethylamines with high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.

    PubMed

    Bogusz, M J; Krüger, K D; Maier, R D

    2000-03-01

    Amphetamine, methamphetamine, illicit designer phenethylamines (MDA, MDEA, MDMA, MBDB, and BDMPEA), and other phenethylamines (benzyl-1-phenylethylamine, cathinone, ephedrine, fenfluramine, norfenfluramine, phentermine, 1-phenylethylamine, phenylpropanolamine, and propylhexedrine) were extracted from serum using a solid-phase extraction procedure. The extracts were examined with high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS). The drugs were separated on ODS column in acetonitrile/50 mM ammonium formate buffer (pH 3.0) (25:75) as a mobile phase. Full-scan mass spectra of drugs examined by means of APCI with collision-induced dissociation showed protonated molecular ions and fragments typical for particular drugs. LC-APCI-MS allowed an unequivocal differentiation of all drugs involved. The quantitation was performed using selected ion monitoring of protonated molecular ions and fragments of drugs involved and their deuterated analogues. The limits of detection ranged from 1 to 5 microg/L serum, and the recoveries ranged from 58 to 96%. A linear response was observed for all drugs in the range from 5 to 500 microg/L. The method was applied for routine determination of amphetamine, MDMA, MDA, and MDEA in one run. Solid-phase extraction used assured simultaneous isolation of various groups of basic drugs of forensic interest (opiates, cocaines, phenethylamines, and benzodiazepines) from biofluids. PMID:10732943

  19. Correlation and prediction of the solubility of carbon dioxide in a mixed alkanolamine solution

    SciTech Connect

    Li, Y.G.; Mather, A.E. (Univ. of Alberta, Edmonton (Canada). Dept. of Chemical Engineering)

    1994-08-01

    Aqueous alkanolamine solutions are frequently used for the removal of acidic gases, such as CO[sub 2] and H[sub 2]S from industrial and natural gases. The Clegg-Pitzer equations, expressed on a mole fraction basis, comprise an extended Debye-Hueckel term which is a function of composition and a Margules expansion carried out to the three-suffix level, with some simplifications are used to correlate and predict the vapor-liquid equilibrium data for the CO[sub 2]-mixed amine aqueous system. The interaction parameters determined from data for the binary and ternary (single amine) systems can be used to predict the quaternary mixed amine system without any additional parameters. The model is applied to the CO[sub 2]-MDEA-MEA-H[sub 2]O system containing three neutral solvents (MDEA, MEA, and H[sub 2]O) and four ionic species (MDEAH[sup +], MEAH[sup +], HCO[sub 3][sup [minus

  20. Characterization of electroconductive blends of poly(HEMA-co-PEGMA-co-HMMA-co-SPMA) and poly(Py-co-PyBA).

    PubMed

    Justin, Gusphyl; Guiseppi-Elie, Anthony

    2009-09-14

    Electroconductive hydrogels (ECH) prepared as blends of UV-cross-linked poly(hydroxyethylmethacrylate) [p(HEMA)]-based hydrogels and electropolymerized polypyrrole (PPy) were synthesized as coatings on microlithographically fabricated interdigitated microsensor electrodes (IMEs) and microdisc electrode arrays (MDEAs). Hydrogels were synthesized from tetraethyleneglycol diacrylate (TEGDA), hydroxyethylmethacrylate (HEMA), polyethyleneglycol monomethacrylate (PEGMA), N-[tris(hydroxymethyl)methyl]-acrylamide (HMMA), and 3-sulfopropyl methacrylate potassium salt (SPMA) to produce p(HEMA-co-PEGMA-co-HMMA-co-SPMA) hydrogels. The conductive polymer was synthesized from pyrrole and 4-(3'-pyrrolyl)butyric acid by electropolymerization within the electrode-supported hydrogel. ECH films produced with different electropolymerization charge densities were investigated using cyclic voltammetry, electrical impedance spectroscopy, differential scanning calorimetry (DSC), and thermal gravimetric analysis (TGA). Polymer morphology was studied by SEM. The ECH demonstrated the desired characteristics of high electrical conductivity (low impedance), as well as high thermal stability compared to pure hydrogel. Signal enhancement was achieved by modifying the surface of an MDEA biotransducer with the ECH, with a 10-fold increase in the voltammetric current response associated with the ferrocene monocarboxylic acid (FcCO(2)H) redox reaction. PMID:19705837

  1. Experimental equilibrium between acid gases and ethanolamine solutions

    SciTech Connect

    Bhairi, A.M.

    1984-01-01

    The general subject area of this study is equilibrium solubility of carbon dioxide and hydrogen sulfide in solutions of some common ethanolamines. The amines studied are most widely used in the area of gas sweetening. They include monoethanolamine, diglycolamine, diethanolamine and methyldiethanolamine. Only limited data are available for some of these amines. The process involved developing simple apparatus and procedure for investigating the equilibrium solubility of carbon dioxide and hydrogen sulfide in aqueous alkanolamine solutions. The procedure uses a single equilibrium cell. No gas chromatograph nor liquid chemical analysis is required. Measurements of the solubility were made in different amine solution concentrations at acid gas partial pressures to 1000 psia and temperatures from 77 to 240{degree}F. The method used was found to be sound as indicated by the consistency and reproducibility of the data.

  2. Heterometallic 3d-4f single-molecule magnets: ligand and metal ion influences on the magnetic relaxation.

    PubMed

    Langley, Stuart K; Le, Crystal; Ungur, Liviu; Moubaraki, Boujemaa; Abrahams, Brendan F; Chibotaru, Liviu F; Murray, Keith S

    2015-04-01

    Six tetranuclear 3d–4f single-molecule magnet (SMM) complexes formed using N-n-butyldiethanolamine and N-methyldiethanolamine in conjunction with ortho- and para-substituted benzoic acid and hexafluoroacetoacetone ligands yield two families, both having a butterfly metallic core. The first consists of four complexes of type {Co2(III)Dy2(III)} and {Co2(III)Co(II)Dy(III)} using N-n-butyldiethanolamine with variation of the carboxylate ligand. The anisotropy barriers are 80 cm–1, (77 and 96 cm–1—two relaxation processes occur), 117 and 88 cm–1, respectively, each following a relaxation mechanism from a single DyIII ion. The second family consists of a {Co2(III)Dy2(III)} and a {Cr2(III)Dy2(III)} complex, from the ligand combination of N-methyldiethanolamine and hexafluoroacetylacetone. Both show SMM behavior, the Co(III) example displaying an anisotropy barrier of 23 cm–1. The Cr(III) complex displays a barrier of 28 cm–1, with longer relaxation times and open hysteresis loops, the latter of which is not seen in the Co(III) case. This is a consequence of strong Dy(III)–Cr(III) magnetic interactions, with the relaxation arising from the electronic structure of the whole complex and not from a single DyIII ion. The results suggest that the presence of strong exchange interactions lead to significantly longer relaxation times than in isostructural complexes where the exchange is weak. The study also suggests that electron-withdrawing groups on both bridging (carboxylate) and terminal (?-diketonate) ligands enhance the anisotropy barrier. PMID:25796958

  3. Vibrational spectrum of buspirone

    NASA Astrophysics Data System (ADS)

    Cybulski, Jacek; Chilmonczyk, Zdzis?aw; Glice, Magdalena; Cybulski, Marcin; Bajdor, Krzysztof; Le?, Andrzej

    1997-02-01

    The IR and Raman spectra of buspirone and buspirone hydrochloride were recorded in KBr pellets and chloroform solutions. Most of the vibrational bands were assigned to normal modes using quantum mechanical semiempirical and ab initio restricted Hartree-Fock (RHF) calculations on model systems. The essential spectral characteristics can be obtained from the analysis of three building blocks of buspirone, i.e. pyrimidine-piperazine, butyl spacer and imide residues. The spectral regions particularly sensitive to intermolecular interactions were identified. The theoretical calculations suggest that the "NH +" band in buspirone hydrochloride reflects the formation of a moderately strong hydrogen bond between the protonated piperazine nitrogen atom (bound to the butyl spacer) and the chlorine anion.

  4. trans-1-[(2-Phenylcyclopropyl)methyl]-4-arylpiperazines: mixed dopamine D(2)/D(4) receptor antagonists as potential antipsychotic agents.

    PubMed

    Zhang, X; Hodgetts, K; Rachwal, S; Zhao, H; Wasley, J W; Craven, K; Brodbeck, R; Kieltyka, A; Hoffman, D; Bacolod, M D; Girard, B; Tran, J; Thurkauf, A

    2000-10-19

    The dopaminergic receptor profile of a series of trans-1-[(2-phenylcyclopropyl)methyl]-4-arylpiperazines was examined. Aromatic substitution patterns were varied with the goal of identifying a compound having affinities for the D(2) and D(4) receptors in a ratio similar to that observed for the atypical neuroleptic clozapine. The compounds (1S, 2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2, 4-dichlorophenyl)piperazine (5m) and (1S, 2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2, 4-dimethylphenyl)piperazine (5t) were selected for functional antagonists at D(2) and D(4) receptors and had a D(2)/D(4) ratio approximating that of clozapine; they proved inactive in behavioral tests of antipsychotic activity. PMID:11052797

  5. 'Catalysts' for polyacrylamide gel polymerization and detection of proteins by silver staining.

    PubMed

    Hochstrasser, D F; Merril, C R

    1988-01-01

    The crosslinker diacrylyl-piperazine produces polyacrylamide gels which display improved electrophoretic separation of proteins and better physical strength. It also produces gels with improved detection of proteins by ammoniacal silver staining by reducing the background. This reduced background provided us with an opportunity to investigate residual background staining caused by the catalytic reagents utilized in the polymerization of acrylamide gels. The commonly used catalyst system, tetramethyl-ethylenediamine and ammonium persulfate was shown to be responsible for the yellow staining background found after a prolonged development time with silver staining. An alternate catalyst system has been designed to decrease further the formation of this background staining. Dimethyl-piperazine or tetramethylethylenediamine, potassium or ammonium persulfate, and sodium thiosulfate are shown to provide for gels which have excellent mechanical and staining characteristics. These catalytic systems produce little background staining despite prolonged development time with the ammoniacal silver stain, and they reduce background staining with the dichromate silver stain. PMID:2484987

  6. CO{sub 2} CAPTURE BY ABSORPTION WITH POTASSIUM CARBONATE

    SciTech Connect

    Gary T. Rochelle; J.Tim Cullinane; Marcus Hilliard; Eric Chen; Babatunde Oyenekan; Ross Dugas

    2005-01-31

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. Thermodynamic modeling predicts that the heat of desorption of CO{sub 2} from 5m K+/2.5 PZ from 85 kJ/mole at 40 C to 30 kJ/mole at 120 C. Mass transfer modeling of this solvent suggests that carbonate and general salt concentration play a major role in catalyzing the rate of reaction of CO{sub 2} with piperazine. Stripper modeling suggests that with the multipressure stripper, the energy consumption with a generic solvent decreases by 15% as the heat of desorption is decreased from 23.8 to 18.5 kcal/gmol. A second pilot plant campaign with 5m K+/2.5 PZ was successfully completed.

  7. Active drug metabolites. An overview of their relevance in clinical pharmacokinetics.

    PubMed

    Garattini, S

    1985-01-01

    This review underlines the importance of considering in the overall evaluation of drug effect and efficacy not only the kinetics and activities of the administered drug, but also those of the chemical species (metabolites) which are formed in the body. The circumstances in which a role for active drug metabolites may be suspected are described, and a number of specific examples are given. Four different categories are described: drugs which are inactive precursors of active metabolites (e.g. DOPA and cyclophosphamide); active metabolites which contribute to the duration of action of the parent compound (e.g. hexamethylmelamine and clobazam); active metabolites showing a mechanism of action different from that of the parent compound (e.g. buspirone and 1-pyrimidinyl piperazine; fenfluramine and norfenfluramine); and active metabolites showing an antagonistic effect on the activity of the parent drug (e.g. trazodone and m-chlorophenyl-piperazine; aspirin and salicylate). PMID:2861928

  8. CO2 Capture by Absorption with Potassium Carbonate

    SciTech Connect

    Gary T. Rochelle; Eric Chen; Babatunde Oyenekan; Andrew Sexton; Amorvadee Veawab

    2006-04-28

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. The final campaign of the pilot plant was completed in February 2006 with 5m K{sup +}/2.5m PZ and 6.4m K{sup +}/1.6m PZ using Flexipac AQ Style 20. The new cross-exchanger reduced the approach temperature to less than 9 C. Stripper modeling has demonstrated that a configuration with a ''Flashing Feed'' requires 6% less work that a simple stripper. The oxidative degradation of piperazine proceeds more slowly than that of monoethanolamine and produces ethylenediamine and other products. Uninhibited 5 m KHCO{sub 3}/2.5 m PZ corrodes 5 to 6 times faster that 30% MEA with 0.2 mol CO{sub 2}/mol MEA.

  9. CO2 Capture by Absorption with Potassium Carbonate

    SciTech Connect

    Gary T. Rochelle; Eric Chen; Babatunde Oyenekan; Andrew Sexton; Jason Davis; Marcus Hilliard; Amorvadee Veawab

    2006-07-28

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. The pilot plant data have been reconciled using 17% inlet CO{sub 2}. A rate-based model demonstrates that the stripper is primarily controlled by liquid film mast transfer resistance, with kinetics at vacuum and diffusion of reactants and products at normal pressure. An additional major unknown ion, probably glyoxylate, has been observed in MEA degradation. Precipitation of gypsum may be a feasible approach to removing sulphate from amine solutions and providing for simultaneous removal of CO{sub 2} and SO{sub 2}. Corrosion of carbon steel in uninhibited MEA solution is increased by increased amine concentration, by addition of piperazine, and by greater CO{sub 2} loading.

  10. CO2 CAPTURE BY ABSORPTION WITH POTASSIUM CARBONATE

    SciTech Connect

    Gary T. Rochelle; Eric Chen; J.Tim Cullinane; Marcus Hilliard; Jennifer Lu; Babatunde Oyenekan; Ross Dugas

    2004-07-29

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. CO{sub 2} mass transfer rates are second order in piperazine concentration and increase with ionic strength. Modeling of stripper performance suggests that 5 m K{sup +}/2.5 m PZ will require 25 to 46% less heat than 7 m MEA. The first pilot plant campaign was completed on June 24. The CO{sub 2} penetration through the absorber with 20 feet of Flexipac{trademark} 1Y varied from 0.6 to 16% as the inlet CO{sub 2} varied from 3 to 12% CO{sub 2} and the gas rate varied from 0.5 to 3 kg/m{sup 2}-s.

  11. Thermochemistry of adducts of cobalt(II) acetylacetonate chelate with heterocyclic bases

    Microsoft Academic Search

    P. O. Dunstan

    1997-01-01

    The compounds Co(AcAc)2·nL, where AcAc represents acetylacetonate, L the piperazine (Pipz), morpholine (Morph), piperidine (Pipd), pyridine (Py), 3-methylpyridine (?-Pico), 4-methylpyridine (?-Pico), 3-cyanopyridine (3-cyanopy), 4-cyanopyridine (4-cyanopy), 2,2?-bipyridine (Bipy) or quinoline (Quin); n = 1 or 2) were synthesized and characterized by melting points, elemental analysis, thermal studies and electronic and IR spectroscopy. The enthalpies of dissolution in 10% (v\\/v) ethanolamine in

  12. Novel Approach for Comparing the Abilities of Quinolones To Restrict the Emergence of Resistant Mutants during Quinolone Exposure?

    PubMed Central

    Malik, Muhammad; Hoatam, Gerard; Chavda, Kalyan; Kerns, Robert J.; Drlica, Karl

    2010-01-01

    An agar-plate assay was adapted to examine aspects of quinolone structure that restrict the emergence of quinolone-mediated quinolone resistance. When Escherichia coli was applied to agar containing nalidixic acid, the number of quinolone-resistant mutants arising during incubation was decreased by raising the drug concentration and by mutations expected to block the induction of the SOS response (recA, lexA); the mutant number was increased by a mutator mutation (ung). The examination of four related fluoroquinolones then revealed that a C-8 methoxy group and an N-ethyl piperazine substituent at C-7 reduced mutant acquisition more effectively than C-8 H and C-7 C-ethyl piperazine groups. The fluoroquinolone that was most effective at restricting mutant acquisition was the most active when lethal activity was measured on agar plates or in liquid medium (as minimal bactericidal concentration). It also exhibited the lowest ratio of mutant MIC to wild-type MIC when it was tested with a set of isogenic gyrase mutants, and it had a low mutant prevention concentration (MPC) relative to MIC. However, a low MPC was less likely to be important in restricting the induced mutant accumulation because a fluoroquinolone N-ethyl piperazine substituent was more effective than a C-ethyl piperazine substituent at reducing mutant accumulation but was less effective at lowering the MPC. An 8-methoxy-quinazoline-2,4-dione was also effective at restricting the accumulation of resistant mutants on agar. Collectively, these data characterize a simple assay for detection of drug-mediated resistance that is sensitive to the structures of GyrA inhibitors. The assay provides a new method for screening quinolones and quinolone-like molecules that complements MPC-based tests for restricting the emergence of resistance. PMID:19805561

  13. Singular value decomposition analysis of the torsional angles of dopamine reuptake inhibitor GBR 12909 analogs: effect of force field and charges

    Microsoft Academic Search

    Deepangi Pandit; Anna Fiorentino; Supreet Bindra; Carol A. Venanzi

    2011-01-01

    Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis of large, flexible molecules, such as the\\u000a dopamine reuptake inhibitor GBR 12909 (1), is complicated by the fact that they can take on a wide range of closely-related conformations. The first step in the analysis\\u000a is to classify the conformers into groups. Over 600 conformers each of a piperazine (2) and piperidine (3) analog

  14. A near-infrared fluorescence turn-on sensor for sulfide anions.

    PubMed

    Cao, Xiaowei; Lin, Weiying; He, Longwei

    2011-09-01

    The first NIR fluorescent sensor for sulfide anions was constructed based on the displacement approach. The sensing ensemble is composed of a cyanine dye, a piperazine linker, an 8-aminoquinoline ligand, and copper. The favorable attributes of the sensor include a large NIR fluorescence turn-on signal in aqueous ethanol, high sensitivity, and high selectivity. The transition-metal-based displacement strategy may open an avenue for development of NIR fluorescent sensors for a wide variety of anion targets. PMID:21809838

  15. The Selective 5HT6 Receptor Antagonist Ro4368554 Restores Memory Performance in Cholinergic and Serotonergic Models of Memory Deficiency in the Rat

    Microsoft Academic Search

    Cindy K J Lieben; Arjan Blokland; Ayhan ??k; Eric Sung; Petra van Nieuwenhuizen; Rudy Schreiber; CKJ Lieben

    2005-01-01

    Antagonists at serotonin type 6 (5-HT6) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT6 antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and

  16. Investigation of the Inaccuracy of NIOSH Method 5505 for Estimating the Concentration of Isocyanate in Air

    Microsoft Academic Search

    Martha J. Seymour; Paula Fey OConnor; Alexander W. Teass

    1990-01-01

    NIOSH Method 5505 for estimating isocyanate in workplace air is based on sampling air with an impinger containing a standard solution of 1-(2-methoxyphenyl)piperazine in toluene and relating the measured loss of reagent from the sample to the total quantity of isocyanate trapped from the air. An experiment, in which 0–740 L of isocyanate-free air was sampled at 0.4–1.6 L\\/min and

  17. Process for the reduction of nitrogen oxides in an effluent

    SciTech Connect

    Epperly, W.R.; Sullivan, J.C.; Sprague, B.N.

    1989-09-05

    This patent describes a process for the reduction of the concentration of nitrogen oxides in the effluent from the combustion of a carbonaceous fuel. The process comprises introducing a heterocyclic hydrocarbon selected from the group consisting of piperazine, piperidine, pyrazine, pyrazole, imidazole, oxazolidone, pyrrole and pyrrolidine into the effluent having an effluent temperature of greater than about 1200{sup 0}F. under conditions effective to reduce the concentration of nitrogen oxides in the effluent.

  18. On the nature of boron-carbon-nitrogen compounds synthesised from organic precursors

    Microsoft Academic Search

    Yuri G. Andreev; Torsten Lundström; Robin K. Harris; Se-Woung Oh; David C. Apperley; Derek P. Thompson

    1995-01-01

    Three compounds were prepared through pyrolysis of organic precursors, namely pyridine-borane, piperazine-borane, poly(acrylonitrile)-BCl3, following the routes proposed in the literature for the synthesis of single-phase boron carbonitrides of various compositions. X-ray diffraction and MAS NMR studies performed on the powders obtained suggest that the resulting compounds are mixtures of amorphous boron and turbostratically distorted hexagonal boron nitride and graphite rather

  19. Rhenium and technetium tricarbonyl complexes anchored by 5HT 1A receptor-binding ligands containing P,O\\/N donor atom sets

    Microsoft Academic Search

    Elisa Palma; João D. G. Correia; Ângela Domingos; Isabel Santos; Roger Alberto; Hartmut Spies

    2004-01-01

    The (2-methoxyphenyl)piperazine pharmacophore, a part of the WAY 100635 structure, has been functionalized with phosphinoarylbenzylamide or phosphinoarylbenzylamine chelator groups using propylene or hexylene alkyl chains as linkers (L2–L4). These heterofunctionalized phosphines bearing an arylpiperazine moiety have been used to stabilize rhenium tricarbonyl complexes of the type [Re(CO)3Br(?2-L)] (4, L=L2; 5, L=L3; 6, L=L4), which have been fully characterized, including by

  20. Contrasting Roles of the N-Methyl-d-Aspartate Receptor in the Production of Immobilization by Conventional and Aromatic Anesthetics

    Microsoft Academic Search

    Edmond I Eger; Mark Liao; Michael J. Laster; Albert Won; John Popovich; Douglas E. Raines; Ken Solt; Robert C. Dutton; Franklin V. Cobos; James M. Sonner

    2006-01-01

    We hypothesized that N-methyl-d-aspartate (NMDA) receptors mediate some or all of the capacity of inhaled anesthetics to prevent movement in the face of noxious stimulation, and that this capacity to prevent move- ment correlates directly with the in vitro capacity of such anesthetics to block the NMDA receptor. To test thishypothesis,wemeasuredtheeffectofIVinfusionof the NMDA blockers dizocilpine (MK-801) and (R)-4-(3- phosphonopropyl) piperazine-2-carboxylic

  1. Convenient Synthesis of Novel 2-Substituted Imidazopyrazinone Derivatives

    Microsoft Academic Search

    Yanyun Zhu; Gonghua Song; Peng Lu; Mingjie Zhu; Yilang Chen

    2011-01-01

    Starting from commercially available piperazine-2-carboxylic acid, a series of novel 2-aryl and 2-benzyl substituted imidazopyrazinone were prepared. The intermediates 5a–g were obtained through facile Buchwald–Hartwig coupling reaction, the effects of catalyst, base and solvent on the coupling reaction were investigated. The optimal reaction conditions for the coupling reaction were PdCl2(dppf)\\/NaO-t-Bu\\/toluene.

  2. Convenient Synthesis of Novel 2-Substituted Imidazopyrazinone Derivatives

    Microsoft Academic Search

    Yanyun Zhu; Gonghua Song; Peng Lu; Mingjie Zhu; Yilang Chen

    2012-01-01

    Starting from commercially available piperazine-2-carboxylic acid, a series of novel 2-aryl and 2-benzyl substituted imidazopyrazinone were prepared. The intermediates 5a–g were obtained through facile Buchwald–Hartwig coupling reaction, and the effects of catalyst, base, and solvent on the coupling reaction were investigated. The optimal reaction conditions for the coupling reaction were PdCl2(dppf)\\/NaO-t-Bu\\/toluene.

  3. Carbon11 pb-12: an attempt to visualize the dopamine d 4 receptor in the primate brain with positron emission tomography

    Microsoft Academic Search

    Oliver Langer; Christer Halldin; Yuan-Hwa Chou; Johan Sandell; Carl-Gunnar Swahn; Kjell Någren; Roberto Perrone; Francesco Berardi; Marcello Leopoldo; Lars Farde

    2000-01-01

    The dopamine D4 receptor (D4R) is expressed in low density in various extrastriatal brain regions. This receptor subtype is discussed in relation to the pathophysiology and treatment of schizophrenia but no selective positron emission tomography (PET) ligand is available to date to study the distribution in vivo. The arylpiperazine derivative N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (PB-12) is a novel, high-affinity ( Ki=0.040 nM) and

  4. Optical Resolution of ?-Amino Acids by Reverse Osmosis using Enantioselective Polymer Membrane Containing Chiral Metal-Schiff Base Complex

    Microsoft Academic Search

    Kripal Singh; Pravin G. Ingole; H. C. Bajaj; Amit Bhattacharya; Harshad R. Brahmbhatt

    2010-01-01

    The optical resolution of ?-amino acids, arginine and alanine was performed by reverse osmosis at 517.10 kPa and 1034.21 kPa pressures using enantioselective composite nanofiltration membrane prepared by interfacial co-polymerizing, a mixture of Zinc metal Schiff's base complex and piperazine with trimesoyl chloride in-situ on the top of polysulfone ultrafiltration membrane. The chemical composition of the enantioselective layer was determined by ATR-FTIR

  5. Effects of trimetazidine on in vivo coronary arterial platelet thrombosis

    Microsoft Academic Search

    Philip R. Belcher; Angela J. Drake-Holland; John W. Hynd; Mark I. M. Noble

    1993-01-01

    We used Folts' model of critical coronary artery stenosis with endothelial damage, which measures platelet-rich thrombus accumulation from cyclic flow reductions (CFRs). This paper reports results applied to trimetazidine, a member of the piperazine group. Trimetazidine at a dose of 1 mg\\/kg completely abolished CFRs caused by accumulating thrombus in the circumflex coronary artery in 4 of 8 open-chest anesthetized

  6. Effect of histamine H 4 receptor antagonist on allergic rhinitis in mice

    Microsoft Academic Search

    Yuji Takahashi; Yoto Kagawa; Kana Izawa; Rie Ono; Masaaki Akagi; Chiaki Kamei

    2009-01-01

    The aim of this study was to clarify the effect of histamine H4 receptor antagonist, JNJ7777120 (1-[(5-Chloro-1H-indol-2-yl)carbonyl]-4-methyl-piperazine) on allergic rhinitis in mice. We measured allergic symptoms (sneezing and nasal rubbing), serum total IgE and the levels of cytokines in nasal lavage fluid. Histamine H4 receptor antagonist, JNJ7777120, caused the dose-dependent inhibition of nasal symptoms by single and repeated intranasal administrations;

  7. The influence of the nematode Syphacia oblevata on adjuvant arthritis in the rat.

    PubMed Central

    Pearson, D J; Taylor, G

    1975-01-01

    The effect of infestation with the nematode Syphacia oblevata on adjuvant arthritis was studied in the rat. Animals with an established infestation with Syphacia were found to have a reduced incidence of arthritis after injection of Freund's complete adjuvant. Infested animals developing adjuvant arthritis were found to suffer from a less severe form of the disease than animals in which infestation had been eliminated with piperazine before immunization. PMID:1171819

  8. Investigation of the Ability of MDHS Method 25 to Determine Urethane-Bound Isocyanate Groups

    Microsoft Academic Search

    Robert P. Streicher; James E. Arnold; Charles V. Cooper; Thomas J. Fischbach

    1995-01-01

    Method 25 for the Determination of Hazardous Substances (MDHS 25) of the Health and Safety Executive of the United Kingdom attempts to identify and quantify all isocyanate species in an air sample. Isocyanate species are derivatized with 1-(2-methoxyphenyl)piperazine (MOPP) and analyzed by high-performance liquid chromatography (HPLC) with tandem ultraviolet\\/electrochemical (UV\\/EC) detection. The method identifies peaks as being isocyanate-derived if the

  9. [ 18F] p-MPPF: A Radiolabeled Antagonist for the Study of 5HT 1A Receptors with PET

    Microsoft Academic Search

    A Plenevaux; C Lemaire; J Aerts; G Lacan; D Rubins; W. P Melega; C Brihaye; C Degueldre; S Fuchs; E Salmon; P Maquet; S Laureys; P Damhaut; D Weissmann; D Le Bars; J.-F Pujol; A Luxen

    2000-01-01

    This paper summarizes the present status of the researches conducted with [18F]4-(2?-methoxyphenyl)-1-[2?-[N-(2??-pyridinyl)-p-fluorobenzamido]ethyl]-piperazine known as [18F]p-MPPF, a new 5-HT1A antagonist for the study of the serotonergic neurotransmission with positron emission tomography (PET). This includes chemistry, radiochemistry, animal data (rats, cats, and monkeys) with autoradiography and PET, human data with PET, toxicity, and metabolism.

  10. Novel, trifunctional diamine for silica coating in capillary zone electrophoresis

    Microsoft Academic Search

    Roberto Sebastiano; Cecilia Gelfi; Pier Giorgio Righetti; Attilio Citterio

    2000-01-01

    A novel compound {quaternarized piperazine [(N-methyl,N-4-iodobutyl)-N?-methylpiperazine] (QPzI)} for the coating of a silica capillary able to reduce or invert the electroosmotic flow (EOF) in capillary zone electrophoresis is reported. Unlike standard oligoamines (like spermine and tetraethylene pentamine) which are very efficient in quenching macromolecule interaction with the silica wall, but only in acidic pH ranges, QPzI acts all along the

  11. Chemically removable derivatization reagent for liquid chromatography: 2-(2-naphthoxy)ethyl 2-[1-(4-benzyl)piperazyl]ethanesulfonate 1 This work was presented in part at the annual meeting of the Pharmaceutical Society of Taiwan, Taipei, 10 December, 1995. 1

    Microsoft Academic Search

    Hsin-Lung Wu; Yun-Yaw Shyu; Hwang-Shang Kou; Su-Hwei Chen; Shou-Mei Wu; Shihn-Sheng Wu

    1997-01-01

    A new sulfonate reagent, 2-(2-naphthoxy)ethyl 2-[1-(4-benzyl)-piperazyl]ethanesulfonate, was synthesized for analytical derivatization in liquid chromatography. The reagent consists of two main moieties, i.e., one with a fluorophore (naphthoxy) for sensitive detection after being tagged to an analyte; and the other with a tertiary amino function (a substituted piperazine) that can be removed after derivatization by acid treatment. The reagent was applied

  12. Novel cyclopentadienyl tricarbonyl (99m)tc complexes containing 1-piperonylpiperazine moiety: potential imaging probes for sigma-1 receptors.

    PubMed

    Wang, Xia; Li, Dan; Deuther-Conrad, Winnie; Lu, Jie; Xie, Ying; Jia, Bing; Cui, Mengchao; Steinbach, Jörg; Brust, Peter; Liu, Boli; Jia, Hongmei

    2014-08-28

    We report the design, synthesis, and evaluation of a series of novel cyclopentadienyl tricarbonyl (99m)Tc complexes as potent ?1 receptor radioligands. Rhenium compounds 3-(4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl)propylcarbonylcyclopentadienyl tricarbonyl rhenium (10a) and 4-(4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl)butylcarbonylcyclopentadienyl tricarbonyl rhenium (10b) possessed high in vitro affinity for ?1 receptors and moderate to high selectivity for ?2 receptors and the vesicular acetylcholine transporter. Biodistribution studies in mice demonstrated high initial brain uptake for corresponding (99m)Tc derivatives [(99m)Tc]23 and [(99m)Tc]24 of 2.94 and 2.13% injected dose (ID)/g, respectively, at 2 min postinjection. Pretreatment of haloperidol significantly reduced the radiotracer accumulation of [(99m)Tc]23 or [(99m)Tc]24 in the brain. Studies of the cellular uptake of [(99m)Tc]23 in C6 and DU145 tumor cells demonstrated a reduction of accumulation by incubation with haloperidol, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine (SA4503), or 1,3-di-o-tolyl-guanidine (DTG). Furthermore, blocking studies in C6 glioma-bearing mice confirmed the specific binding of [(99m)Tc]23 to ?1 receptors in the tumor. PMID:25073047

  13. Targeting tumor hypoxia with 2-nitroimidazole-indocyanine green dye conjugates

    NASA Astrophysics Data System (ADS)

    Xu, Yan; Zanganeh, Saeid; Mohammad, Innus; Aguirre, Andres; Wang, Tianheng; Yang, Yi; Kuhn, Liisa; Smith, Michael B.; Zhu, Quing

    2013-06-01

    Tumor hypoxia is a major indicator of treatment resistance to chemotherapeutic drugs, and fluorescence optical tomography has tremendous potential to provide clinically useful, functional information by identifying tumor hypoxia. The synthesis of a 2-nitroimidazole-indocyanine green conjugate using a piperazine linker (piperazine-2-nitroimidazole-ICG) capable of robust fluorescent imaging of tumor hypoxia is described. In vivo mouse tumor imaging studies were completed and demonstrate an improved imaging capability of the new dye relative to an earlier version of the dye that was synthesized with an ethanolamine linker (ethanolamine-2-nitroimidazole-ICG). Mouse tumors located at imaging depths of 1.5 and 2.0 cm in a turbid medium were imaged at various time points after intravenous injection of the dyes. On average, the reconstructed maximum fluorescence concentration of the tumors injected with piperazine-2-nitroimidazole-ICG was twofold higher than that injected with ethanolamine-2-nitroimidazole-ICG within 3 h postinjection period and 1.6 to 1.7 times higher beyond 3 h postinjection. The untargeted bis-carboxylic acid ICG completely washed out after 3 h postinjection. Thus, the optimal window to assess tumor hypoxia is beyond 3 h postinjection. These findings were supported with fluorescence images of histological sections of tumor samples and an immunohistochemistry technique for identifying tumor hypoxia.

  14. Synthesis and evaluation of in vivo activity of diphenylhydantoin basic derivatives.

    PubMed

    Dylag, Tomasz; Zygmunt, Ma?gorzata; Maciag, Dorota; Handzlik, Jadwiga; Bednarski, Marek; Filipek, Barbara; Kie?-Kononowicz, Katarzyna

    2004-12-01

    During the search for antiarrhythmic agents among amide derivatives of phenytoin, compound 7 {3-ethyl-1-[2-hydroxy-3-(4-phenyl-piperazin-1-yl)-propyl]-2,4-dioxo-5,5-diphenyl-imidazolidine} was selected as it showed antiarrhythmic as well as antihypertensive activity. Treating this compound as a lead, new derivatives 8-19 were synthesised, differing in piperazine phenyl ring substitution (2-, 3-, 4-Cl, 2-CH3O) as well as in hydantoin N3 alkyl chain (ethyl, ethyl acetate or ethyl 2-propionate). The obtained compounds in form of hydrochlorides 7a-19a were examined for prophylactic antiarrhythmic and antihypertensive properties. Compounds containing ethyl 2-propionate moiety (17a, 18a) exhibited the highest antihypertensive properties. Water-soluble compounds, containing 2-methoxyphenylpiperazine group (11a, 19a), showed strong antiarrhythmic properties in adrenaline-induced arrhythmia; compound 9a {1-[3-(4-(3-chloro-phenyl)-piperazin-1-yl)- 2-hydroxy-propyl]- 3-ethyl-2,4-dioxo-5,5-diphenyl-imidazolidine hydrochloride} exhibited the highest antiarrhythmic activity in barium chloride arrhythmia model. PMID:15571863

  15. Synthesis, magnetism, and 57Fe Mössbauer spectroscopic study of a family of [Ln3Fe7] coordination clusters (Ln = Gd, Tb, and Er).

    PubMed

    Abbas, Ghulam; Lan, Yanhua; Mereacre, Valeriu; Buth, Gernot; Sougrati, Moulay T; Grandjean, Fernande; Long, Gary J; Anson, Christopher E; Powell, Annie K

    2013-10-21

    The reaction of N-methydiethanolamine (mdeaH2), benzoic acid, FeCl3, and Ln(NO3)3·6H2O or LnCl3·xH2O yields a series of decanuclear coordination clusters, [Ln3Fe7(?4-O)2(?3-OH)2(mdea)7(?-benzoate)4(N3)6]·4MeCN·H2O, where Ln = Gd(III) (1) or Tb(III) (2), and [Er3Fe7(?4-O)2(?3-OH)2(mdea)7(?-benzoate)4(N3)5(MeOH)]Cl·7.5H2O·11.5MeOH (3). The isostructural compounds 1-3 all crystallize isotypically in the triclinic space group P1? with Z = 2, as does the previously reported dysprosium analogue 4. Six of the Fe(III) ions are pseudooctahedrally coordinated, whereas the seventh has a trigonal-bipyramidal coordination geometry. Temperature-dependent direct-current magnetic susceptibility studies indicate that intracluster antiferromagnetic interactions are dominant in 1-3. The frequency-dependent out-of-phase (??) alternating-current susceptibility reveals that 2 undergoes a slow relaxation of its magnetization, presumably resulting from anisotropy of the Tb(III) ions. Between 30 and 295 K, the (57)Fe Mössbauer spectra reveal paramagnetic behavior with six partially resolved quadrupole doublets, one for the trigonal-bipyramidal Fe(III) site and five for the six pseudooctahedral Fe(III) sites. The Mössbauer spectra of 2 and 3 obtained between 3 and 30 K are consistent with the presence of Fe(III) intracluster antiferromagnetic coupling with slow magnetic relaxation relative to the Larmor precession time. Further, the observed changes in the effective magnetic field values in the spectra measured at 3 K with increasing applied field are consistent with the effect of the local spin polarization along the applied magnetic field direction, a behavior reminiscent of antiparallel spin-coupled iron molecular paramagnetic systems. PMID:24089701

  16. Paper spray and extraction spray mass spectrometry for the direct and simultaneous quantification of eight drugs of abuse in whole blood.

    PubMed

    Espy, Ryan D; Teunissen, Sebastiaan Frans; Manicke, Nicholas E; Ren, Yue; Ouyang, Zheng; van Asten, Arian; Cooks, R Graham

    2014-08-01

    Determination of eight drugs of abuse in blood has been performed using paper spray or extraction spray mass spectrometry in under 2 min with minimal sample preparation. A method has been optimized for quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), morphine, cocaine, and ?9-tetrahydrocannabinol (THC) from a single blood spot. Sample to sample variations of 1-5% relative standard deviation were achieved using stable isotope-labeled internal standards and tandem mass spectrometry. Limits of detection for all drugs were below typical physiological and toxicological levels. Paper spray and extraction spray each used less than 10 ?L of whole blood. These methods exhibit the potential for performing rapid and high-throughput assays for selective on-site multicompound quantitative screening of illicit drugs. PMID:24970379

  17. pH dependent efflux of methamphetamine derivatives and their reversal through human Caco-2 cell monolayers.

    PubMed

    Crowe, Andrew; Diep, Susanna

    2008-09-11

    The purpose of this study was to investigate possible efflux mechanisms involved in amphetamine derivative transport such as for 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), para-methoxyamphetamine (p-MA), dexamphetamine and pseudoephedrine, especially across pH gradients that exist in intestinal or kidney transport. This was determined using our Caco-2 subclone, CLEFF9. Transport of the amphetamine derivatives was evaluated at pH 7.4 and pH 6/7.4+/-efflux inhibitors. Na+-H+ transporter inhibition via carbonyl cyanide-4-trifluoromethoxy phenylhydrazone (FCCP), and metabolic inhibition using Na-azide and Na-orthovanadate were also conducted, as well as using noradrenalin, adrenalin and other inhibitors of a range of carrier mediated transport systems such as histamine, organic cation transporters and dopamine carrier systems. At pH 7.4, the rate of transport for dexamphetamine, pseudoephedrine and MDMA in both apical to basolateral and reverse directions was all very rapid, confirming extensive passive diffusion at systemic pH. However, creating a pH 6.0/7.4 gradient showed marked increase in basolateral to apical transport of all amphetamines tested, with dexamphetamine, MDEA, MDMA and p-MA having a net efflux ratio of around 16, 14, 13 and 11 respectively and this was not reversed with P-glycoprotein inhibitors. Azide, FCCP, adrenalin, noradrenalin and reserpine were able to reduce the efflux by 2 to 3 fold, although tetraethylammonium could not. This suggested that extraneuronal monoamine transporters (hEMT) could be involved. This data suggests that elevated endogenous adrenalin levels may reduce amphetamine removal from the body based on these in vitro studies. Also, the use of stomach acid lowering drugs could result in more rapid systemic uptake of these amphetamine derivatives. PMID:18638470

  18. Interactions of anthelmintic drugs in Caenorhabditis elegans neuro-muscular ion channel mutants.

    PubMed

    Miltsch, Sandra M; Krücken, Jürgen; Demeler, Janina; Ramünke, Sabrina; Harder, Achim; von Samson-Himmelstjerna, Georg

    2013-12-01

    Due to the increasing development of anthelmintic resistance in nematodes worldwide, it is important to search for anthelmintic compounds with new modes of action and also to investigate the possibility to combine compounds with possible synergistic effects. There might also be the chance to take advantage of the fact that nematode populations which have developed resistance against one anthelmintic class might respond hypersusceptibly to another drug class. The aim of this study was to investigate responses of Caenorhabditis elegans populations with mutations in neuro-muscular ion channels to different anthelmintic classes. Furthermore, potential synergistic effects between two anthelmintic compounds from different classes, i.e. emodepside and tribendimidine, were studied. Although there was neither a synergistic nor an antagonistic effect between emodepside and tribendimidine, other types of interactions could be identified. The C. elegans GABAA-receptor (GABAA-R) unc-49 mutants, showing decreased emodepside susceptibility, were more susceptible to tribendimidine than wild-type C. elegans. In contrast, the reverse phenomenon - hypersusceptibility to emodepside in tribendimidine resistant acetylcholine-receptor (AChR) loss of function mutants - was not observed. Moreover, the slo-1 mutant strain (completely emodepside resistant) also showed hypersusceptibility to piperazine. Interestingly, neither the GABAA-R unc-49 mutants nor the AChR mutants showed decreased susceptibility against piperazine, although there were some studies that indicated an involvement of GABAA-R or AChR in the piperazine mode of action. In conclusion, the present study provides evidence suggesting that interactions between commercially available anthelmintic drugs with different modes of action might be a relatively common phenomenon but this has to be carefully worked out for each anthelmintic and each anthelmintic drug combination. Moreover, results obtained in C. elegans will have to be confirmed using parasitic nematodes in the future. PMID:23707730

  19. Caenorhabditis elegans Neuromuscular Junction: GABA Receptors and Ivermectin Action

    PubMed Central

    Hernando, Guillermina; Bouzat, Cecilia

    2014-01-01

    The prevalence of human and animal helminth infections remains staggeringly high, thus urging the need for concerted efforts towards this area of research. GABA receptors, encoded by the unc-49 gene, mediate body muscle inhibition in Caenorhabditis elegans and parasitic nematodes and are targets of anthelmintic drugs. Thus, the characterization of nematode GABA receptors provides a foundation for rational anti-parasitic drug design. We therefore explored UNC-49 channels from C. elegans muscle cultured cells of the first larval stage at the electrophysiological and behavioral levels. Whole-cell recordings reveal that GABA, muscimol and the anthelmintic piperazine elicit macroscopic currents from UNC-49 receptors that decay in their sustained presence, indicating full desensitization. Single-channel recordings show that all drugs elicit openings of ?2.5 pA (+100 mV), which appear either as brief isolated events or in short bursts. The comparison of the lowest concentration required for detectable channel opening, the frequency of openings and the amplitude of macroscopic currents suggest that piperazine is the least efficacious of the three drugs. Macroscopic and single-channel GABA-activated currents are profoundly and apparently irreversibly inhibited by ivermectin. To gain further insight into ivermectin action at C. elegans muscle, we analyzed its effect on single-channel activity of the levamisol-sensitive nicotinic receptor (L-AChR), the excitatory receptor involved in neuromuscular transmission. Ivermectin produces a profound inhibition of the frequency of channel opening without significant changes in channel properties. By revealing that ivermectin inhibits C. elegans muscle GABA and L-AChR receptors, our study adds two receptors to the already known ivermectin targets, thus contributing to the elucidation of its pleiotropic effects. Behavioral assays in worms show that ivermectin potentiates piperazine-induced paralysis, thus suggesting that their combination is a good strategy to overcome the increasing resistance of parasites, an issue of global concern for human and animal health. PMID:24743647

  20. Zinc(II) complexation by some biologically relevant pH buffers.

    PubMed

    Wyrzykowski, D; Tesmar, A; Jacewicz, D; Pranczk, J; Chmurzy?ski, L

    2014-12-01

    The isothermal titration calorimetry (ITC) technique supported by potentiometric titration data was used to study the interaction of zinc ions with pH buffer substances, namely 2-(N-morpholino)ethanesulfonic acid (Mes), piperazine-N,N'-bis(2-ethanesulfonic acid) (Pipes), and dimethylarsenic acid (Caco). The displacement ITC titration method with nitrilotriacetic acid as a strong, competitive ligand was applied to determine conditional-independent thermodynamic parameters for the binding of Zn(II) to Mes, Pipes, and Caco. Furthermore, the relationship between the proposed coordination mode of the buffers and the binding enthalpy has been discussed. PMID:25319620

  1. Stereoselective Synthesis of Saturated Heterocycles via Pd-Catalyzed Alkene Carboetherification and Carboamination Reactions

    PubMed Central

    Wolfe, John P.

    2009-01-01

    The development of Pd-catalyzed carboetherification and carboamination reactions between aryl/alkenyl halides and alkenes bearing pendant heteroatoms is described. These transformations effect the stereoselective construction of useful heterocycles such as tetrahydrofurans, pyrrolidines, imidazolidin-2-ones, isoxazolidines, and piperazines. The scope, limitations, and applications of these reactions are presented, and current stereochemical models are described. The mechanism of product formation, which involves an unusual intramolecular syn-insertion of an alkene into a Pd-Heteroatom bond is also discussed in detail. PMID:19183704

  2. DNA specific fluorescent symmetric dimeric bisbenzimidazoles DBP(n): The synthesis, spectral properties, and biological activity.

    PubMed

    Ivanov, Alexander A; Koval, Vasiliy S; Susova, Olga Yu; Salyanov, Victor I; Oleinikov, Vladimir A; Stomakhin, Andrey A; Shalginskikh, Natalya A; Kvasha, Margarita A; Kirsanova, Olga V; Gromova, Elizaveta S; Zhuze, Alexei L

    2015-07-01

    A series of new fluorescent symmetric dimeric bisbenzimidazoles DBP(n) bearing bisbenzimidazole fragments joined by oligomethylene linkers with a central 1,4-piperazine residue were synthesized. The complex formation of DBP(n) in the DNA minor groove was demonstrated. The DBP(n) at micromolar concentrations inhibit in vitro eukaryotic DNA topoisomerase I and prokaryotic DNA methyltransferase (MTase) M.SssI. The DBP(n) were soluble well in aqueous solutions and could penetrate cell and nuclear membranes and stain DNA in live cells. The DBP(n) displayed a moderate effect on the reactivation of gene expression. PMID:25987376

  3. Discovery of LASSBio-772, a 1,3-benzodioxole N-phenylpiperazine derivative with potent alpha 1A\\/D-Adrenergic receptor blocking properties

    Microsoft Academic Search

    Luiz A. S. Romeiro; Marcos da Silva Ferreira; Leandro L. da Silva; Helena C. Castro; Ana L. P. Miranda; Cláudia L. M. Silva; François Noël; Jéssica B. Nascimento; Claudia V. Araújo; Eduardo Tibiriçá; Eliezer J. Barreiro; Carlos A. M. Fraga

    2011-01-01

    We described herein the discovery of 1-(2-(benzo[d] [1,3]dioxol-6-yl)ethyl)-4-(2-methoxyphenyl) piperazine (LASSBio-772), as a novel potent and selective alpha 1A\\/1D adrenoceptor (AR) antagonist selected after screening of functionalized N-phenylpiperazine derivatives in phenylephrine-induced vasoconstriction of rabbit aorta rings. The affinity of LASSBio-772 for alpha 1A and alpha 1B AR subtypes was determined through displacement of [3H]prazosin binding. We obtained Ki values of 0.14 nM

  4. Characterization of the solubility and solid-state properties of saccharin salts of fluoroquinolones.

    PubMed

    Romañuk, Carolina B; Manzo, Ruben H; Linck, Yamila Garro; Chattah, Ana K; Monti, Gustavo A; Olivera, Maria E

    2009-10-01

    Saccharinates salts of the fluoroquinolone antibiotics norfloxacin, ciprofloxacin, ofloxacin, and enrofloxacin were obtained as pure crystalline anhydrous solids with sweet taste. The products were characterized by one- ((13)C) and two-dimensional ((1)H-(13)C) dimensions solid state Nuclear Magnetic Resonance and infrared spectroscopy showing ionic interactions between the saccharine amide and the fluoroquinolone piperazine. Several intermolecular bindings were also identified. Thermal behavior and powder X-ray diffraction provided complementary evidences of salt formation. The series of products showed improved properties with respect to water solubility. A solubility model was developed. These salts would be a good way forward to developing more suitable formulations of these APIs. PMID:19226631

  5. Investigation of the inhibiting action of O-, S- and N-dithiocarbamato(1,4,8,11-tetraazacyclotetradecane)cobalt(III) complexes on the corrosion of iron in HClO 4 acid

    Microsoft Academic Search

    K. Babic-Samardzija; K. F. Khaled; N. Hackerman

    2005-01-01

    The inhibiting properties of four macrocyclic cobalt(III) complexes of the general formula [CoIII(Rdtc)cyclam](ClO4)2, where cyclam and Rdtc? refer to 1,4,8,11-tetraazacyclotetradecane and morpholine-, thiomorpholine-, piperazine-, N-methylpiperazine-dithiocarbamates, respectively, has been studied on the corrosion of iron in aerated 0.1M HClO4 solutions by potentiodynamic polarization (dc) technique and electrochemical impedance spectroscopy (ac). Inhibitor efficiency for the corrosion of iron is found to be

  6. The novel, selective, brain-penetrant neuropeptide Y Y2 receptor antagonist, JNJ-31020028, tested in animal models of alcohol consumption, relapse, and anxiety

    Microsoft Academic Search

    Andrea Cippitelli; Amir H. Rezvani; J. Elliott Robinson; Lindsay Eisenberg; Edward D. Levin; Pascal Bonaventure; S. Timothy Motley; Timothy W. Lovenberg; Markus Heilig; Annika Thorsell

    2011-01-01

    Neuropeptide Y (NPY) signaling has been shown to modulate stress responses and to be involved in regulation of alcohol intake and dependence. The present study explores the possibility that blockade of NPY Y2 autoreceptors using a novel, blood–brain barrier penetrant NPY Y2 receptor antagonist, JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2-pyridin-3-ylbenzamide), may achieve a therapeutically useful activation of the NPY system in alcohol- and anxiety-related

  7. Paraherquamide e.

    PubMed

    Aree, Thammarat; Antia, Bassey S; Ekpa, Okon D; Kittakoop, Prasat

    2010-01-01

    In the title compound, C(28)H(35)N(3)O(4), also known as 14-de-oxy-paraherquamide A,the two pyrrolidine rings adopt envelope conformations. The piperazine ring of the diaza-bicyclo-[2.2.2]octan-3-one unit adopts a boat conformation whereas the two piperidine rings are in distorted boat conformations. Intra-molecular C-H?O hydrogen bonds are observed. In the crystal, the mol-ecules are linked into chains along the b axis by inter-molecular N-H?O hydrogen bonds. PMID:21588597

  8. Paraherquamide E

    PubMed Central

    Aree, Thammarat; Antia, Bassey S.; Ekpa, Okon D.; Kittakoop, Prasat

    2010-01-01

    In the title compound, C28H35N3O4, also known as 14-de­oxy­paraherquamide A,the two pyrrolidine rings adopt envelope conformations. The piperazine ring of the diaza­bicyclo­[2.2.2]octan-3-one unit adopts a boat conformation whereas the two piperidine rings are in distorted boat conformations. Intra­molecular C—H?O hydrogen bonds are observed. In the crystal, the mol­ecules are linked into chains along the b axis by inter­molecular N—H?O hydrogen bonds. PMID:21588597

  9. Disruption of Unprecedented B?H…M Agostic Interactions: An Alternative Approach for Labeling Bioactive Molecules

    Microsoft Academic Search

    R. Garcia; A. Paulo; A. Domingos; I. Santos

    2005-01-01

    The agostic B?H…Re bond in complexes [Re{??R(??H)B(tim)2}(CO)3] (R=H (1), Ph (2), tim?=?2?mercapto?1?methylimidazolyl) is readily cleaved by t?butylisonitrile or cyclohexylisonitrile leading to the mixed?ligand complexes [Re{??Ph(??H)B(tim)2}(C?NBu)(CO)3] (3) and [Re{??H(??H)B(tim)2}(C?N?cyclohexyl)(CO)3] (4), respectively. Bearing in mind the so?called [2?+?1] mixed ligand approach for the development of target?pecific radiopharmaceuticals, reactions of 1 with isonitriles carrying the (2?methoxyphenyl)piperazine pharmacophore (part of WAY 100635) were also

  10. Synthesis and in vivo evaluation of [ 11C]SA6298 as a PET sigma 1 receptor ligand

    Microsoft Academic Search

    Kazunori Kawamura; Kiichi Ishiwata; Hisashi Tajima; Shin-Ichi Ishii; Yuhei Shimada; Kiyoshi Matsuno; Yoshio Homma; Michio Senda

    1999-01-01

    The potential of a 11C-labeled selective sigma1 receptor ligand, 1-(3,4-dimethoxyphenethyl)-4-[3-(3,4-dichlorophenyl)propyl]piperazine ([11C]SA6298), was evaluated as a positron emission tomography (PET) ligand for mapping sigma1 receptors in the central nervous system and peripheral organs. [11C]SA6298 was synthesized by methylation of the desmethyl SA6298 with [11C]CH3I, with the decay-corrected radiochemical yield of 39 ± 5% based on [11C]CH3I and with the specific activity

  11. In vivo evaluation of [ 11C]SA4503 as a PET ligand for mapping CNS sigma 1 receptors

    Microsoft Academic Search

    Kazunori Kawamura; Kiichi Ishiwata; Hisashi Tajima; Shin-Ichi Ishii; Kiyoshi Matsuno; Yoshio Homma; Michio Senda

    2000-01-01

    The potential of the 11C-labeled selective sigma1 receptor ligand 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([11C]SA4503) was evaluated in vivo as a positron emission tomography (PET) ligand for mapping sigma1 receptors in rats. SA4503 is known to have a high affinity (IC50 = 17.4 nM) and a higher selectivity (sigma1\\/sigma2 = 103) for the sigma1 receptor. A high and increasing brain uptake of [11C]SA4503 was

  12. Age-related changes of the binding of [ 3 H]SA4503 to sigma 1 receptors in the rat brain

    Microsoft Academic Search

    Kiichi Ishiwata; Tadayuki Kobayashi; Kazunori Kawamura; Kiyoshi Matsuno

    2003-01-01

    We have recently developed 1-([3-O-methyl-11C]3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine ([11C]SA4503) as a selective radioligand for mapping sigma1 receptors in the brain by positron emission tomography (PET). In the present short communication we evaluated the agerelated\\u000a changes of the binding of this ligand to sigma1 receptors in Fisher-344 rats (1.5-, 6-, 12-, and 24-month-old) by thein vitro binding assay. We also measured the binding

  13. Preclinical evaluation of [ 11 C]SA4503: radiation dosimetry, in vivo selectivity and PET imaging of sigma 1 receptors in the cat brain

    Microsoft Academic Search

    Kazunori Kawamura; Kiichi Ishiwata; Yuhei Shimada; Yuichi Kimura; Tadayuki Kobayashi; Kiyoshi Matsuno; Yoshio Homma; Michio Senda

    2000-01-01

    Our previousin vivo study with rats has demonstrated that11C-labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([11C]SA4503) is a potential radioligand for mapping CNS sigma1 receptors by positron emission tomography (PET). In the present study, we further characterized this ligand. The radiation\\u000a absorbed-dose of [11C]SA4503 in humans estimated with the tissue distribution in mice, was higher in the liver, kidney and pancreas than in other\\u000a organs

  14. Inhibition of poly(ADP-ribose) polymerase prevents irinotecan-induced intestinal damage and enhances irinotecan\\/temozolomide efficacy against colon carcinoma

    Microsoft Academic Search

    Lucio Tentori; Carlo Leonetti; Marco Scarsella; Alessia Muzi; Emanuela Mazzon; Matteo Vergati; Olindo Forini; Rena Lapidus; Weizheng Xu; Annalisa Susanna Dorio; Jie Zhang; Salvatore Cuzzocrea; Grazia Graziani

    2006-01-01

    Poly(ADP-ribose) polymerase (PARP) in- hibitors enhance the antitumor activity of the topoisom- erase I inhibitor irinotecan (CPT-11), which is used to treat advanced colorectal carcinoma. Since PARP inhibi- tors sensitize tumor cells also to the methylating agent temozolomide (TMZ) and clinical trials are evaluating CPT-11 in combination with TMZ, we tested whether the PARP inhibitor GPI 15427 (10-(4-methyl-piperazin-1-ylm- ethyl)-2H-7-oxa-1,2-diaza-benzo(de)anthracen-3-one) in-

  15. [ 3 H]Serotonin binding sites in goldfish retinal membranes

    Microsoft Academic Search

    Lucimey Lima; Isabelle Radtke; Boris Drujan

    1992-01-01

    Serotonin (5HT) binding sites were studied in goldfish retinal membranes by radioligand experiments. The binding site of [3H]5HT was sensitive to pre-treatment of the membranes at 40° or 60° C. 5HT and 5-methoxy-N,N-dimethyltryptamine were the best inhibitors of [3H]5HT binding to retinal membranes. The 5HT2 agonist, 1-(-naphtyl)piperazine, was also a potent inhibitor, however, (+)-1-2,5-dimethoxy-4-iodopheny1-2-aminopropane was less efficient. The catecholaminergic agents

  16. A solvent-free sampling method for airborne toluene diisocyanate

    Microsoft Academic Search

    A. Robert; P. Simon

    1987-01-01

    Summary  A useful method of sampling and measurement of toluene diisocyanate concentration in atmosphere is described. The sampler\\u000a consists of glass-fibre filters impregnated with the reagent 1-(2-methoxyphenyl)piperazine1 so that the 2,4 and 2,6 isomers of TDI react to form urea derivatives which are analysed by high performance liquid chromatography\\u000a in isocratic mode on cyan-amino and C18 bonded phases. A dynamic system

  17. A ferroelectric olefin-copper(I) organometallic polymer with flexible organic ligand (R)-MbVBP

    NASA Astrophysics Data System (ADS)

    Wang, Guo-Xi; Xing, Zheng; Chen, Li-Zhuang; Han, Guang-Fan

    2015-07-01

    Hydrothermal treatment of (R)-2-methyl-1,4-bis(4-vinylbenzyl)piperazine [(R)-MbVBP] and CuCl afforded a novel olefin-copper(I) coordination compound. Introducing the flexible ligand (R)-MbVBP allowed the olefin-copper(I) organometallic compound to crystallize in a polar point group P21. The compound was ferroelectric, and its electric hysteresis loop showed a remnant polarization (Pr) of 0.13-0.32 ?C cm-2 and a coercive field (Ec) of 3.5-11 kV cm-1.

  18. 5HT 1A receptor antagonists increase the activity of serotonergic cells in the dorsal raphe nucleus in rats treated acutely or chronically with citalopram

    Microsoft Academic Search

    Lotta Arborelius; George G. Nomikos; Pernilla Grillner; Peter Hertel; Berit Backlund Höök; Uli Hacksell; Torgny H. Svensson

    1995-01-01

    In this study we have examined the acute effects of systemic administration of the selective serotonin reuptake inhibitor (SSRI), citalopram, in combination with either of the two selective 5-HT1A receptor antagonists, (S)-5-fluoro-8-hydroxy-2-(dipropylamino)-tetralin [(S)-UH-301] or (+)-N-tertbutyl 3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropionamide dihydrochloride [(+)-WAY100135], on the activity of single 5-HT neurons in the dorsal raphe nucleus (DRN) of anesthetized rats using extracellular recording techniques. Acute administration

  19. Asymmetric hetero-Diels-Alder reaction of diazenes catalyzed by chiral silver phosphate: water participates in the catalysis and stereocontrol.

    PubMed

    Liu, Bin; Liu, Tong-Yu; Luo, Shi-Wei; Gong, Liu-Zhu

    2014-12-01

    The chiral silver phosphate was confirmed to efficiently catalyze a highly regio- and enantioselective hetero-Diels-Alder reaction of diazenes to furnish piperazine derivatives in high yields and excellent ee values. DFT calculations revealed that the water molecule participates in the catalysis by coordination to silver phosphate and also found that the hydroxy group of 1-hydroxy-2,3-hexadiene not only formed a hydrogen bond with the oxygen of phosphate but also coordinated to the Ag(I) to simultaneously stabilize the transition states and control the regioselectivity. PMID:25409286

  20. 4-(4-Chloro­phen­yl)-4-hy­droxy­piperidinium benzoate

    PubMed Central

    Jasinski, Jerry P.; Golen, James A.; Siddaraju, B. P.; Dayananda, A. S.; Yathirajan, H. S.

    2011-01-01

    In the title salt, C11H15ClNO+·C7H5O2 ?, the dihedral angle between the mean planes of the chloro­phenyl ring of the cation and the benzene ring of the anion is 74.4?(1)°. In the cation, the six-membered piperazine ring adopts a chair conformation. The crystal packing is stabilized by inter­molecular N—H?O and O—H?O hydrogen bonds, and weak inter­molecular C—H?O, C—H?Cl and C—H?? inter­actions. PMID:21754814

  1. 4-(4-Chloro-phen-yl)-4-hy-droxy-piperidinium benzoate.

    PubMed

    Jasinski, Jerry P; Golen, James A; Siddaraju, B P; Dayananda, A S; Yathirajan, H S

    2011-06-01

    In the title salt, C(11)H(15)ClNO(+)·C(7)H(5)O(2) (-), the dihedral angle between the mean planes of the chloro-phenyl ring of the cation and the benzene ring of the anion is 74.4?(1)°. In the cation, the six-membered piperazine ring adopts a chair conformation. The crystal packing is stabilized by inter-molecular N-H?O and O-H?O hydrogen bonds, and weak inter-molecular C-H?O, C-H?Cl and C-H?? inter-actions. PMID:21754814

  2. Selective dendritic fluorescent sensors for Zn(II).

    PubMed

    Wang, Feng; Peng, Ruogu; Sha, Yaowu

    2008-01-01

    A series of dendritic 8-hydroxyquinoline (8-HQ) and 5-dialkyl(aryl)aminomethyl-8-HQ derivatives were synthesized and their fluoroionophoric properties toward representative alkali, alkaline earth, group IIIA and transition metal ions were investigated. Among the selected ions, Zn(II) enhanced the fluorescence of N-di-(methoxycarbonylethyl)aminoethyl-3-[4-(8-hydroxyquinolin-5-ylmethyl)piperazin-1-yl]-propanoic amide] (7) by 31-fold, while Al(III) caused enhancement to some extent. The absence of any significant fluorescence enhancement by the other ions examined renders 7a highly useful Zn(II)-selective fluorescent sensor. PMID:18463593

  3. The buffering-out effect and phase separation in aqueous solutions of EPPS buffer with 1-propanol, 2-propanol, or 2-methyl-2-propanol at T = 298.15 K

    Microsoft Academic Search

    Mohamed Taha; Han-Lan Teng; Ming-Jer Lee

    Buffering-out is a new liquid–liquid phase separation phenomenon observed in mixtures containing a buffer as a mass separating agent. The (liquid+liquid) equilibrium (LLE) and (solid+liquid+liquid) equilibrium (SLLE) data were measured for the ternary systems {3-[4-(2-hydroxyethyl)piperazin-1-yl]propanesulfonic acid (EPPS) buffer+1-propanol, 2-propanol, or 2-methyl-2-propanol+water} at T=298.15K under atmospheric pressure. The phase boundary data were fitted to an empirical equation relating to the concentrations

  4. Possible pharmacokinetic and pharmacodynamic factors affecting parkinsonism inducement by cinnarizine and flunarizine.

    PubMed

    Kariya, S; Isozaki, S; Masubuchi, Y; Suzuki, T; Narimatsu, S

    1995-11-01

    Potentialities of cinnarizine [1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)piperazine, CZ] and its fluorine derivative flunarizine [1-[bis(4-fluorophenyl)-methyl]-4-(3-phenyl-2-propenyl)piperazine, FZ] to induce parkinsonism as an adverse effect were evaluated pharmacokinetically and pharmacodynamically in rats. In multiple-dose experiments, CZ or FZ was given to rats at a daily dose of 20 mumol/kg for 1, 5, 10, 15, and 30 days, and CZ, FZ, and the ring-hydroxylated metabolites of their cinnamyl moiety [1-(diphenylmethyl)-4-[3-(4'-hydroxyphenyl)-2-propenyl]piperazine, C-2 and 1-[bis(4-fluorophenyl)methyl]-4-[3-(4'- hydroxyphenyl)propenyl]piperazine, F-2] in the plasma and striatum were determined 24 hr after the final dose. Plasma and striatum concentrations of the above compounds except for FZ reached steady state after 10 doses, but their concentrations of FZ continued to increase throughout the experiments. The concentrations obtained after the 30 doses were in the order of FZ > F-2 > CZ > C-2 for the plasma and of F-2 > FZ > CZ > C-2 for the striatum. The ratios of striatum to plasma concentrations of C-2 and F-2 were 2.4 and 3 times higher than those of the parent drugs. Binding affinities of CZ, FZ, and their 10 metabolites for rat striatal dopamine D-2 receptors (D2-R) were assessed by competitive radioligand-binding studies using [3H]-N-[(2RS,3RS)-1-benzyl-2-methyl-3-pyrrolidinyl]-5-chloro-2-met hoxy- 4-methylamino-benzamide ([3H]-YM-09151-2). The IC50s calculated from their Ki values were in the order of F-2 < C-2 < FZ < CZ < C-4 < F-1, indicating that C-2 and F-2 exhibit higher affinities for D2-R than the parent drugs, whereas affinities of other metabolites were 1 to 2 orders of magnitude less than those of C-2 and F-2. These results suggest some important roles of C-2 and F-2 in the development of parkinsonism as active metabolites during chronic medication with CZ and FZ, respectively. PMID:7503767

  5. Evaluation of anthelmintic activity of nuts of Semecarpus anacardium

    PubMed Central

    Pal, Dilipkumar; Mohapatra, Tapas Kumar; Das, Apurba

    2008-01-01

    The anthelmintic activity of different extracts of nuts of Semecarpus anacardium were evaluated separately on adult Indian earthworm (Pheritima posthuma). It was found that petroleum ether, chloroform extract of S. anacardium (PESA and CESA, respectively) showed better anthelmintic activities than ethanol (EESA) and aqueous (AESA) extract of it. The anthelmintic effects of PESA and CESA at 10 mg/ml and EESA at 20 mg/ml concentration are comparable to that of the effects produced by the reference standards, albendazole (10 mg/ml) and piperazine citrate (10 mg/ml). PMID:22557277

  6. Evaluation of anthelmintic activity of nuts of Semecarpus anacardium.

    PubMed

    Pal, Dilipkumar; Mohapatra, Tapas Kumar; Das, Apurba

    2008-01-01

    The anthelmintic activity of different extracts of nuts of Semecarpus anacardium were evaluated separately on adult Indian earthworm (Pheritima posthuma). It was found that petroleum ether, chloroform extract of S. anacardium (PESA and CESA, respectively) showed better anthelmintic activities than ethanol (EESA) and aqueous (AESA) extract of it. The anthelmintic effects of PESA and CESA at 10 mg/ml and EESA at 20 mg/ml concentration are comparable to that of the effects produced by the reference standards, albendazole (10 mg/ml) and piperazine citrate (10 mg/ml). PMID:22557277

  7. Determination of D-Malate Using Immobilized D-Malate Dehydrogenase in a Flow System and its Application to Analyze the D-Malate Content of Beverages

    Microsoft Academic Search

    Hisakazu Mori; Satoshi Shiraki

    2008-01-01

    peak areas due to NADH were observed at pH 8.0 when the pH of the carrier consisting of piperazine- 1,4-bis(2-ethanesulfonic acid) (PIPES) buffer ranged from 7.0 to 8.5. Various buffer types were also ex- amined as carrier media at pH 8.0, and PIPES buffer showed the maximum peak area. When the carrier composed of PIPES buffer (0.1M, pH 8.0) contain-

  8. Hygromycin B as an anthelmintic and antibiotic for poultry 

    E-print Network

    Latif, Mohammed Abdul

    1960-01-01

    and cecal wursm. Sloan et ~al (1954) showed that a single oral administra Cion of 150 mgs. or more of piperazine adipate/kiIogram of body weight resulted in 97 to 100 percent elimination of + ~alii from chickens without affecting growth or egg production... during the growing period Effects of continuous feeding of hygromycin B dur'ing the laying period 29 Statistical comparison of the average number of eggs laid on continuous feeding of hy- gromycin B during the laying period 30 INTRORUCTION...

  9. Chemospecific and ligand free CuI catalysed heterogeneous N-arylation of amines with diheteroaryl halides at room temperature.

    PubMed

    Verma, Sanjeev K; Acharya, B N; Kaushik, M P

    2011-03-01

    A ligand free, copper-catalyzed N-arylation reaction of amines with diheteroaryl halides in heterogeneous medium at room temperature has been developed. The protocol is very effective for low boiling amines and useful for amines available in aqueous solution. The reaction gives chemospecific arylation of amines with diheteroaryl halides in the mixture monoheteroaryl halides, diheteroaryl halides and carbocyclic aryl halides. The reaction is also chemospecific with respect to arylation of aliphatic amines. Monoarylated piperazines were also synthesized at room temperature following this protocol. PMID:21218234

  10. In vivo effects of the putative cognitive enhancer KA672.HCl in comparison with 8-hydroxy-2-(DI N-propylamino) tetralin and haloperidol on dopamine, 3,4-dihydroxypheny-lacetic acid, serotonin and 5-hydroxyindoleacetic acid levels in striatal and cortical brain regions

    Microsoft Academic Search

    Peter Teismann; Boris Ferger

    2000-01-01

    1.1. KA-672.HC1 (7-methoxy-6-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propoxy]-3,4-dimethyl-2H-1-benzopyran-2-one hydrochloride), designed as a cognitive enhancer, has been investigated through behavioural and binding studies. However, little is known about its biochemical effects on the dopaminergic and serotoninergic system in vivo.2.2. In the present study the authors investigated the effects of KA-672.HCl (0. l mg\\/kg and 1 mg\\/kg) 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) (1 mg\\/kg), haloperidol (0.1 mg\\/kg) and a

  11. Labelling of recombinant human and native rat serotonin 5HT1A receptors by a novel, selective radioligand, [3H]-S 15535: Definition of its binding profile using agonists, antagonists and inverse agonists

    Microsoft Academic Search

    A. Newman-Tancredi; L. Verrièle; C. Chaput; M. J. Millan

    1998-01-01

    The novel benzodioxopiperazine, 5-HT1A receptor weak partial agonist, S 15535 (4-(benzodioxan-5-yl)1-(indan-2-yl)piperazine) bound with high affinity and selectivity\\u000a to membranes of Chinese Hamster Ovary cells stably expressing the human (h) 5-HT1A receptor (Ki = 0.6 nM versus [3H]-8-hydroxy-dipropylamino-tetralin, [3H]-8-OH-DPAT): its affinity at h5-HT1A receptors was more than 70-fold higher than its affinity at > 50 other binding sites. S 15535 was

  12. The crystal structures of three clozapinium salts: different mol­ecular configurations, and supra­molecular assembly in one, two and three dimensions

    PubMed Central

    Kaur, Manpreet; Jasinski, Jerry P.; Yathirajan, Hemmige S.; Kavitha, Channappa N.; Glidewell, Christopher

    2015-01-01

    The structures of three salts derived from clozapine, 8-chloro-11-(4-methyl­piperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine, are reported, namely, clo­za­pin­ium 3,5-di­nitro­benzoate dimethyl sulfoxide monosolvate, C18H20ClN4 +·C7H3N2O6 ?·C2H6OS, (I), where the dimethyl sulfoxide component is disordered over two sets of atomic sites having occupancies 0.627?(2) and 0.373?(2); clo­za­pin­ium hydrogen maleate 0.21-hydrate, C18H20ClN4 +·C4H3O4 ?·0.21H2O, (II), and clozapinium 2-hy­droxy­benzoate, C18H20ClN4 +·C7H5O3 ?, (III). In all three salts, the protonation site is the methyl­ated N atom of the piperazine ring, and the dimensions and conformations of the fused tricyclic system are very similar. However, differences are apparent in the piperazine component: in both compounds (II) and (III), the unprotonated N atom of this ring has a pyramidal geometry, but in compound (I) this atom has a planar geometry. In compound (III), both N-substituents in this ring occupy equatorial sites, but in compound (II) the fused tricyclic system occupies an axial site of the piperazine ring. The independent components of compound (I) are linked within the selected asymmetric unit by a combination of N—H?O and C—H?O hydrogen bonds, and these hydrogen-bonded aggregates are linked into chains by an aromatic ?–? stacking inter­action. In compound (II), the components are linked into sheets by a combination of O—H?O, N—H?O and C—H?O hydrogen bonds, and in compound (III), a combination of N—H?O, C—H?O and C—H?N hydrogen bonds links the components into a three-dimensional framework structure. Comparisons are made with some similar compounds.

  13. Inhibitory Effect of the New Orally Active CCR4 Antagonist K327 on CCR4+CD4+ T Cell Migration into the Lung of Mice with Ovalbumin-Induced Lung Allergic Inflammation

    Microsoft Academic Search

    Takashi Sato; Masato Komai; Miho Iwase; Katsuya Kobayashi; Harunobu Tahara; Etsuo Ohshima; Hitoshi Arai; Ichiro Miki

    2009-01-01

    CC chemokine receptor 4 (CCR4) is expressed on Th2 cells, found in inflamed tissues of allergic diseases, and is therefore suspected to be involved in the pathogenesis of allergic diseases by controlling Th2 cell migration into inflamed tissues. The aim of the present study was to investigate the inhibitory effect of a selective CCR4 antagonist, K327 [6-cyclopropancarbonyl-4-(2,4-dichlorobenzylamino)-2-(4-[2-(piperidin-1-yl)ethyl] piperazin-1-yl)-7,8-dihydro-5H-pyrido (4,3-d)pyrimidine], on

  14. Analysis of Ethanolamines: Validation of Semi-Volatile Analysis by HPLC-MS/MS by EPA Method MS888

    SciTech Connect

    Owens, J; Vu, A; Koester, C

    2008-10-08

    The Environmental Protection Agency's (EPA) Region 5 Chicago Regional Laboratory (CRL) developed a method titled 'Analysis of Diethanolamine, Triethanolamine, n-Methyldiethanolamine, and n-Ethyldiethanolamine in Water by Single Reaction Monitoring Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS): EPA Method MS888'. This draft standard operating procedure (SOP) was distributed to multiple EPA laboratories and to Lawrence Livermore National Laboratory, which was tasked to serve as a reference laboratory for EPA's Environmental Reference Laboratory Network (ERLN) and to develop and validate analytical procedures. The primary objective of this study was to validate and verify the analytical procedures described in 'EPA Method MS888' for analysis of the listed ethanolamines in aqueous samples. The gathered data from this validation study will be used to: (1) demonstrate analytical method performance; (2) generate quality control acceptance criteria; and (3) revise the SOP to provide a validated method that would be available for use during a homeland security event. The data contained in this report will be compiled, by EPA CRL, with data generated by other EPA Regional laboratories so that performance metrics of 'EPA Method MS888' can be determined.

  15. Photocatalytic dechlorination of PCB 138 using leuco-methylene blue and visible light; reaction conditions and mechanisms.

    PubMed

    Izadifard, Maryam; Langford, Cooper H; Achari, Gopal

    2010-09-15

    A study of dechlorination of PCB 138, under visible light employing methylene blue (MB) and triethylamine (TEA) in acetonitrile/water has been conducted to investigate the details of the mechanism of dechlorination and to determine the efficiency of the process for this representative congener. Two other amines, N-methyldiethanolamine (MEDA) and (triethanolamine) TEOA also replaced TEA and two other solvents, methanol and ethanol replacing acetonitrile were examined for effects on reaction rates. The results show that PCB 138 can be dechlorinated efficiently in this photocatalytic reaction. Clarifying ambiguities in several previous reports, the reduced form of MB, leuco-methylene blue (LMB) was identified as responsible for the photoreaction with its excited state transferring an electron to PCBs; oxidized LMB (i.e. MB) is reduced back to LMB by the excess amine present. The reaction depends on a cycle driven by the amine as a sacrificial electron donor. MEDA proved to be the most efficient electron donor; apparently in consequence of the most favourable steady state concentration of LMB. Methanol and ethanol may be used to replace acetonitrile with little change in the efficiency of the reaction. PMID:20542375

  16. NMR studies of buspirone (an anxiolytic drug) analogues

    NASA Astrophysics Data System (ADS)

    Chilmonczyk, Zdzis?aw; Cybulski, Jacek; Szelejewska-Wo?niakowska, Agnieszka; Le?, Andrzej

    1996-12-01

    Conformations of piperazine rings in 8-{4-[4-(2-pyrimidyl)-1-piperazinyl]butyl}-8-azaspiro[4.5]-decane-7,9-dione (buspir-one — 1) and its two analogues 8-{4-[4-(2-quinolinyl)-1-piperazinyl]butyl}-8-azaspiro[4.5]-decane-7,9-dione (kaspar — 2) and 4,4-dimethyl-1-{4-[4-(2-quinolinyl)-1-piperazinyl]butyl}-2,6-piperidinedione (mesmar — 3) (Fig. 1) have been studied with the aid of 1H NMR and 13C NMR spectra. For free bases the two bands corresponding to piperazine hydrogen atoms in the spectra broaden considerably with a decrease in temperature to divide into four separate bands, indicating the presence of a dynamic exchange process. A similar dynamic process, but for higher temperatures, was observed for buspirone ( 1), kaspar ( 2) and mesmar ( 3) hydrochlorides. Proton and carbon atom resonance lines have been assigned with the aid of 2D COSY and 2D HETCOR two-dimensional spectra.

  17. Screening for new psychoactive substances in hair by ultrahigh performance liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Strano-Rossi, Sabina; Odoardi, Sara; Fisichella, Marco; Anzillotti, Luca; Gottardo, Rossella; Tagliaro, Franco

    2014-11-01

    In the latest years, many new psychoactive substances (NPS) from several drug classes have appeared in the illicit drug market. Their rapid, sensitive and specific identification in biological fluids is hence of great concern for clinical and forensic toxicologists. Here is described a multi-analyte method for the determination of NPS, pertaining to different chemical classes (synthetic cannabinoids, synthetic cathinones, ketamine, piperazines and amphetamine-type substances-ATS) in human hair using ultrahigh performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) in electrospray ionization mode. We focused on a sample preparation able to extract the different classes of NPS. About 30mg of hair was decontaminated and incubated overnight under sonication in different conditions depending on the type of analytes to be extracted: (a) with 300?L of HCOOH 0.1% for cathinones, piperazines and ATS; (b) with 300?L of MeOH for synthetic cannabinoids. Ten microliter of the extracts were then injected in UHPLC-ESI-MS/MS in MRM mode. The LODs varied from 2pg/mg to 20pg/mg. The method was linear in the range from the LOQ to 500pg/mg and showed acceptable precision (%RSD<15) and accuracy (%E<15) for all the analytes. The method was finally applied on 50 samples from real forensic cases (driving license re-granting, postmortem toxicological analyses, workplace drug testing). In three samples we detected synthetic cannabinoids, in four samples cathinones or ephedrines, in two samples ketamine. PMID:25465012

  18. Blood pH optrode based on evanescent waves and refractive index change

    NASA Astrophysics Data System (ADS)

    Hammarling, Krister; Hilborn, Jöns; Nilsson, Hans-Erik; Manuilskiy, Anatoliy

    2014-02-01

    Sensing pH in blood with an silica multimode optical fiber. This sensor is based on evanescent wave absorption and measures the change of the refractive index and absorption in a cladding made of a biocompatible Polymer. In contrast to many existing fiber optical sensors which are based upon different dyes or florescent material to sense the pH, here presents a solution where a part of the cladding is replaced with a Poly (?-amino ester) made of 1.4-Butanediol diacrylate, Piperazine, and Trimethylolpropane Triacrylate. Piperazine has the feature of changing its volume by swelling or shrinking in response to the pH level. This paper utilizes this dimension effect and measure the refractive index and the absorption of the cladding in respect to different pH-levels. The alteration of refractive index also causes a change in the absorption and therefore the output power changes as a function of the pH level. The sensor is sensitive to pH in a wide spectral range and light absorbency can be observed for wavelengths ranging from UV to far IR.

  19. Discovery of N-{4-[(3-Hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2-methylpropyl}-4-phenoxybenzamide Analogues as Selective Kappa Opioid Receptor Antagonists

    PubMed Central

    Kormos, Chad M.; Jin, Chunyang; Cueva, Juan Pablo; Runyon, Scott P; Thomas, James B.; Brieaddy, Lawrence E.; Mascarella, S. Wayne; Navarro, Hernán A.; Gilmour, Brian P.; Carroll, F. Ivy

    2013-01-01

    There is continuing interest in the discovery and development of new ? opioid receptor antagonists. We recently reported that N-substituted 3-methyl-4-(3-hydroxyphenyl)piperazines were a new class of opioid receptor antagonists. In this study we report the syntheses of two piperazine JDTic-like analogues. Evaluation of the two compounds in an in vitro [35S]GTP?S binding assay showed that neither compound showed the high potency and ? opioid receptor selectivity of JDTic. A library of compounds using the core scaffold 21 was synthesized and tested for their ability to inhibit [35S]GTP?S binding stimulated by the selective ? opioid agonist U69,593. These studies led to N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyl}-2-methylpropyl]-4-phenoxybenzamide (11a), a compound that showed good ? opioid receptor antagonist properties. An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [35S]GTP?S binding assay showed that several of the analogues were potent and selective ? opioid receptor antagonists. PMID:23651437

  20. An efficient mono-component polymeric intumescent flame retardant for polypropylene: preparation and application.

    PubMed

    Shao, Zhu-Bao; Deng, Cong; Tan, Yi; Chen, Ming-Jun; Chen, Li; Wang, Yu-Zhong

    2014-05-28

    We found in our previous study that ethylenediamine- or ethanolamine-modified ammonium polyphosphates could be used alone as an intumescent flame retardant for polypropylene (PP), but their flame-retardant efficiency was not very high. In this present work, a novel highly-efficient mono-component polymeric intumescent flame retardant, piperazine-modified ammonium polyphosphate (PA-APP) was prepared. The oxygen index value of PP containing 22 wt % of PA-APP reached 31.2%, which increased by 58.4% compared with that of PP with equal amount of APP, and the vertical burning test (UL-94) could pass V-0 rating. Cone calorimeter (CC) results indicated that PP/PA-APP composite exhibited superior performance compared with PP/APP composite. For PP containing 25 wt % of PA-APP, fire growth rate (FGR) and smoke production rate (SPR) peak were reduced by 86.4% and 78.2%, respectively, compared with PP blended with 25 wt % APP. The relevant flame-retardant mechanism of PA-APP was investigated by Fourier transform infrared spectroscopy etc. The P-N-C structure with the alicyclic amine was formed during the thermal decomposition of piperazine salt (-NH2(+)-O-P-), and the rich P-N-C structure facilitated the formation of stable char layer at the later stage, consequently improving the flame-retardant efficiency of APP. PMID:24742305

  1. Antiproliferative activity of the Michael adducts of aroylacrylic acids and cyclic amines.

    PubMed

    Jurani?, Ivan O; Toši?, Ana V; Kolundžija, Branka; Drakuli?, Branko J

    2014-08-01

    Antiproliferative activity of twenty one Michael adducts of aroylacrylic acids and cyclic amines (N-Me-piperazine, imidazole, 2-Me-imidazole, and indole) was tested toward five human tumor cell lines (HeLa, LS174, K562, FemX, MDA-MB-361) in vitro. Compounds exerted antiproliferative activity in the high to the single-digit micromolar concentrations, causing increase of the cell population fraction in S phase and apoptosis. N-Me-piperazine and imidazole derivatives of aroylacrylic acids substituted with bulky alkyl substituents (2,4-di-i-Pr-Ph-, 2,4,6-tri-Et-Ph-, or ?-tetrahydronaphthyl-) showed the best potency, while indole adducts were proved as the inferior antiproliferative agents. Few compounds showed significant selectivity, tumor versus healthy cells, with selectivity index ~60 for the most selective congener. An unbiased in silico distinction between more and less potent compounds was obtained from 3D QSAR models derived by alignment-independent GRIND-2 descriptors. PMID:24874228

  2. Effect of heterocyclic based organoclays on the properties of polyimide-clay nanocomposites.

    PubMed

    Krishnan, P Santhana Gopala; Joshi, Mangala; Bhargava, Prachur; Valiyaveettil, Suresh; He, Chaobin

    2005-07-01

    Polyimide-clay nanocomposites were prepared from their precursor, namely, polyamic acid, by the solution-casting method. Organomodified montmorillonite (MMT) clay was prepared by treating Na+MMT (Kunipia F) with three different intercalating agents, namely, piperazine dihydrochloride, 1,3-bis(4-piperidinylpropane) dihydrochloride and 4,4'-bipiperidine dihydrochloride at 80 degrees C. Polyamic acid solutions containing various weight percentages of organomodified MMT were prepared by reacting 4,4'-(1,1'-biphenyl-4,4'-diyldioxy)dianiline with bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxylic dianhydride in N-methyl-2-pyrrolidinone containing dispersed particles of organomodified MMT at 20 degrees C. Nanocomposite films were prepared from these solutions by solution casting and heated subsequently at a programmed heating rate. These films were transparent and brown in color. The extent of layer separation in nanocomposite films depends upon the chemical structure of the organoclay. These films were characterized by inherent viscosity, FT-IR, DSC, TMA, WAXD, TEM, UV, and TGA. The tensile behavior and surface energy studies were also investigated. The nanocomposite films had superior tensile properties, thermal behavior, and solvent resistance. Among the three organoclays, piperazine dihydrochloride was the best modifier. PMID:16108442

  3. Morpholylureas are a new class of potent and selective inhibitors of the type 5 17-?-hydroxysteroid dehydrogenase (AKR1C3).

    PubMed

    Flanagan, Jack U; Atwell, Graham J; Heinrich, Daniel M; Brooke, Darby G; Silva, Shevan; Rigoreau, Laurent J M; Trivier, Elisabeth; Turnbull, Andrew P; Raynham, Tony; Jamieson, Stephen M F; Denny, William A

    2014-02-01

    Inhibitors of the aldo-keto reductase enzyme AKR1C3 are of interest as potential drugs for leukemia and hormone-related cancers. A series of non-carboxylate morpholino(phenylpiperazin-1-yl)methanones were prepared by palladium-catalysed coupling of substituted phenyl or pyridyl bromides with the known morpholino(piperazin-1-yl)methanone, and shown to be potent (IC50?100nM) and very isoform-selective inhibitors of AKR1C3. Lipophilic electron-withdrawing substituents on the phenyl ring were positive for activity, as was an H-bond acceptor on the other terminal ring, and the ketone moiety (as a urea) was essential. These structure-activity relationships are consistent with an X-ray structure of a representative compound bound in the AKR1C3 active site, which showed H-bonding between the carbonyl oxygen of the drug and Tyr55 and His117 in the 'oxyanion hole' of the enzyme, with the piperazine bridging unit providing the correct twist to allow the terminal benzene ring to occupy the lipophilic pocket and align with Phe311. PMID:24411201

  4. Oxidation of cyclic dipeptides by photoinduced H-atom abstraction. A laser flash FT EPR and optical spectroscopy study.

    PubMed

    Tarábek, Peter; Bonifaci?, Marija; Beckert, Dieter

    2007-06-14

    Laser flash photolysis with the Fourier transform electron paramagnetic resonance (FT EPR) and optical spectroscopy detection methods on the nanosecond time scale have been employed in order to investigate the oxidation mechanism of cyclic dipeptides glycine, alanine, and sarcosine anhydrides initiated by SO4*- or 9,10-anthraquinone-2,6-disulfonate (2,6-AQDS) triplet in oxygen free aqueous solutions. A direct hydrogen abstraction from the ring C-H position of an anhydride by both oxidants is proposed as the primary reaction, rather then an electron transfer from nitrogen followed by (alpha)C-H deprotonation. The overall second-order rate constants for the reaction with SO4*- were determined to be 7.2 x 10(7) M(-1) s(-1), 1.2 x 10(8) M(-1) s(-1), and 5.2 x 10(8) M(-1) s(-1) for glycine anhydride, alanine anhydride, and sarcosine anhydride, respectively. The rate constants for 2,6-AQDS triplet as oxidizing species are about two times lower. The radical intermediate products derived from cyclic dipeptides observed on the microsecond time scale were assigned to the general structure of piperazine-2,5-dione-3-yl radical. These are spin polarized by the mechanisms of chemically induced dynamic electron polarization (CIDEP). For SO4*- as the oxidant the spectra are exhibiting an E/A* polarization pattern originating partially from F-pairs of two piperazine-2,5-dione-3-yl radicals. PMID:17516635

  5. Synthesis and in vitro pharmacological evaluation of indolyl carboxylic amide analogues as D3 dopamine receptor selective ligands.

    PubMed

    Tu, Zhude; Li, Shihong; Li, Aixiao; Taylor, Michelle; Ho, David; Malik, Maninder; Luedtke, Robert R; Mach, Robert H

    2013-09-01

    A series of substituted 1H-indolyl carboxylic acid amides that contain a N-(2-methoxyphenyl)piperazine or N-(2-fluoroethoxy)piperazine group were synthesized and their affinities for human dopamine D2, D3, and D4 receptors were determined. Two of these compounds, 14a and 14b, displayed high binding affinity at D3 (K i = 0.18 and 0.4 nM, respectively), and selectivity for D3 vs. D2 receptors (87-fold and 60-fold, respectively). These two compounds had low binding affinity at D4 receptors and ? receptor sites. The intrinsic activity of these compounds at D2 and D3 receptors was determined using a forskolin-dependent adenylyl cyclase inhibition assay; both 14a and 14b were found to be partial agonists. Furthermore, for compound 14a, the log D value of 2.85 suggested it has suitable lipophilicity for crossing the blood-brain-barrier. PMID:24156012

  6. Four trifluoromethylnitrobenzene analogues.

    PubMed

    Lynch, Daniel E; McClenaghan, Ian

    2004-01-01

    The crystal structures of four trifluoromethylnitrobenzene analogues (CF(3))C(6)H(3)(NO(2))[C(4)H(8)N(2)]R (where C(4)H(8)N(2) is piperazinyl and R is ethyl carboxylate, CO(2)C(2)H(5), or phenyl, C(6)H(5)), have been determined, and their conformations and packing arrangements are compared. The four compounds are ethyl 4-[4-nitro-2-(trifluoromethyl)phenyl]piperazine-1-carboxylate, (I), and ethyl 4-[2-nitro-4-(trifluoromethyl)phenyl]piperazine-1-carboxylate, (II), both C(14)H(16)F(3)N(3)O(4), and 1-[4-nitro-2-(trifluoromethyl)phenyl]-4-phenylpiperazine, (III), and 1-[2-nitro-4-(trifluoromethyl)phenyl]-4-phenylpiperazine, (IV), both C(17)H(16)F(3)N(3)O(2). All molecules adopt a rod-like conformation, while the asymmetric units of (II) and (IV) contain two unique molecules that pack as monodirectional pairs. All molecules pack with C-H...O/F close contacts to all but one of the O atoms and to five of the 18 F atoms. PMID:14712031

  7. Cr(III), Fe(III) and Co(III) complexes of tetradentate (ONNO) Schiff base ligands: Synthesis, characterization, properties and biological activity

    NASA Astrophysics Data System (ADS)

    Keskio?lu, Eren; Gündüzalp, Ayla Balaban; Çete, Servet; Hamurcu, Fatma; Erk, Birgül

    2008-08-01

    A series of metal complexes were synthesized from equimolar amounts of Schiff bases: 1,4-bis[3-(2-hydroxy-1-naphthaldimine)propyl]piperazine (bappnaf) and 1,8-bis[3-(2-hydroxy-1-naphthaldimine)- p-menthane (damnaf) with metal chlorides. All of synthesized compounds were characterized by elemental analyses, spectral (UV-vis, IR, 1H- 13C NMR, LC-MS) and thermal (TGA-DTA) methods, magnetic and conductance measurements. Schiff base complexes supposed in tetragonal geometry have the general formula [M(bappnaf or damnaf)]Cl· nH 2O, where M = Cr(III), Co(III) and n = 2, 3. But also Fe(III) complexes have octahedral geometry by the coordination of two water molecules and the formula is [Fe(bappnaf or damnaf)(H 2O) 2]Cl. The changes in the selected vibration bands in FT-IR indicate that Schiff bases behave as (ONNO) tetradentate ligands and coordinate to metal ions from two phenolic oxygen atoms and two azomethine nitrogen atoms. Conductance measurements suggest 1:1 electrolytic nature of the metal complexes. The synthesized compounds except bappnaf ligand have the antimicrobial activity against the bacteria: Escherichia coli (ATCC 11230), Yersinia enterocolitica (ATCC 1501), Bacillus magaterium (RSKK 5117), Bacillus subtilis (RSKK 244), Bacillus cereus (RSKK 863) and the fungi: Candida albicans (ATCC 10239). These results have been considerably interest in piperazine derivatives due to their significant applications in antimicrobial studies.

  8. Synthesis and preliminary pharmacological evaluation of imidazo[2,1- f]purine-2,4-dione derivatives

    Microsoft Academic Search

    Agnieszka Zagórska; S?awomir Jurczyk; Maciej Paw?owski; Ma?gorzata Dyba?a; Gabriel Nowak; Ewa Tatarczy?ska; Agnieszka Nikiforuk; Ewa Chojnacka-Wójcik

    2009-01-01

    A series of N-8-arylpiperazinylpropyl derivatives of 1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione (2–10) and amide derivatives of 1,3-dimethyl-6,7-dihydroimidazo[2,1-f]purine-2,4-(1H,3H)-dione-7-carboxylic acid (11–13) were synthesized. Compounds (2–10) evaluated in vitro were potent 5-HT1A receptor ligands. Preclinical studies indicated that 8-[3-(N4-phenyl)-piperazin-N1-yl-propyl]-1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione (2) exerts anxiolytic-like activity in the four-plate test in mice; however its effect was weaker, than that produced by Diazepam. This compound and 8-[3-(N4-2?-metoxyphenyl)-piperazin-N1-yl-propyl]-1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione (3) behaved like antidepressants

  9. Synthesis of mononuclear copper(II) complexes of acyclic Schiff's base ligands: spectral, structural, electrochemical, antibacterial, DNA binding and cleavage activity.

    PubMed

    Jayamani, Arumugam; Thamilarasan, Vijayan; Sengottuvelan, Nallathambi; Manisankar, Paramasivam; Kang, Sung Kwon; Kim, Young-Inn; Ganesan, Vengatesan

    2014-03-25

    The mononuclear copper(II) complexes (1&2) of ligands L(1) [N,N'-bis(2-hydroxy-5-methylbenzyl)-1,4-bis(3-iminopropyl)piperazine] or L(2) [N,N'-bis(2-hydroxy-5-bromobenzyl)-1,4-bis(3-iminopropyl) piperazine] have been synthesized and characterised. The single crystal X-ray study had shown that ligands L(1) and L(2) crystallize in a monoclinic crystal system with P21/c space group. The mononuclear copper(II) complexes show one quasireversible cyclic voltammetric response near cathodic region (-0.77 to -0.85 V) in DMF assignable to the Cu(II)/Cu(I) couple. Binding interaction of the complexes with calf thymus DNA (CT DNA) investigated by absorption studies and fluorescence spectral studies show good binding affinity to CT DNA, which imply both the copper(II) complexes can strongly interact with DNA efficiently. The copper(II) complexes showed efficient oxidative cleavage of plasmid pBR322 DNA in the presence of 3-mercaptopropionic acid as reducing agent through a mechanistic pathway involving formation of singlet oxygen as the reactive species. The Schiff bases and their Cu(II) complexes have been screened for antibacterial activities which indicates that the complexes exhibited higher antimicrobial activity than the free ligands. PMID:24317263

  10. Synthesis of mononuclear copper(II) complexes of acyclic Schiff's base ligands: Spectral, structural, electrochemical, antibacterial, DNA binding and cleavage activity

    NASA Astrophysics Data System (ADS)

    Jayamani, Arumugam; Thamilarasan, Vijayan; Sengottuvelan, Nallathambi; Manisankar, Paramasivam; Kang, Sung Kwon; Kim, Young-Inn; Ganesan, Vengatesan

    2014-03-01

    The mononuclear copper(II) complexes (1&2) of ligands L1 [N,N";-bis(2-hydroxy-5-methylbenzyl)-1,4-bis(3-iminopropyl)piperazine] or L2 [N,N";-bis(2-hydroxy-5-bromobenzyl)-1,4-bis(3-iminopropyl) piperazine] have been synthesized and characterised. The single crystal X-ray study had shown that ligands L1 and L2 crystallize in a monoclinic crystal system with P21/c space group. The mononuclear copper(II) complexes show one quasireversible cyclic voltammetric response near cathodic region (-0.77 to -0.85 V) in DMF assignable to the Cu(II)/Cu(I) couple. Binding interaction of the complexes with calf thymus DNA (CT DNA) investigated by absorption studies and fluorescence spectral studies show good binding affinity to CT DNA, which imply both the copper(II) complexes can strongly interact with DNA efficiently. The copper(II) complexes showed efficient oxidative cleavage of plasmid pBR322 DNA in the presence of 3-mercaptopropionic acid as reducing agent through a mechanistic pathway involving formation of singlet oxygen as the reactive species. The Schiff bases and their Cu(II) complexes have been screened for antibacterial activities which indicates that the complexes exhibited higher antimicrobial activity than the free ligands.

  11. Hybrid Membrane/Absorption Process for Post-combustion CO2 Capture

    SciTech Connect

    Li, Shiguang; Shou, S.; Pyrzynski, Travis; Makkuni, Ajay; Meyer, Howard

    2013-12-31

    This report summarizes scientific/technical progress made for bench-scale membrane contactor technology for post-combustion CO2 capture from DOE Contract No. DE-FE-0004787. Budget Period 1 (BP1) membrane absorber, Budget Period 2 (BP2) membrane desorber and Budget Period 3 (BP3) integrated system and field testing studies have been completed successfully and met or exceeded the technical targets (? 90% CO2 removal and CO2 purity of 97% in one membrane stage). Significant breakthroughs are summarized below: BP1 research: The feasibility of utilizing the poly (ether ether ketone), PEEK, based hollow fiber contractor (HFC) in combination with chemical solvents to separate and capture at least 90% of the CO2 from simulated flue gases has been successfully established. Excellent progress has been made as we have achieved the BP1 goal: ? 1,000 membrane intrinsic CO2 permeance, ? 90% CO2 removal in one stage, ? 2 psi gas side pressure drop, and ? 1 (sec)-1 mass transfer coefficient. Initial test results also show that the CO2 capture performance, using activated Methyl Diethanol Amine (aMDEA) solvent, was not affected by flue gas contaminants O2 (~3%), NO2 (66 ppmv), and SO2 (145 ppmv). BP2 research: The feasibility of utilizing the PEEK HFC for CO2-loaded solvent regeneration has been successfully established High CO2 stripping flux, one order of magnitude higher than CO2 absorption flux, have been achieved. Refined economic evaluation based on BP1 membrane absorber and BP2 membrane desorber laboratory test data indicate that the CO2 capture costs are 36% lower than DOE’s benchmark amine absorption technology. BP3 research: A bench-scale system utilizing a membrane absorber and desorber was integrated into a continuous CO2 capture process using contactors containing 10 to 20 ft2 of membrane area. The integrated process operation was stable through a 100-hour laboratory test, utilizing a simulated flue gas stream. Greater than 90% CO2 capture combined with 97% CO2 product purity was achieved throughout the test. Membrane contactor modules have been scaled from bench scale 2-inch diameter by 12-inch long (20 ft2 membrane surface area) modules to 4-inch diameter by 60-inch long pilot scale modules (165 ft2 membrane surface area). Pilot scale modules were tested in an integrated absorption/regeneration system for CO2 capture field tests at a coal-fired power plant (Midwest Generation’s Will County Station located in Romeoville, IL). Absorption and regeneration contactors were constructed utilizing high performance super-hydrophobic, nano-porous PEEK membranes with CO2 gas permeance of 2,000 GPU and a 1,000 GPU, respectively. Field tests using aMDEA solvent achieved greater than 90% CO2 removal in a single stage. The absorption mass transfer coefficient was 1.2 (sec)-1, exceeding the initial target of 1.0 (sec)-1. This mass transfer coefficient is over one order of magnitude greater than that of conventional gas/liquid contacting equipment. The economic evaluation based on field tests data indicates that the CO2 capture cost associated with membrane contactor technology is $54.69 (Yr 2011$)/tonne of CO2 captured when using aMDEA as a solvent. It is projected that the DOE’s 2025 cost goal of $40 (Yr 2011$)/tonne of CO2 captured can be met by decreasing membrane module cost and by utilizing advanced CO2 capture solvents. In the second stage of the field test, an advanced solvent, Hitachi’s H3-1 was utilized. The use of H3-1 solvent increased mass transfer coefficient by 17% as compared to aMDEA solvent. The high mass transfer coefficient of H3-1 solvent combined with much more favorable solvent regeneration requirements, indicate that the projected savings achievable with membrane contactor process can be further improved. H3-1 solvent will be used in the next pilot-scale development phase. The integrated absorption/regeneration process design and high performance membrane contactors developed in the current bench-scale program will be used as the base technology for future pilot-scale development.

  12. Automated determination of 'Ecstasy' and amphetamines in urine by SPME and capillary gas chromatography after propylchloroformate derivatisation.

    PubMed

    Ugland, H G; Krogh, M; Rasmussen, K E

    1999-03-01

    The determination of amphetamines and their methylenedioxylated analogs in urine by propylchloroformate derivatisation and automated solid-phase microextraction is described. The urine sample was adjusted to pH 10.8 and added propylchloroformate reagent and an internal standard. Derivatisation resulted in water-stable carbamates which were automatically extracted by solid-phase microextraction. A fiber coated with polydimethylsiloxane was inserted into the urine matrix and agitated for 16 min. The fibre with the extracted carbamates was injected into the heated split-splitless injection port of the gas chromatograph where the analytes were evaporated at 300 degrees C, separated on a methylsilicone capillary column and detected by either a nitrogen phosphorous detector or by mass spectrometry. The method was shown to be highly reproducible and robust with respect to variations in the urine matrices. The detection limits were 5 ng/ml(-1) of methamphetamine, MDMA and MDEA and 15 ng/ml(-1) of amphetamine and MDA in urine. The method is a solvent free, automated alternative to traditional methods for determination of the amphetamine and their methylendioxylated analogs in urine. PMID:10704112

  13. Solubility of nitrous oxide in alkanolamine aqueous solutions

    SciTech Connect

    Tsai, T.C.; Ko, J.J.; Wang, H.M.; Lin, C.Y.; Li, M.H.

    2000-04-01

    The solubility of nitrous oxide (N{sub 2}O) in alkanolamine aqueous solutions has been measured at (30, 35, and 40) C. The systems studied are monoethanolamine, diethanolamine, diisopropanolamine, triethanolamine, and 2-amino-2-methyl-1-propanol aqueous solutions. The concentration of amine for monoethanolamine ranges from (1 to 6) kmol/m{sup 3} and for other amines from (0.5 to 3) kmol/m{sup 3}. The accuracy of the measurement is estimated to be {+-}2%. A semiempirical model of the excess Henry's constant proposed by Wang et al. (1992) was used to correlate the solubility of N{sub 2}O in amine solutions. The parameters of the correlation were determined from the measured solubility data and the available data in the open literature. For a wide temperature range from (15 to 75) C, the obtained correlation has been shown to represent reasonably the solubility of N{sub 2}O in six amine aqueous solutions: MEA, DEA, DIPA, TEA, MDEA, and AMP. For the purpose of process design, the obtained correlations are, in general, satisfactory for estimating the solubility of N{sub 2}O in amine solutions, which in turn can be used to estimate the correct free-gas solubility of CO{sub 2} in amines.

  14. Accurate prediction of physical properties for acid gas treating

    SciTech Connect

    Lee, L.L. [Univ. of Oklahoma, Norman, OK (United States)

    1996-12-31

    A comprehensive, accurate, consistent, and dependable correlation is developed for modeling the thermodynamic properties of aqueous alkanolamine solutions used in the chemical treating of acid gases. The method is applicable to vapor-liquid equilibrium, heat of absorption (for both absorption and regeneration conditions), speciation, and hydrocarbon solubility calculations. Because it is based on valid physical principles and tested against benchmark data, the correlation is accurate for low loading and high loading conditions. The work covers the amines MDEA, DEA, MEA, and their blends from 20 C to 120 C (68 F--248 F) and for loadings of CO{sub 2}/H{sub 2}S from 0.001 to 1.6 (pressures from 0.002 to 10,800 kPa, or 0.0003 to 1,560 psia). The thermodynamic frame is based on a molecular electrolyte theory combined with a group contribution method. Special attention is paid to low loading pinch point operation and energy requirement calculations where industrial needs are focused.

  15. The on-line removal of non-regenerable salts from amine solutions using the UCARSEP{reg_sign} Process

    SciTech Connect

    Burns, D. [Union Carbide Corp., Houston, TX (United States); Gregory, R.A. [Union Carbide Corp., Bound Brook, NJ (United States)

    1995-11-01

    Amine unit contamination with non-regenerable salts, whether as a result of acid or inorganic salt incursion, or solvent degradation, is a common industry problem. In MEA systems this is usually addressed by the use of a reclaimer but this is not a practical solution for DEA, MDEA or formulated solvents. Similarly, the old approach of purging solvent is no longer economically or environmentally justifiable. Neutralization of amine salts with a strong base can significantly prolong the useful life of the amine solution but eventually some of the salt may have to be removed, especially if mechanical losses are low. Electrodialysis (ED) has recently been applied to this problem and has been found to overcome many of the disadvantages of vacuum distillation and ion exchange technologies, both of which have been used in recent years for solvent clean-up. Union Carbide adapted ED technology to the unique conditions encountered in an amine system and developed the UCARSEP{reg_sign} Process. A mobile UCARSEP{reg_sign} unit has been built to achieve on-line salt removal rates of 40 lbmol/day (about 3,300 lb/day). This has been successfully used to clean up UCARSOL{reg_sign} solvents as well as DEA. Case studies are presented and the relative merits of this and other clean-up options are discussed.

  16. Nitrile-functionalized tertiary amines as highly efficient and reversible SO2 absorbents.

    PubMed

    Hong, Sung Yun; Kim, Heehwan; Kim, Young Jin; Jeong, Junkyo; Cheong, Minserk; Lee, Hyunjoo; Kim, Hoon Sik; Lee, Je Seung

    2014-01-15

    Three different types of nitrile-functionalized amines, including 3-(N,N-diethylamino)propionitrile (DEAPN), 3-(N,N-dibutylamino)propionitrile (DBAPN), and N-methyl-N,N-dipropionitrile amine (MADPN) were synthesized, and their SO2 absorption performances were evaluated and compared with those of hydroxy-functionalized amines such as N,N-diethyl-N-ethanol amine (DEEA), N,N-dibutyl-N-ethanol amine (DBEA), and N-methyl-N,N-diethanol amine (MDEA). Absorption-desorption cycle experiments clearly demonstrate that the nitrile-functionalized amines are more efficient than the hydroxy-functionalized amines in terms of absorption rate and regenerability. Computational calculations with DBEA and DBAPN revealed that DBEA bearing a hydroxyethyl group chemically interacts with SO2 through oxygen atom, forming an ionic compound with a covalently bound OSO2(-) group. On the contrary, DBAPN bearing a nitrile group physically interacts with SO2 through the nitrogen and the hydrogen atoms of the two methylene groups adjacent to the amino and nitrile functionalities. PMID:24291666

  17. Frequency of biocide-resistant genes and susceptibility to chlorhexidine in high-level mupirocin-resistant, methicillin-resistant Staphylococcus aureus (MuH MRSA).

    PubMed

    Liu, Qingzhong; Zhao, Huanqiang; Han, Lizhong; Shu, Wen; Wu, Qiong; Ni, Yuxing

    2015-08-01

    The aim of this study was to determine the prevalence of biocide-resistant determinants and the susceptibility to chlorhexidine in high-level mupirocin-resistant, methicillin-resistant Staphylococcus aureus (MuH MRSA). Fifty-three MuH MRSA isolates were analyzed for plasmid-borne genes (qacA/B, smr, qacG, qacH, and qacJ) by polymerase chain reaction (PCR); for chromosome-mediated genes (norA, norB, norC, mepA, mdeA, sepA, and sdrM) by PCR and quantitative reverse transcription-PCR (qRT-PCR); and for susceptibility to chlorhexidine by MIC and minimum bactericidal concentration (MBC). Furthermore, disinfectant efficacy was tested in the presence of 3.0% bovine serum albumin (BSA) in MBC detection. The plasmid-borne genes qacA/B (83.0%) and smr (77.4%) and overexpressions of chromosome-mediated genes norA (49.0%) and norB (28.8%) were predominantly found in isolates studied, and 90.6% of the isolates revealed tolerance to chlorhexidine. In the presence of BSA, the average MBC of chlorhexidine for these isolates rose to 256?g/mL. Altogether, our results suggest that surveillance of sensitivity to biocides among MuH MRSA isolates is essential for hospital infection control. PMID:26008124

  18. Stereoisomeric profiling of drugs of abuse and pharmaceuticals in wastewaters of Valencia (Spain).

    PubMed

    Vazquez-Roig, Pablo; Kasprzyk-Hordern, Barbara; Blasco, Cristina; Picó, Yolanda

    2014-10-01

    The enantiomeric and diastereomeric profiling of chiral pharmaceuticals (ephedrine, norephedrine, atenolol and venlafaxine) and illicit drugs (amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA)) was undertaken over a period of fourteen consecutive days in three wastewater treatment plants (WWTPs) in the city of Valencia, Spain. Degradation efficiency of WWTPs was found to be compound and enantiomer dependent. Selective enantiomer enrichment was observed for several target analytes. Amphetamine and MDMA were enriched with R(-)-enantiomers. 1S,2S(+)-pseudoephedrine was found to be more readily degradable during activated sludge treatment than its diastereomer 1R,2S(-)-ephedrine. Atenolol underwent enrichment with either S(-)- or R(+)-enantiomer in different WWTPs. This unexpected enantiomeric variation in the stereoselective degradation of atenolol could be attributed to different processes utilized during activated sludge treatment. The application of (enantiomeric) profiling of wastewater revealed usage patterns of chiral drugs in the Valencia region. PMID:25029504

  19. Imatinib mesylate.

    PubMed

    Al-Hadiya, Badraddin M H; Bakheit, Ahmed H H; Abd-Elgalil, Ahmed A

    2014-01-01

    Imatinib (INN), marketed by Novartis as Gleevec (United States) or Glivec (Europe/Australia/Latin America), received Food & Drug Administration (FDA) approval in May 2001 and is a tyrosine kinase inhibitor used in the treatment of multiple cancers, most notably Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia. Like all tyrosine kinase inhibitors, imatinib works by preventing a tyrosine kinase enzyme. Because the BCR-Abl tyrosine kinase enzyme exists only in cancer cells and not in healthy cells, imatinib works as a form of targeted therapy-only cancer cells are killed through the drug's action. In this regard, imatinib was one of the first cancer therapies to show the potential for such targeted action and is often cited as a paradigm for research in cancer therapeutics. This study presents a comprehensive profile of imatinib, including detailed nomenclature, formulae, physico-chemical properties, methods of preparation, and methods of analysis (including compendial, electrochemical, spectroscopic, and chromatographic methods of analysis). Spectroscopic and spectrometric analyses include UV/vis spectroscopy, vibrational spectroscopy, nuclear magnetic resonance spectrometry ((1)H and (13)C NMR), and mass spectrometry. Chromatographic methods of analyses include electrophoresis, thin layer chromatography, and high-performance liquid chromatography. Preliminary stability investigations for imatinib have established the main degradation pathways, for example, oxidation to N-oxide under oxidative stress conditions. Stability was also carried out for the formulation by exposing to different temperatures 0°C, ambient temperature, and 40°C. No remarkable change was found in the drug content of formulation. This indicates that the drug was stable at the above optimized formulation. Stability studies under acidic and alkaline conditions have established the following main degradation products: ?-(4-Methyl-1-piperazinyl)-3'-{[4-(3-pyridyl)-2-pyrimidinyl] amino}-p-tolu-p-toluid-ide methanesulfonate and 4-(4-methylpiperazin-1-ylmethyl)-benzoic acid. The main degradation products under oxidation conditions, that is, 4-[(4-methyl-4-oxido-piperazin-1-yl)-methyl]-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-enzamide, 4-[(4-methyl-1-oxido-piperazin-1-yl)-methyl]-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide, and 4-[(4-methyl-1,4-dioxido-piperazin-1-yl)-methyl]-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-enzamide. Clinical application studies for pharmacodynamics, pharmacokinetics, mechanism of action, and clinical uses of the drug were also presented. Each of the above stages includes appropriate figures and tables. More than 50 references were given as proof of the above-mentioned studies. PMID:24794909

  20. The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain.

    PubMed

    Nagai, Fumiko; Nonaka, Ryouichi; Satoh Hisashi Kamimura, Kanako

    2007-03-22

    We developed a reproducible, simple, and small-scale method for determining the re-uptake and release of monoamines (dopamine, serotonin (5-HT) and norepinephrine) using rat brain synaptosomes. These assays were then applied to study the effects of different kinds of non-medically used psychoactive drugs on monoamine re-uptake and release. The phenethylamine derivatives, 4-fluoroamphetamine, 2-methylamino-3,4-methylene-dioxy-propiophenone (methylone), 1-(1,3-benzodioxol-5-yl)-2-butanamine (BDB), and N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), had strong inhibitory effects on the re-uptake of dopamine, 5-HT and norepinephrine. 4-Fluoroamphetamine, methylone and BDB also strongly increased the release of the three monoamines, but MBDB increased 5-HT and norepinephrine release, but had little effect on dopamine release. However, 2,5-dimethoxy-4-iodophenethylamine (2C-I), 2,5-dimethoxy-4-ethylphenethylamine (2C-E), 2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,4,5-trimethoxyamphetamine (TMA-2) and 2,4,6-trimethoxyamphetamine (TMA-6), which are methoxylated phenethylamine derivatives, slightly influenced the re-uptake and release of monoamines. Alpha-metyltryptamine (AMT), a tryptamine derivative, was one of the strongest re-uptake inhibitors and releasers of the three monoamines. The tryptamine derivative, 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), also strongly inhibited re-uptake and increased the release of the three monoamines. N,N-dipropyltryptamine (DPT), 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), 5-methoxy-N,N-methylisopropyltryptamine (5-MeO-MIPT), and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) inhibited monoamine re-uptake, but had a few effects on monoamine release. 1-(3-Chlorophenyl)piperazine (3CPP) and 1-(methoxyphenyl)piperazine (4MPP), which are piperazine derivatives, inhibited monoamine re-uptake and accelerated their release. The results suggest that some designer drugs strongly act on the central nerve system to the same extent as restricted drugs. PMID:17223101

  1. High throughput screening of CO2 solubility in aqueous monoamine solutions.

    PubMed

    Porcheron, Fabien; Gibert, Alexandre; Mougin, Pascal; Wender, Aurélie

    2011-03-15

    Post-combustion Carbon Capture and Storage technology (CCS) is viewed as an efficient solution to reduce CO(2) emissions of coal-fired power stations. In CCS, an aqueous amine solution is commonly used as a solvent to selectively capture CO(2) from the flue gas. However, this process generates additional costs, mostly from the reboiler heat duty required to release the carbon dioxide from the loaded solvent solution. In this work, we present thermodynamic results of CO(2) solubility in aqueous amine solutions from a 6-reactor High Throughput Screening (HTS) experimental device. This device is fully automated and designed to perform sequential injections of CO(2) within stirred-cell reactors containing the solvent solutions. The gas pressure within each reactor is monitored as a function of time, and the resulting transient pressure curves are transformed into CO(2) absorption isotherms. Solubility measurements are first performed on monoethanolamine, diethanolamine, and methyldiethanolamine aqueous solutions at T = 313.15 K. Experimental results are compared with existing data in the literature to validate the HTS device. In addition, a comprehensive thermodynamic model is used to represent CO(2) solubility variations in different classes of amine structures upon a wide range of thermodynamic conditions. This model is used to fit the experimental data and to calculate the cyclic capacity, which is a key parameter for CO(2) process design. Solubility measurements are then performed on a set of 50 monoamines and cyclic capacities are extracted using the thermodynamic model, to asses the potential of these molecules for CO(2) capture. PMID:21341690

  2. CO2 Capture by Absorption with Potassium Carbonate

    SciTech Connect

    Gary T. Rochelle; Marcus Hilliard; Eric Chen; Babatunde Oyenekan; Ross Dugas; John McLees; Andrew Sexton; Daniel Ellenberger

    2005-10-26

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. Modeling of stripper performance suggests that vacuum stripping may be an attractive configuration for all solvents. Flexipac 1Y structured packing performs in the absorber as expected. It provides twice as much mass transfer area as IMTP No.40 dumped packing. Independent measurements of CO{sub 2} solubility give a CO{sub 2} loading that is 20% lower than that Cullinane's values with 3.6 m PZ at 100-120 C. The effective mass transfer coefficient (K{sub G}) in the absorber with 5 m K/2.5 m PZ appears to be 0 to 30% greater than that of 30 wt% MEA.

  3. Investigation of the inhibiting action of O-, S- and N-dithiocarbamato(1,4,8,11-tetraazacyclotetradecane)cobalt(III) complexes on the corrosion of iron in HClO 4 acid

    NASA Astrophysics Data System (ADS)

    Babi?-Samardžija, K.; Khaled, K. F.; Hackerman, N.

    2005-02-01

    The inhibiting properties of four macrocyclic cobalt(III) complexes of the general formula [Co III(Rdtc)cyclam](ClO 4) 2, where cyclam and Rdtc- refer to 1,4,8,11-tetraazacyclotetradecane and morpholine-, thiomorpholine-, piperazine-, N-methylpiperazine-dithiocarbamates, respectively, has been studied on the corrosion of iron in aerated 0.1 M HClO 4 solutions by potentiodynamic polarization (dc) technique and electrochemical impedance spectroscopy (ac). Inhibitor efficiency for the corrosion of iron is found to be better for cobalt complexes then for related amino-ligands. The impedance increases with inhibitor concentration. Polarization curves indicate that the inhibitors are predominantly mixed-type. Better protection by the complex inhibitors was obtained with longer immersion time. The best fit for inhibitors adsorption is obtained using the Langmuir isotherm model. Molecular modeling calculations were used to correlate structural properties of the complex species and their inhibition efficiency.

  4. Synthesis, structure and luminescence behaviour of bis(tridentate) Schiff base bridged dinuclear lead(II) pseudohalides

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, Soumi; Bhar, Kishalay; Khan, Sumitava; Mitra, Partha; Butcher, Raymond J.; Ghosh, Barindra K.

    2010-03-01

    Two pentacoordinated dinuclear lead(II) compounds [Pb 2(pbap)(N 3) 4] ( 1) and [Pb 2(pbap)(NCS) 4] ( 2) [pbap = N-((1-pyridin-2-yl)benzylidene)- N'-[2-(4-{2-[((1-pyridin-2-yl)benylidene)amino]ethyl}piperazin-1-yl)ethyl]amine] are prepared and characterized using microanalytical, spectroscopic, thermal and other physicochemical results. Single crystal X-ray diffraction measurements have been made to define the metal coordination spheres. Structural analyses reveal dinucleating bis(tridentate) behaviour of the hexadentate Schiff base (pbap) binding two metal ions. In the centrosymmetric dimers 1 and 2, each lead(II) center adopts a distorted square pyramidal geometry with PbN 5 chromophore ligated by each (N p, N i, N a) donor set of pbap and two N atoms of terminal pseudohalides. In DMF solutions at room temperature the complexes display high-energy intraligand 1(?-??) fluorescence.

  5. CO2 CAPTURE BY ABSORPTION WITH POTASSIUM CARBONATE

    SciTech Connect

    Gary T. Rochelle; Marcus Hilliard; Eric Chen; Babatunde Oyenekan; Ross Dugas; John McLees

    2005-07-31

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. The baseline campaign with 30% MEA has given heat duties from 40 to 70 kcal/gmol CO{sub 2} as predicted by the stripper model. The Flexipak 1Y structured packing gives significantly better performance than IMTP 40 duped packing in the absorber, but in the stripper the performance of the two packings is indistinguishable. The FTIR analyzer measured MEA volatility in the absorber represented by an activity coefficient of 0.7. In the MEA campaign the material balance closed with an average error of 3.5% and the energy balance had an average error of 5.9.

  6. Crystallographic and magnetic properties of fine iron nitride powders prepared by solid state reactions between iron and organic H{sub x}(CN)-ring compounds

    SciTech Connect

    Kaczmarek, W.A. [Australian National Univ., Canberra (Australia). Research School of Physical Sciences and Engineering] [Australian National Univ., Canberra (Australia). Research School of Physical Sciences and Engineering

    1995-12-01

    In this work morphological, crystallographic and magnetic properties of iron nitride powders prepared by room temperature mechano-chemical processing, were studied by SEM, XRD and VSM methods. Nitridation reaction occurs during ball milling of a stoichiometric mixture of {alpha}Fe powder and highly reactive complex amine compounds: piperazine, pyrazine and pyrazole in the molar ratio 3:1 (Fe:N). The amount of nitride phase produced, depends on milling time, annealing temperature and on the chemical reactivity of the amine compound with iron. Calculation of crystal lattice parameters show that prepare nitrides are similar to stoichiometric Fe{sub 3}N hcp type structure. Lattice expansion was found for hexagonal planes due to increasing nitrogen concentration. Magnetic hysteresis parameters were found to be very sensitive to changes in chemical composition. As the amount of nitrogen increases magnetic remanence and coercivity increase but magnetization and calculated average magnetic moment per Fe atom decrease.

  7. Novel psychoactive substances of interest for psychiatry.

    PubMed

    Schifano, Fabrizio; Orsolini, Laura; Duccio Papanti, G; Corkery, John M

    2015-02-01

    Novel psychoactive substances include synthetic cannabinoids, cathinone derivatives, psychedelic phenethylamines, novel stimulants, synthetic opioids, tryptamine derivatives, phencyclidine-like dissociatives, piperazines, GABA-A/B receptor agonists, a range of prescribed medications, psychoactive plants/herbs, and a large series of performance and image enhancing drugs. Users are typically attracted by these substances due to their intense psychoactive effects and likely lack of detection in routine drug screenings. This paper aims at providing psychiatrists with updated knowledge of the clinical pharmacology and psychopathological consequences of the use of these substances. Indeed, these drugs act on a range of neurotransmitter pathways/receptors whose imbalance has been associated with psychopathological conditions, including dopamine, cannabinoid CB1, GABA-A/B, 5-HT2A, glutamate, and k opioid receptors. An overall approach in terms of clinical management is briefly discussed. PMID:25655145

  8. A divalent quaternary alkyl ammonium salt as the electrolyte for high-energy electric double-layer capacitors

    NASA Astrophysics Data System (ADS)

    Zheng, Cheng; Yoshio, Masaki; Qi, Li; Wang, Hongyu

    2012-12-01

    A divalent electrolyte salt based on 1,1,4,4-tetramethyl piperazine has been synthesized and applied in electric double-layer capacitors (EDLCs). Traits of the divalent salts have been accessed as well as monovalent quaternary alkyl ammonium salts by the means of galvanostatic charge-discharge tests and ionic conductivity measurements. Compared with monovalent salts, the divalent salts do enlarge the charge storage ability of EDLCs remarkably. However, highly concentrated charge density on the divalent cation has a strong interaction with the organic solvent of propylene carbonate. The adverse effect of this heavy solvation on the performance of EDLCs has been investigated. Moreover, the influence of pore size distribution on the storage ability of these cations at the porous carbon electrode has been addressed.

  9. Computational Insights into the Interactions between DNA and siRNA with “Rigid” and “Flexible” Triazine Dendrimers

    PubMed Central

    Pavan, Giovanni M.; Mintzer, Meredith A.; Simanek, Eric E.; Merkel, Olivia M.; Kissel, Thomas; Danani, Andrea

    2013-01-01

    In this study, simulation challenges intuitive models of “flexible” and “rigid” generation two triazine dendrimers as it pertains to solution conformation and conformation on binding DNA or siRNA sequences. These results derive from structural and energetic analyses of the binding events. Simulations of the rigid structure reinforce the role of the constrained piperazine linker in positioning the peripheral groups at significant distance from each other and the core of the dendrimer. In contrast, the flexible dendrimer, characterized by triethyleneglycol-like linkers, collapses in solution. On binding DNA and siRNA, these conformations are largely retained. The rigid dendrimer undergoes reorganization of peripheral groups to generate a large number of contacts to the nucleic acid. In contrast, the flexible dendrimer, originally conceived to create multivalent interactions with nucleic acids, generates only a few contacts and collapses further. This paper provides unique insight in the role played by molecular flexibility in the binding phenomenon. PMID:20131771

  10. From AChE to BACE1 inhibitors: The role of the amine on the indanone scaffold.

    PubMed

    Rampa, Angela; Mancini, Francesca; De Simone, Angela; Falchi, Federico; Belluti, Federica; Di Martino, Rita Maria Concetta; Gobbi, Silvia; Andrisano, Vincenza; Tarozzi, Andrea; Bartolini, Manuela; Cavalli, Andrea; Bisi, Alessandra

    2015-07-15

    In recent years, a progressive increase in age-related disorders could be observed in most western countries, among which Alzheimer's disease (AD) is one of the most challenging. BACE1 could be seen as an attractive target to develop disease-modifying compounds, and in this context, a new series of hybrid molecules was designed and synthesized, based on a previously identified multitarget lead compound. In particular, the amino side chain was appropriately modified to fit BACE1 as additional target. In vitro testing results pointed out compound 8 (IC50=2.49±0.08?M), bearing the bulky bis(4-fluorophenyl)methyl)piperazine substituent, as the most potent BACE1 inhibitor of the series. PMID:26003339

  11. The O H···O, O H···N and C H···O hydrogen bonds in 1,4-dimethylpiperazine mono-betaine monohydrate

    NASA Astrophysics Data System (ADS)

    Dega-Szafran, Z.; Katrusiak, A.; Szafran, M.

    2008-05-01

    1,4-Dimethylpiperazine mono-betaine (1-carboxymethyl-1,4-dimethylpiperazinium inner salt, MBPZ) crystallizes as monohydrate. The crystals are orthorhombic, space group Pccn. Two MBPZ molecules and two water molecules form a cyclic oligomer, (MBPZ·H 2O) 2. The O-H···O and O-H···N hydrogen bonds are of 2.769(1) and 2.902(1) Å, respectively. The dimers interact with the neighboring molecules through the C-H···O hydrogen bonds of 3.234(1) Å. The piperazine ring assumes a chair conformation with the N(4)-CH 3 and N +(1)-CH 2COO - groups in the equatorial position and the N +(1)-CH 3 group in the axial one. The FTIR spectrum is compared with that calculated by the B3LYP/6-31G(d,p) level of theory.

  12. Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors

    PubMed Central

    Cuny, Gregory D.; Yu, Paul B.; Laha, Joydev K.; Xing, Xuechao; Liu, Ji-Feng; Lai, Carol S.; Deng, Donna Y.; Sachidanandan, Chetana; Bloch, Kenneth D.; Peterson, Randall T.

    2008-01-01

    A structure-activity relationship study of dorsomorphin, a previously identified inhibitor of SMAD 1/5/8 phosphorylation by bone morphogenetic protein (BMP) type 1 receptors ALK2, 3, and 6, revealed that increased inhibitory activity could be accomplished by replacing the pendent 4-pyridine ring with 4-quinoline. The activity contributions of various nitrogen atoms in the core pyrazolo[1,5-a]pyrimidine ring were also examined by preparing and evaluating pyrrolo[1,2-a]pyrimidine and pyrazolo[1,5-a]pyridine derivatives. In addition, increased mouse liver microsome stability was achieved by replacing the ether substituent on the pendent phenyl ring with piperazine. Finally, an optimized compound 13 (LDN-193189 or DM-3189) demonstrated moderate pharmacokinetic characteristics (e.g. plasma t1/2 = 1.6 h) following intraperitoneal administration in mice. These studies provide useful molecular probes for examining the in vivo pharmacology of BMP signaling inhibition. PMID:18621530

  13. General approach for electrochemical detection of persistent pharmaceutical micropollutants: Application to acetaminophen.

    PubMed

    Shi, S; Reisberg, S; Anquetin, G; Noël, V; Pham, M C; Piro, B

    2015-10-15

    We propose in this work a general and versatile methodology for electrochemical monitoring of persistent pharmaceutical micropollutants. The system presented is based on an electroactive and electropolymerized hapten (mimetic molecule of the pollutant to be detected) and a specific antibody that competitively binds either the hapten or the pollutant. The current delivered by the device depends on this competitive equilibrium and therefore on the pollutant?s concentration. The determination of the pharmaceutical product operates within minutes, using square wave voltammetry without labeling or addition of a reactant in solution; the competitive hapten/antibody transduction produces a "signal-on" (a current increase). Applied to acetaminophen, this electrochemical immunosensor presents a very low detection limit of ca. 10pM, (S/N=3) and a very high selectivity towards structural analogs (aspirin, BPA, and piperazine) even in a mixture. PMID:25982729

  14. Amphoteric, prevailingly cationic L-arginine polymers of poly(amidoamino acid) structure: synthesis, acid/base properties and preliminary cytocompatibility and cell-permeating characterizations.

    PubMed

    Ferruti, Paolo; Mauro, Nicolò; Falciola, Luigi; Pifferi, Valentina; Bartoli, Cristina; Gazzarri, Matteo; Chiellini, Federica; Ranucci, Elisabetta

    2014-03-01

    A linear amphoteric poly(amidoamino acid), L-ARGO7, is prepared by Michael-type polyaddition of L-arginine with N,N'-methylenebisacrylamide. Chain-extension of acrylamide end-capped L-ARGO7 oligomers with piperazine leads to high-molecular-weight copolymers in which L-arginine maintains its absolute configuration. Acid/base properties of L-ARGO7 polymers show isolectric points of ? 10 and positive net average charges per repeating unit at pH = 7.4 from 0.25 to 0.40. These arginine-rich synthetic polymers possibly share some of the unique biological properties of polyarginine cell-permeating peptides. In vitro tests with mouse embryo fibroblasts balb/3T3 clone A31 show that L-ARGO7 polymers are endowed with effective cell internalization ability combined with minimal cytotoxicity. PMID:24821667

  15. CO2 Capture by Absorption with Potassium Carbonate

    SciTech Connect

    Gary T. Rochelle; Marcus Hilliard; Eric Chen; Babatunde Oyenekan; Ross Dugas; John McLees; Andrew Sexton; Amorvadee Veawab

    2005-01-26

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. In Campaign 3 of the pilot plant, the overall mass transfer coefficient for the stripper with 7 m MEA decreased from 0.06 to 0.01 mol/(m{sup 3}.s.kPa) as the rich loading increased from 0.45 to 0.6 mol CO{sub 2}/mol MEA. Anion chromatography has demonstrated that nitrate and nitrite are major degradation products of MEA and PZ with pure oxygen. In measurements with the high temperature FTIR in 7 m MEA the MEA vapor pressure varied from 2 to 20 Pa at 35 to 70 C. In 2.5 m PZ the PZ vapor pressure varied from 0.2 to 1 Pa from 37 to 70 C.

  16. UV-triggered affinity capture identifies interactions between the Plasmodium falciparum multidrug resistance protein 1 (PfMDR1) and antimalarial agents in live parasitized cells.

    PubMed

    Brunner, Ralf; Ng, Caroline L; Aissaoui, Hamed; Akabas, Myles H; Boss, Christoph; Brun, Reto; Callaghan, Paul S; Corminboeuf, Olivier; Fidock, David A; Frame, Ithiel J; Heidmann, Bibia; Le Bihan, Amélie; Jenö, Paul; Mattheis, Corinna; Moes, Suzette; Müller, Ingrid B; Paguio, Michelle; Roepe, Paul D; Siegrist, Romain; Voss, Till; Welford, Richard W D; Wittlin, Sergio; Binkert, Christoph

    2013-08-01

    A representative of a new class of potent antimalarials with an unknown mode of action was recently described. To identify the molecular target of this class of antimalarials, we employed a photo-reactive affinity capture method to find parasite proteins specifically interacting with the capture compound in living parasitized cells. The capture reagent retained the antimalarial properties of the parent molecule (ACT-213615) and accumulated within parasites. We identified several proteins interacting with the capture compound and established a functional interaction between ACT-213615 and PfMDR1. We surmise that PfMDR1 may play a role in the antimalarial activity of the piperazine-containing compound ACT-213615. PMID:23754276

  17. UV-triggered Affinity Capture Identifies Interactions between the Plasmodium falciparum Multidrug Resistance Protein 1 (PfMDR1) and Antimalarial Agents in Live Parasitized Cells*

    PubMed Central

    Brunner, Ralf; Ng, Caroline L.; Aissaoui, Hamed; Akabas, Myles H.; Boss, Christoph; Brun, Reto; Callaghan, Paul S.; Corminboeuf, Olivier; Fidock, David A.; Frame, Ithiel J.; Heidmann, Bibia; Le Bihan, Amélie; Jenö, Paul; Mattheis, Corinna; Moes, Suzette; Müller, Ingrid B.; Paguio, Michelle; Roepe, Paul D.; Siegrist, Romain; Voss, Till; Welford, Richard W. D.; Wittlin, Sergio; Binkert, Christoph

    2013-01-01

    A representative of a new class of potent antimalarials with an unknown mode of action was recently described. To identify the molecular target of this class of antimalarials, we employed a photo-reactive affinity capture method to find parasite proteins specifically interacting with the capture compound in living parasitized cells. The capture reagent retained the antimalarial properties of the parent molecule (ACT-213615) and accumulated within parasites. We identified several proteins interacting with the capture compound and established a functional interaction between ACT-213615 and PfMDR1. We surmise that PfMDR1 may play a role in the antimalarial activity of the piperazine-containing compound ACT-213615. PMID:23754276

  18. Coumarin-based octopamine phototriggers and their effects on an insect octopamine receptor.

    PubMed

    Schaal, Janina; Dekowski, Brigitte; Wiesner, Burkhard; Eichhorst, Jenny; Marter, Kathrin; Vargas, Carolyn; Keller, Sandro; Eremina, Nadejda; Barth, Andreas; Baumann, Arnd; Eisenhardt, Dorothea; Hagen, Volker

    2012-07-01

    We have developed and characterized efficient caged compounds of the neurotransmitter octopamine. For derivatization, we introduced [6-bromo-8-(diethylaminomethyl)-7-hydroxycoumarin-4-yl]methoxycarbonyl (DBHCMOC) and {6-bromo-7-hydroxy-8-[(piperazin-1-yl)methyl]coumarin-4-yl}methoxycarbonyl (PBHCMOC) moieties as novel photo-removable protecting groups. The caged compounds were functionally inactive when applied to heterologously expressed octopamine receptors (AmOct?1R). Upon irradiation with UV-visible or IR light, bioactive octopamine was released and evoked Ca2+ signals in AmOct?1R-expressing cells. The pronounced water solubility of compounds 2-4 in particular holds great promise for these substances as excellent phototriggers of this important neurotransmitter. PMID:22674503

  19. Mutagenicity of urine from mice exposed orally to nitrite and various aminated antiparasitic drugs

    SciTech Connect

    Alba, M.A.; Aguirre, J.E.; Ramirez, J.; de Nava, C.C. (U.N.A.M. (Mexico))

    1989-01-01

    Mutagenic N-nitroso compound formation from the in vitro reaction of amebicides and anthelmintic drugs, which are pyrimidine derivatives or contain secondary aliphatic amines or heterocyclic nitrogens, has been previously described. Under similar conditions, antiparasitic drugs containing halogenated derivatives of tertiary amines or quaternary ammonium salts do not form mutagenic nitrosated compounds. In the present study the mutagenic activity of mouse urine was determined after oral administration of sodium nitrite and the two above-mentioned groups of drugs. Results show that the simultaneous administration of piperazine or chloroquine with sodium nitrite produced urinary mutagens that appeared conjugated as glucuronides, whereas pyrantel pamoate and dehydroemetine in the presence of nitrite caused only slightly mutagenic urine. No mutagenic activity was detected in the urine of mice to which halogenated derivatives of tertiary amines (iodochlorhydroxyquin) or quaternary ammonium salts (bephenium hydroxynaphthoate) were administered together with nitrite.

  20. Gallium fluoroarsenates.

    PubMed

    Marshall, Kayleigh L; Armstrong, Jennifer A; Weller, Mark T

    2015-07-01

    Six new phases in the gallium-fluoride-arsenate system have been synthesised hydrofluorothermally using a fluoride-rich medium and "HAsF6" (HF?:?AsF5) as a reactant. RbGaF3(H2AsO4), KGaF(H2AsO4) and [piperazine-H2]2[Ga2F8(HAsO4)]·H2O have one dimensional structures, [DABCO-H2]2[Ga4F7O2H(AsO4)2]·4H2O consists of two dimensionally connected polyhedral layers, while GaF(AsO3[OH,F])2 and (NH4)3Ga4F9(AsO4)2 both have three-dimensionally connected polyhedral frameworks. PMID:26095086

  1. Novel psychoactive substances of interest for psychiatry

    PubMed Central

    Schifano, Fabrizio; Orsolini, Laura; Duccio Papanti, G; Corkery, John M

    2015-01-01

    Novel psychoactive substances include synthetic cannabinoids, cathinone derivatives, psychedelic phenethylamines, novel stimulants, synthetic opioids, tryptamine derivatives, phencyclidine-like dissociatives, piperazines, GABA-A/B receptor agonists, a range of prescribed medications, psychoactive plants/herbs, and a large series of performance and image enhancing drugs. Users are typically attracted by these substances due to their intense psychoactive effects and likely lack of detection in routine drug screenings. This paper aims at providing psychiatrists with updated knowledge of the clinical pharmacology and psychopathological consequences of the use of these substances. Indeed, these drugs act on a range of neurotransmitter pathways/receptors whose imbalance has been associated with psychopathological conditions, including dopamine, cannabinoid CB1, GABA-A/B, 5-HT2A, glutamate, and k opioid receptors. An overall approach in terms of clinical management is briefly discussed. PMID:25655145

  2. Isolation and structural elucidation of a new sildenafil analogue from a functional coffee.

    PubMed

    Li, Lin; Low, Min-Yong; Ge, Xiaowei; Bloodworth, Bosco C; Koh, Hwee-Ling

    2013-05-01

    A sildenafil analogue was detected in a functional coffee sample labelled to have male sexual performance enhancement effects. This analogue was isolated and purified by flash chromatography and preparative high-performance liquid chromatography. Its structure was elucidated using high-resolution mass spectrometry; electrospray ionization-tandem mass spectrometry; and nuclear magnetic resonance spectroscopy, ultraviolet spectroscopy, and infrared spectroscopy. Compared with sildenafil, instead of an N-methylpiperazinyl moiety, ring opening of the piperazine ring with the loss of a carbon atom resulted in a substituted benzenesulfonamide. The chemical name of this analogue is N-[2-(dimethylamino)ethyl]-4-ethoxy-3-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide. It is named descarbonsildenafil because it has one less carbon atom when compared with sildenafil. PMID:22825675

  3. Discovery of a Potent Parenterally Administered Factor XIa Inhibitor with Hydroxyquinolin-2(1H)-one as the P2' Moiety.

    PubMed

    Hu, Zilun; Wong, Pancras C; Gilligan, Paul J; Han, Wei; Pabbisetty, Kumar B; Bozarth, Jeffrey M; Crain, Earl J; Harper, Timothy; Luettgen, Joseph M; Myers, Joseph E; Ramamurthy, Vidhyashankar; Rossi, Karen A; Sheriff, Steven; Watson, Carol A; Wei, Anzi; Zheng, Joanna J; Seiffert, Dietmar A; Wexler, Ruth R; Quan, Mimi L

    2015-05-14

    Structure-activity relationship optimization of phenylalanine P1' and P2' regions with a phenylimidazole core resulted in a series of potent FXIa inhibitors. Introducing 4-hydroxyquinolin-2-one as the P2' group enhanced FXIa affinity and metabolic stability. Incorporation of an N-methyl piperazine amide group to replace the phenylalanine improved both FXIa potency and aqueous solubility. Combination of the optimization led to the discovery of FXIa inhibitor 13 with a FXIa K i of 0.04 nM and an aPTT EC2x of 1.0 ?M. Dose-dependent efficacy (EC50 of 0.53 ?M) was achieved in the rabbit ECAT model with minimal bleeding time prolongation. PMID:26005539

  4. CO2 CAPTURE BY ABSORPTION WITH POTASSIUM CARBONATE

    SciTech Connect

    Gary T. Rochelle; Eric Chen; Jennifer Lu; Babatunde Oyenekan; Ross Dugas

    2005-04-29

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. Stripper modeling suggests the energy requirement with a simple stripper will be about the same for 5 m K{sup +}/2.5 m PZ and 7 m MEA. Modeling with a generic solvent shows that the optimum heat of CO{sub 2} desorption to minimize heat duty lies between 15 and 25 kcal/gmol. On-line pH and density measurements are effective indicators of loading and total alkalinity for the K+/PZ solvent. The baseline pilot plant campaign with 30% MEA has been started.

  5. Structure-activity studies on the protection of Trimetazidine derivatives modified with nitroxides and their precursors from myocardial ischemia-reperfusion injury.

    PubMed

    Kálai, Tamás; Khan, Mahmood; Balog, Mária; Kutala, Vijay Kumar; Kuppusamy, Periannan; Hideg, Kálmán

    2006-08-15

    Trimetazidine, the known anti-anginal and anti-ischemic drug, was modified by pyrroline and tetrahydropyridine nitroxides and their hydroxylamine and sterically hindered secondary amine precursors. The synthesized new compounds proved to be better superoxide scavenger molecules compared to the parent Trimetazidine in an in vitro experiment. This reactive oxygen species (ROS) scavenging activity was further supported by ischemia/reperfusion (I/R) studies on Langendorff-perfused rat hearts pretreated with Trimetazidine and with the modified Trimetazidine derivatives before ischemia. Two of the investigated compounds, containing 2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole and 4-phenyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole substituents on the piperazine ring, provided significant protection from the cardiac dysfunction caused by I/R. The protective effect could be attributed to the combined anti-ischemic and antioxidant effects. PMID:16697647

  6. [H 2(C 4H 10N 2)] 2(H 2PO 4) 4: hydrothermal synthesis and single crystal structure of an inclusive supramolecular phosphoric salt

    Microsoft Academic Search

    Fa-Nian Shi; Zhen Shen; Xiao-Zeng You; Chun-Ying Duan

    2000-01-01

    The new supramolecular phosphoric complex [H2(C4H10N2)]2(H2PO4)4 has been obtained by the hydrothermal reaction of piperazine hexahydrate (C4H10N2·6H2O), Zn(OAc)2 with H3PO4 in the molar ratio of 1:1:2 at 180°C. The compound was characterized by the means of elemental analysis, FT-IR, TGA-DTA, and single crystal X-ray analysis. The structure was determined with data: triclinic, space group P-1(no. 2), a=7.020(9)A?,b=7.694(2)A?,c=12.076(2)A?,?=84.41°, ?=81.51°, ?=62.92(2)°, V=574.04(2)A?3,

  7. NMR Investigation of the Copper(II)-Ciprofloxacin System

    PubMed Central

    Košmrlj, Janez; Andersen, Bjørn; Sletten, Einar

    1999-01-01

    A proton NMR study was performed on the copper(ll)-ciprofloxacin system. The proton relaxation times (T1) were determined from the titration data in acidic and basic media. In acidic medium the H5 signal is dramatically affected and it is assumed that copper is bonded to the quinolone through carbonyl and one of the carboxyl oxygens. Such bonding is in agreement with the X-ray literature data for the complex [Cu(cf)1]Cl2.6H2O isolated from the slightly acidic solution. There are additional significant changes in 1T1 of H3? and H5? atoms which suggest that the terminal nitrogen atom of the piperazine ring system-N4? also interacts with copper in the basic conditions. Thus it is plausible that more than one species are present in the solution at high pH values. PMID:18475873

  8. Pulse radiolysis study on electrons trapped in semiclathrates and non-clathrate hydrates

    SciTech Connect

    Zagorski, Z.P.

    1987-02-12

    Trapping of electrons in specific water molecule vacancies, observed previously in crystalline aqueous clathrates, has also been found in semiclathrates (e.g., tetramethylammonium hydroxide pentahydrate), in clathrates showing hydrogen bonds between host and guest molecules (e.g., piperazine clathrate), and also in inorganic hydrates (e.g., sodium carbonate decahydrate). The lifetime of the electron is sometimes longer than in the case of true clathrates; e.g., t/sub 1/2/ = 3.5 ms (first-order decay in piperazine clathrate). The existence of comparatively long-lived electrons at room temperature may be considered a general phenomenon. The condition for its occurrence is the presence of OH/sup -/ or F/sup -/ anion, which can substitute for H/sub 2/O in the aqueous part of the compound and when displaced leaves an electron trap. In other ionic and nonionic compounds, the condition for the trapping of long-lived electrons is protonation of the principal compound, thereby leaving the solution or melt alkaline during the crystallization of the hydrate. Interpretation in terms of preexistent traps invokes the crystal imperfections chemistry, which in the case of hydrates has not yet been noticed. It has been assumed that electrons occupy the vacancies temporarily revealing their presence. In some clathrates and other hydrates, the long-lived electron traps do not occur; instead, the electron shows a similar spectrum (620 nm maximum), decaying by 2-3 orders of magnitude faster than in long-lived traps. It is assumed that this is a case of electron digging its own hole, although an alternative explanation may be through trapping in other kinds of crystal imperfections in the aqueous moiety of the hydrate.

  9. Prevalence of new psychoactive substances: A retrospective study in hair.

    PubMed

    Rust, Kristina Yasmin; Baumgartner, Markus R; Dally, Annika M; Kraemer, Thomas

    2012-06-01

    New psychoactive substances are conquering the drug scene. Police seize different colourful packages with exceptional names. They are declared as 'bath salts', 'plant food', or 'research chemical powders'. Little is known about the actual prevalence of these drugs. Reanalysis of hair samples from routine cases concerning the presence of new psychoactive substances or 'smart drugs' should provide insight into changing patterns of designer drugs. All hair samples from 2009 and 2010 that originally tested positive for amphetamines or MDMA (N?=?325) were reanalyzed for new or smart drugs such as 4-fluoroamphetamine, piperazines (BZP, mCPP and TFMPP), cathinones (4-MMC (mephedrone), methylone, butylone, ethylone, MDPV, methcathinone and cathinone), methylphenidate and ketamine. Hair snippets were extracted using a two-step extraction procedure. The analytes were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) (electrospray ionization; multiple-reaction-monitoring mode - information dependent acquisition - enhanced product ion scan). New psychoactive substances were found in 120 cases (37%). Concerning the piperazine drugs, mCPP was positive in 34 (10.5%) cases and TFMPP in one case. Five mCPP cases were also positive for trazodone, an antidepressant which is metabolized to mCPP. In 11 (3%) cases, 4-MMC was detected. Concerning the smart drugs, methylphenidate was found in 16 (5%). Ketamine was found in 45 (14%) cases. 4-Fluoroamphetamine was identified in 12 (4%) cases and methylone in one case.In conclusion, there is a high prevalence of these drugs. Consequently, at least the most common ones (e.g. mCPP, KET, 4-MMC and 4-FA) should be included in screening procedures in clinical and forensic toxicology. PMID:22522922

  10. BIMT 17, a 5-HT2A receptor antagonist and 5-HT1A receptor full agonist in rat cerebral cortex.

    PubMed

    Borsini, F; Giraldo, E; Monferini, E; Antonini, G; Parenti, M; Bietti, G; Donetti, A

    1995-09-01

    In the search for antidepressant agents with a rapid onset of action, we have found that compound BIMT 17 (1-[2-[4-(3-trifluoromethylphenyl)piperazin-1- yl]ethyl]benzimidazol-[1H]-2-one) shows a good affinity for cerebral cortical 5-HT1A (pKi = 7.72) and 5-HT2A (pKi = 6.90) receptors, with no appreciable affinity for the other 5-HT receptor subtypes, including 5-HT2C. BIMT 17 reduced forskolin-stimulated cAMP accumulation in the cerebral cortex (pEC50 = 6.09) and in the hippocampus (pEC50 = 6.50), and antagonized 5-HT-induced phosphatidylinositol turnover (pKi = 6.96) in the cerebral cortex. The effect on cAMP accumulation was blocked by the 5-HT1A receptor antagonist tertatolol. Buspirone, 8-OH-DPAT and S 14671 (1-[2-(2-thenoylamino)ethyl]- 4[1-(7-methoxynaphtyl)]-piperazine), claimed to be 5-HT1A receptor agonists, did not reduce forskolin-stimulated cAMP formation in the cerebral cortex. On the basis of these data, it was concluded that BIMT 17 was the only compound that behaved as a full agonist with respect to the cAMP response in the cortex, while exerting concurrent agonism at 5-HT1A receptors and antagonism at 5-HT2A receptors. These characteristics might explain the peculiar behavior of BIMT 17 in mimicking the inhibitory action of 5-HT on the basal firing rate of the cortical neurons (see accompanying paper). PMID:8584042

  11. Synthesis and antibacterial activity of novel levofloxacin derivatives containing a substituted thienylethyl moiety

    PubMed Central

    2012-01-01

    Background and the purpose of the study Piperazinyl quinolones such as ciprofloxacin, ofloxacin and levofloxacin are an important group of quinolone antimicrobials which are widely used in the treatment of various infectious diseases. In the present study, we synthesized a new series of levofloxacin derivatives and evaluated their antibacterial activities. Methods The N-substituted analogs of levofloxacin 6a–j were prepared by nucleophilic reaction of N-desmethyl levofloxacin 11 with thienylethyl bromide derivatives 8 or 9. All target compounds were tested using conventional agar dilution method in comparison to levofloxacin and N-desmethyl levofloxacin and their MIC values were determined against a panel of Gram-positive and Gram-negative bacteria. Results All compounds showed significant antibacterial activities against Gram-positive bacteria (MIC?=?0.04-6.25 ?g/mL); however, the activity against Gram-negative bacteria was lower (MIC?=?1.56–100 ?g/mL). As is evident from the data, oxime derivatives 6e, 6h and 6i are superior in inhibiting the growth of Gram-positive bacteria (MIC?=?0.04–0.19 ?g/mL), and their activities were found to be 5–25 times better than N-desmethyl levofloxacin 11 and equal or better than levofloxacin 4. Conclusion We have designed and synthesized novel quinolone derivatives bearing functionalized thienylethyl moiety on the piperazine ring of levofloxacin. The results of antibacterial screening against Gram-positive and Gram-negative bacteria revealed that the introduction of functionalized thienylethyl moiety on the piperazine ring of levofloxacin can improve the activity against Gram-positive bacteria. Gram-positive bacteria are responsible for a wide range of infectious diseases, and rising resistance in this group is causing increasing concern. Thus, this study introduces structural features of levofloxacin scaffold for development of new candidates in the field of anti-Gram positive chemotherapy PMID:23351676

  12. Elucidation of structural relationships and assignment of /sup 1/H NMR spectra of transition-metal cyclidene complexes by 2-D NMR techniques

    SciTech Connect

    Meade, T.J.; Fendrick, C.A.; Padolik, P.A.; Cottrell, C.E.; Busch, D.H.

    1987-12-16

    The complete /sup 1/H NMR spectra of five nickel cyclidene macrocyclic complexes are assigned by using DEPT (distortionless enhancement by polarization transfer) and 2-D NMR techniques: /sup 1/H-/sup 13/C shift correlation, COSY (correlated shift), and NOESY (nuclear Overhauser enhanced correlated shift). The /sup 1/H NMR assignments are consistent with the complexes having an overall saddle shape with the two saturated six-membered rings (composed of nickel, two nitrogens, and a trimethylene chain) adopting a chair and a boat configuration similar to those observed in the X-ray crystal structures of these complexes. The /sup 1/H NMR spectra can distinguish between two possible configurations for the bridging moiety (lid-off and lid-on). The vinyl methyl groups, labeled as O and N, have a chemical shift separation greater the 0.35 ppm for a lid-off configuration and less than 0.15 ppm for a lid-on configuration. The complex (2,9,10,17,19,25,33,34-octamethyl-3,6,13,16,20,24,27,31-octaazapentacyclo(16.7.7.2/sup 8,11/.2/sup 3,6/.2/sup 13,16/)- octatriaconta-1,8,10,17,19,24,26,31,33-nonaene-K/sup 4/N)nickel(II) hexafluorophosphate (V) has a bridge that consists of durene(tetramethylbenzene) supported by two piperazine rings. Those protons on the piperazine rings that are in close proximity to the arene ring are shifted upfield due to shielding contributions of the ring currents. 23 references, 9 figures, 1 table.

  13. Metabolism of prazosin in rat, dog, and human liver microsomes and cryopreserved rat and human hepatocytes and characterization of metabolites by liquid chromatography/tandem mass spectrometry.

    PubMed

    Erve, John C L; Vashishtha, Sarvesh C; DeMaio, William; Talaat, Rasmy E

    2007-06-01

    Prazosin (2-[4-(2-furanoyl)-piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline) is an antihypertensive agent that was introduced to the market in 1976. It has since established an excellent safety record. However, in vitro metabolism of prazosin has not been investigated. This study describes the in vitro biotransformation of prazosin in liver microsomes from rats, dogs, and humans, as well as rat and human cryopreserved hepatocytes and characterization of metabolites using liquid chromatography/tandem mass spectrometry. The major in vivo biotransformation pathways reported previously in rats and dogs include demethylation, amide hydrolysis, and O-glucuronidation. These metabolic pathways were also confirmed in our study. In addition, several new metabolites were characterized, including a stable carbinolamine, an iminium species, and an enamine-all formed via oxidation of the piperazine ring. Two ring-opened metabolites generated following oxidative cleavage of the furan ring were also identified. Using semicarbazide hydrochloride as a trapping agent, an intermediate arising from opening of the furan ring was captured as a pyridazine product. In the presence of glutathione, three glutathione conjugates were detected in microsomal incubations, although they were not detected in cryopreserved hepatocytes. These data support ring opening of the furan via a reactive gamma-keto-alpha,beta-unsaturated aldehyde intermediate. In the presence of UDP-glucuronic acid, prazosin underwent conjugation to form an N-glucuronide not reported previously. Our in vitro investigations have revealed additional metabolic transformations of prazosin and have shown the potential of prazosin to undergo bioactivation through metabolism of the furan ring to a reactive intermediate. PMID:17353349

  14. Structure-related inhibitory effect of antimicrobial enoxacin and derivatives on theophylline metabolism by rat liver microsomes.

    PubMed Central

    Mizuki, Y; Fujiwara, I; Yamaguchi, T; Sekine, Y

    1996-01-01

    Enoxacin, an antimicrobial fluoroquinolone with a 7-piperazinyl-1, 8-naphthyridine skeleton, is a potent inhibitor of cytochrome P-450-mediated theophylline metabolism. The present study was designed to clarify, using seven enoxacin derivatives, the molecular characteristics of the fluoroquinolone responsible for the inhibition. Three derivatives with methyl-substituted 7-piperazine rings inhibited rat liver microsomal theophylline metabolism to 1,3-dimethyluric acid to an extent similar to that of enoxacin (50% inhibitory concentrations [IC50s] = 0.39 to 0.48 mM). 7-Piperazinyl-quinoline derivatives, 8-hydroenoxacin (8-Hy) and 1-cyclopropyl-8-fluoroenoxacin (8-F1), which have a hydrogen and a fluorine at position 8, respectively, more weakly inhibited metabolite formation (IC50s = 0.88 and 1.29 mM, respectively). Little inhibition (IC50 > 2 mM) was observed in those with 3'-carbonyl and 4'-N-acetyl groups on the piperazine rings. The substrate-induced difference spectra demonstrated that the affinities of enoxacin, 8-Hy, and 8-F1 to cytochrome P-450 were parallel with their inhibitory activities. The substituent at position 8 was found to determine the molecular conformations of the fluoroquinolones, and the planarity in molecular shape decreased in the same order as the inhibitory activity (enoxacin > 8-Hy > 8-F1). Moreover, the 3'-carbonyl and 4'-N-acetyl groups decreased the basicity of their vicinal 4'-nitrogen atoms when judged from their electrostatic potentials, which showed a remarkably broadened negative charge around the nitrogens. As a result, the planarity of the whole molecule and the basicity of the 4'-nitrogen atom of enoxacin are likely to be dominant factors in the inhibition of theophylline metabolism by cytochrome P-450. PMID:8843297

  15. Simultaneous, quantitative determination of opiates, amphetamines, cocaine and benzoylecgonine in oral fluid by liquid chromatography quadrupole-time-of-flight mass spectrometry.

    PubMed

    Mortier, Kjell A; Maudens, Kristof E; Lambert, Willy E; Clauwaert, Karine M; Van Bocxlaer, Jan F; Deforce, Dieter L; Van Peteghem, Carlos H; De Leenheer, André P

    2002-11-01

    A method using liquid chromatography coupled to tandem mass spectrometry is described for the determination of drugs of abuse in oral fluid. The method is able to simultaneously quantify amphetamines (amphetamine, methamphetamine, MDA, MDMA and MDEA), opiates (morphine and codeine), cocaine and benzoylecgonine. Only 200 micro of oral fluid is spent for analysis. The sample preparation is easy and consists of mixed mode phase solid-phase extraction. Reversed-phase chromatography is carried out on a narrow bore phenyl type column at a flow-rate of 0.2 ml/min. A gradient is applied ranging from 6 to 67.6% methanol with ammonium formate (10 mM, pH 5.0) added to the mobile phase. The column effluent was directed into a quadrupole-time-of-flight instrument by electrospray ionization, without the use of a splitter. A validation study was carried out. Recovery ranged from 52.3 to 98.8%, within-day and between-day precision expressed by relative standard deviation were less than 11.9 and 16.8%, respectively, and inaccuracy did not exceed 11.6%. The limit of quantification was 2 ng/ml (0.66 x 10(-5)-1.48 x 10(-5) M) for all compounds. Internal standards were used to generate quadratic calibration curves (r(2)>0.999). The method was applied to real samples obtained from suspected drug users. An interference was observed from the device used to sample the oral fluid, consequently this was excluded from the method which was validated on oral fluid obtained by spitting in a test-tube. PMID:12361746

  16. Impaired cognitive performance in drug free users of recreational ecstasy (MDMA)

    PubMed Central

    Gouzoulis-Mayfran..., E.; Daumann, J.; Tuchtenhagen, F.; Pelz, S.; Becker, S.; Kunert, H.; Fimm, B.; Sass, H.

    2000-01-01

    OBJECTIVES—Ecstasy (3,4-methylenedioxymethamphetamine (MDMA) and related congerers: MDA, MDEA) is the name given to a group of popular recreational drugs. Animal data raise concern about neurotoxic effects of high doses of ecstasy on central serotonergic systems. The threshold dose for neurotoxicity in humans is not clear and serotonin is involved in several functions including cognition. The purpose of this study was to investigate cognitive performance in a group of typical recreational ecstasy users.?METHODS—A comprehensive cognitive test battery was administered to 28 abstinent ecstasy users with concomitant use of cannabis only and to two equally sized matched groups of cannabis users and non-users. The sample consisted of ecstasy users with a typical recreational use pattern and did not include very heavy users.?RESULTS—Ecstasy users were unimpaired in simple tests of attention (alertness). However, they performed worse than one or both control groups in the more complex tests of attention, in memory and learning tasks, and in tasks reflecting aspects of general intelligence. Heavier ecstasy and heavier cannabis use were associated with poorer performance in the group of ecstasy users. By contrast, the cannabis users did not differ significantly in their performance from the non-users.?CONCLUSIONS—The present data raise concern that use of ecstasy possibly in conjunction with cannabis may lead to cognitive decline in otherwise healthy young people. Although the nature of the emerging cognitive disturbance is not yet clear, an impairment of working memory might be the common denominator underlying or contributing to declines of performance in various tasks. The cognitive disturbance is likely to be related to the well recognised neurotoxic potential of ecstasy. The data suggest that even typical recreational doses of ecstasy are sufficient to cause neurotoxicity in humans.?? PMID:10811694

  17. Mass loading and removal of select illicit drugs in two wastewater treatment plants in New York State and estimation of illicit drug usage in communities through wastewater analysis.

    PubMed

    Subedi, Bikram; Kannan, Kurunthachalam

    2014-06-17

    Sewage epidemiology is a rapidly expanding field that can provide information on illicit drug usage in communities, based on the measured concentrations in samples from wastewater treatment plants (WWTPs). In this study, select illicit drugs (six drugs and eight metabolites) were determined on a daily basis for a week in wastewater, suspended particulate matter (SPM), and sludge from two WWTPs in the Albany area in New York State. The WWTP that served a larger population (?100?000, with a flow rate of 83?300 m(3)/d) showed 3.2 (methadone) to 51 (3,4-methylenedioxyamphetamine; MDA) times higher mass flows of illicit drugs than did the WWTP that served a smaller population (?15?000, with a flow rate of 6850 m(3)/d). The consumption rate of target illicit drugs in the communities served by the two WWTPs was estimated to range from 1.67 to 3510 mg/d/1000 people. Between the dissolved and particulate phases, the fraction of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), amphetamine, and MDA sorbed to SPM ranged from 34.3% to 41.1% of the total mass in the waste stream. The removal efficiencies of illicit drugs from the two WWTPs ranged from 4% (norcocaine) to 99% (cocaine); however, methamphetamine, methadone, and EDDP showed a negative removal in WWTPs. The environmental emission of illicit drugs from WWTP discharges was calculated to range from 0.38 (MDEA) to 67.5 (EDDP) mg/d/1000 people. Other markers such as caffeine, paraxanthine, nicotine, and cotinine were found to predict the concentrations of select illicit drugs in raw wastewater (r(2) = 0.20-0.79; p ? 0.029). PMID:24865581

  18. Presence of illicit drugs and metabolites in influents and effluents of 25 sewage water treatment plants and map of drug consumption in France.

    PubMed

    Nefau, Thomas; Karolak, Sara; Castillo, Luis; Boireau, Véronique; Levi, Yves

    2013-09-01

    Consumption of illicit drugs is a new concern for water management that must be considered not only because of the social and public health aspects but also in an environmental context in relation with the contamination of surface waters. Indeed, sewage treatment plant (STP) effluents contain drug residues that have not been eliminated since STP treatments are not completely efficient in their removal. We developed and validated an HPLC-MS/MS analytical method to assess the concentrations of 17 illicit drugs and metabolites in raw urban wastewaters: cocaine and its metabolites, amphetamine and amphetamine-likes (methamphetamine, MDMA, MDEA, MDA), opiates and opiate substitutes (methadone and buprenorphine), and THC-COOH cannabis metabolite. This method has been applied to the analysis of influent and effluent samples from 25 STPs located in France all over the country. The results allowed evaluating the drug consumption in the areas connected to the STPs and the efficiency of the treatment technology implied. We selected STPs according to their volume capacity, their treatment technologies (biofilters, activated sludges, MBR) and their geographical location. In influents, the concentrations varied between 6 ng/L for EDDP (main metabolite of methadone) and 3050 ng/L for benzoylecgonine (cocaine metabolite). Consumption maps were drawn for cocaine, MDMA, opiates, cannabis and amphetamine-like compounds. Geographical significant differences were observed and highlighted the fact that drug consumption inside a country is not homogeneous. In parallel, comparisons between STP technology processes showed differences of efficiency. More, some compounds appear very resistant to STP processes leading to the contamination of receiving water. PMID:23770552

  19. Metabolism of designer drugs of abuse: an updated review.

    PubMed

    Meyer, Markus R; Maurer, Hans H

    2010-06-01

    This paper reviews the metabolism of new designer drugs of abuse that have emerged on the black market during the last years and is an update of a review published in 2005. The presented review contains data concerning the so-called 2C compounds (phenethylamine type) such as 4-bromo-2,5-dimethoxy-beta-phenethylamine (2C-B), 4-iodo-2,5-dimethoxy-beta-phenethylamine (2C-I), 2,5-dimethoxy-4-methyl-beta-phenethylamine (2C-D), 4-ethyl-2,5-dimethoxy-beta-phenethylamine (2C-E), 4-ethylthio-2,5-dimethoxy-beta-phenethylamine (2C-T-2), and 2,5-dimethoxy-4-propylthio-beta-phenethylamine (2C-T-7), beta-keto designer drugs such as 2-methylamino-1-(3,4-methylenedioxyphenyl)butan-1-one (butylone, bk-MBDB), 2-ethylamino-1-(3,4-methylenedioxyphenyl)propan-1-one (ethylone, bk-MDEA), 2-methylamino-1-(3,4-methylene notdioxy notphenyl)propan-1-one (methylone, bk-MDMA), and 2-methylamino-1-p-tolylpropane-1-one (mephedrone, 4-methyl-methcathinone), pyrrolidino notphenones such as 4-methyl-pyrrolidinobutyrophenone (MPBP) and alpha-pyrrolidinovalerophenone (PVP), phencyclidine-derived drugs such as N (1 phenylcyclohexyl) propanamine (PCPr), N-(1-phenylcyclohexyl)-2-ethoxyethanamine (PCEEA), N-(1-phenylcyclohexyl)-3-methoxypropanamine (PCMPA), and N-(1-phenylcyclohexyl)-2-methoxyethanamine (PCMEA), tryptamines such as 5-methoxy-N,N-diisopropyl nottryptamine (5-MeO-DIPT), and finally alpha-methylfentanyl (alpha-MF) and 3-methylfentanyl (3-MF). Papers have been considered and reviewed on the identification of in vivo or in vitro human or animal metabolites and the cytochrome P450 or monoamineoxidase isoenzyme-dependent metabolism. PMID:20540700

  20. Molecular nanomagnets: Syntheses and characterization of high nuclearity transition metal complexes

    NASA Astrophysics Data System (ADS)

    Foguet-Albiol, Maria D.

    2006-12-01

    High nuclearity transition metal complexes have attracted a lot of attention because of their aesthetically pleasant structures and/or their potential applications. The fusion of the world of magnetism with the exciting research in physics and chemistry led to the realization of interesting types of materials that can function as nanoscale magnetic particles. The study of the magnetism of inorganic complexes and especially the study of these molecular nanomagnets (or single-molecule magnets, SMMs) is a field that has generated intense interest in the scientific community. Interest in these molecular nanomagnets arises as part of a broader investigation of nanomagnetism (and nanotechnology), as these represent the ultimate step in device miniaturization. The primary purpose of this dissertation is the development of new synthetic methods intended for the preparation of novel single-molecule magnets (SMMs). The definition of the "bottom-up approach" is to increase the size of molecules by adding new magnetic centers; this is attractive but does not actually reflect how the chemistry takes place. Various strategies have been employed in developing the aforementioned synthetic methods which include the use of mononuclear as well as preformed clusters as starting materials; and the introduction of new alcohol based ligands as N-methyldiethanolamine (mdaH2) and triethanolamine (teaH3), since currently only a few alcohol based ligands have been used by different research groups. Many of these efforts have led to the isolation of new polynuclear Mn clusters with nuclearities ranging all the way from four to thirty-one. Additionally, a family of related Fe7 complexes has been synthesized. The transition metal cluster chemistry has also been extended to nickel-containing species. Many of these polynulear transition metal complexes function as single-molecule magnets. An additional research direction discussed herein is the study of the exchange-coupled dimer of single-molecule magnets (SMMs) by previously unemployed techniques (i.e., inelastic neutron scattering (INS)). This latter study resulted in a better understanding of the effects of chemical and physical variations on the magnetic parameters S, D and J. These studies provide insight into approaches necessary to gain access to clusters that behave as single-molecule magnets at more technologically relevant temperatures, an issue of growing concern as the research area further matures.

  1. Novel benzodioxopiperazines acting as antagonists at postsynaptic 5-HT1A receptors and as agonists at 5-HT1A autoreceptors: a comparative pharmacological characterization with proposed 5-HT1A antagonists.

    PubMed

    Millan, M J; Canton, H; Gobert, A; Lejeune, F; Rivet, J M; Bervoets, K; Brocco, M; Widdowson, P; Mennini, T; Audinot, V

    1994-01-01

    The novel benzodioxopiperazines [4-(benzodioxan-5-yl)1-[2- (benzocyclobutane-1-yl)ethyl]piperazine] (S 14489), [4-(benzodioxan-5-yl)1-(indan-2-yl)piperazine)] (S 15535) and [4-(benzodioxan-5-yl)1-[2(indan-1-yl)ethyl]piperazine (S15931) competitively displaced the binding of [3H]-8-OH-DPAT at serotonin (5-HT)1A receptors with affinities (pKis) of 9.2, 8.8 and 8.9, respectively. These values compared favorably with those of the structurally related eltoprazine (8.0) and the proposed 5-HT1A antagonists NAN-190 (9.2), MDL 73005 EF (8.9), SDZ 216-525 (8.8), BMY 7378 (8.7), (-)-tertatolol (8.1), (-)-alprenolol (7.7), WAY 100,135 (7.5) and spiperone (6.9). The affinities of S 14489, S 15535 and S 15931 for other 5-HT receptor types (5-HT1B, 5-HT1C, 5-HT1D, 5-HT2 and 5-HT3) were about 50 to 1000-fold lower. The spontaneous tail-flicks, flat-body posture and hypothermia mediated by an action of the 5-HT1A agonist 8-OH-DPAT at postsynaptic 5-HT1A receptors were dose-dependently and completely antagonized by S 14489, S 15535 and S15931 at doses of 0.63 to 10.0 and 2.5 to 40.0 mg/kg for s.c. and oral administration, respectively. They did not induce these responses alone, and in their presence, dose-response curves for 8-OH-DPAT were shifted in parallel to the right without loss of maximal effect. By contrast, eltoprazine, MDL 73005 EF, BMY 7378 and NAN-190 behaved as "partial" agonists and only incompletely antagonized the actions of 8-OH-DPAT in these tests. At 5-HT1A autoreceptors, S 14489, S 15535 and S 15931 acted as agonists in inhibiting striatal 5-hydroxytryptophan accumulation (0.16-2.5 mg/kg, s.c.) and in abolishing the electrical activity of the dorsal raphe nucleus (0.005-0.100 mg/kg, i.v.). Eltoprazine, BMY 7378, NAN-190 and MDL 73005 EF also behaved as agonists at these 5-HT1A autoreceptors, whereas WAY 100,135, spiperone, (-)-tertatolol, (-)-alprenolol and SDZ 216-525 inhibited neither accumulation nor firing. WAY 100,135 and spiperone antagonized the inhibition of DRN firing induced by S 14489, S 15535 and S 15931. The affinity of 15535 for dopamine D1 and D2 receptors, as well as for beta-, alpha 1- and alpha 2-adrenoceptors, was > 100-fold lower than its affinity for 5-HT1A receptors. Further, in vivo, at doses of 10.0 to 40.0 mg/kg, s.c., it showed minimal activity in tests of dopamine D2 (and D1) receptor-mediated activity. Similarly, in vivo, S 15535 was weakly active in a test of alpha 1-adrenoceptor-mediated activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8301575

  2. Hydrothermal synthesis, crystal structure, thermal behavior and spectroscopic and magnetic properties of two new organically templated fluoro-vanadyl-hydrogenarsenates: (R){sub 0.5}[(VO)(HAsO{sub 4})F] (R: Ethylenediammonium and piperazinium)

    SciTech Connect

    Berrocal, Teresa [Departamento de Mineralogia y Petrologia, Facultad de Ciencia y Tecnologia, Universidad del Pais Vasco/EHU Apdo. 644, E-48080 Bilbao (Spain); Mesa, Jose L. [Departamento de Quimica Inorganica, Facultad de Ciencia y Tecnologia, Universidad del Pais Vasco/EHU Apdo. 644, E-48080 Bilbao (Spain)], E-mail: joseluis.mesa@ehu.es; Pizarro, Jose L. [Departamento de Mineralogia y Petrologia, Facultad de Ciencia y Tecnologia, Universidad del Pais Vasco/EHU Apdo. 644, E-48080 Bilbao (Spain); Lezama, Luis [Departamento de Quimica Inorganica, Facultad de Ciencia y Tecnologia, Universidad del Pais Vasco/EHU Apdo. 644, E-48080 Bilbao (Spain); Bazan, Begona; Arriortua, Maria I. [Departamento de Mineralogia y Petrologia, Facultad de Ciencia y Tecnologia, Universidad del Pais Vasco/EHU Apdo. 644, E-48080 Bilbao (Spain); Rojo, Teofilo [Departamento de Quimica Inorganica, Facultad de Ciencia y Tecnologia, Universidad del Pais Vasco/EHU Apdo. 644, E-48080 Bilbao (Spain)

    2008-04-15

    Two new fluoro-vanadyl-hydrogenarsenate compounds templated by ethylenediamine and piperazine with formula, (C{sub 2}N{sub 2}H{sub 10}){sub 0.5}[(VO)(HAsO{sub 4})F] (1) and (C{sub 4}N{sub 2}H{sub 12}){sub 0.5}[(VO)(HAsO{sub 4})F] (2), respectively, have been synthesized by using mild hydrothermal conditions under autogenous pressure. The crystal structures have been solved from single-crystal X-ray diffraction data. The phases crystallize in the P2{sub 1}/c monoclinic space group with the unit-cell parameters a=7.8634(4) A, b=7.7658(4) A, c=10.4195(6) A, {beta}=101.524(5){sup o} for compound (1) and a=6.301(1) A, b=10.244(1) A, c=10.248(1) A and {beta}=95.225(1){sup o} for compound (2). These phases exhibit a layered inorganic framework. In both cases, the structure is built from secondary building units (SBU) which are formed by [V{sub 2}O{sub 8}F{sub 2}] edge-shared dimeric vanadyl octahedra, connected by the vertices to two hydrogenarsenate tetrahedra. The repetition of this SBU unit originates sheets along the [1 0 0] direction. The ethylenediammonium and piperazinium cations are located inside the interlayer space. The limit of thermal stability for compounds (1) and (2) is, approximately, 250 and 230 deg. C, respectively. Near this temperature, both phases loose their organic cations and the fluoride anions. The diffuse reflectance spectra confirm the presence of vanadyl ions, in which the vanadium(IV) cations have a d{sup 1} electronic configuration in a slightly distorted octahedral environment. ESR spectra of both phases are isotropic with mean g-values of 1.93 and 1.96 for ethylendiamine and piperazine phases, respectively. Magnetic measurements for (1) and (2) indicate the existence of antiferromagnetic exchange couplings. - Graphical abstract: Polyhedral view of the layered crystal structure of (C{sub 2}H{sub 10}N{sub 2}){sub 0.5} [(VO)(HAsO{sub 4})F].

  3. (1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane)-induced head-twitches in the rat are mediated by 5-hydroxytryptamine (5-HT) 2A receptors: modulation by novel 5-HT2A/2C antagonists, D1 antagonists and 5-HT1A agonists.

    PubMed

    Schreiber, R; Brocco, M; Audinot, V; Gobert, A; Veiga, S; Millan, M J

    1995-04-01

    In this study, the involvement of serotonergic and dopaminergic receptors in the modulation of the head-twitch (HTW) response to the 5-hydroxytryptamine (5-HT)2A/5-HT2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, was characterized in rats using novel and selective ligands at 5-HT2A, 5-HT2C, D1, D2 and 5-HT1A receptors. HTW were dose-dependently inhibited by the 5-HT2A/2C antagonists, ritanserin, metergoline, mesulergine, mianserin, ICI 169,369 and LY 58,537, by the preferential 5-HT2A antagonist, ketanserin and by the novel, selective 5-HT2A antagonist, SR 46349B. A further selective 5-HT2A antagonist, MDL 100,907, very potently abolished HTW (ED50 = 0.005 mg/kg). The order of relative potency correlated highly with their affinity at 5-HT2A (r = 0.83) but not 5-HT2C receptors (r = 0.06). In addition, the novel, selective 5-HT2C antagonist, SB 200,646A, failed to abolish HTW and the 5-HT2C agonists/5-HT2A antagonists, 1-(3-chlorophenyl)piperazine and 1-(3-trifluoromethylphenyl)piperazine, blocked, rather than elicited, HTW. The D1 antagonists, SCH 23390, NNC 112, NNC 756, SCH 39166 and A 69024, in this order of relative potency that correlated with their affinity at D1 receptors (r = 0.98), blocked HTW. The D2 antagonists, raclopride, eticlopride and haloperidol also blocked HTW. The 5-HT1A agonists, S 14671, S 14506, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, ipsapirone and (+)-flesinoxan, abolished HTW. The action of 8-hydroxy-2-(di-n-propylamino)tetralin was blocked by (-)-tertatolol (ID50 = 4.5 mg/kg), a novel 5-HT1A receptor antagonist. Similarly, (-)-tertatolol attenuated the action of S 14506 and abolished that of S 14671, buspirone and ipsapirone. A role of postsynaptic 5-HT1A receptors in the action of 5-HT1A agonists was suggested by the finding that parachlorophenylalanine (3 x 300 mg/kg, i.p.), which depleted cerebral pools of 5-HT, did not modify the activity of ipsapirone. The present data demonstrate that 5-HT2A receptors mediate HTW in rats and that both D1 and D2 receptors as well as (postsynaptic) 5-HT1A receptors play a role in their expression. PMID:7714755

  4. Selective in vivo labelling of brain 5-HT1A receptors by [3H]WAY 100635 in the mouse.

    PubMed

    Laporte, A M; Lima, L; Gozlan, H; Hamon, M

    1994-12-27

    The novel selective 5-HT1A receptor antagonist radioligand [3H]WAY 100635 ([O-methyl-3H]N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2- pyridyl)cyclohexane-carboxamide) was injected i.v. to mice in an attempt to label in vivo central 5-HT1A receptors. Although 5 min after the i.v. injection of [3H]WAY 100635 (4-7.6 muCi per mouse) the amount of tritium found in the whole brain only accounted for 1.5-1.8% of the injected radioactivity, regional differences in 3H accumulation already corresponded to those of 5-HT1A receptor density. Optimal data were obtained 1 h after [3H]WAY 100635 injection as the distribution of 3H in brain was exactly that of 5-HT1A receptor binding sites in mouse brain sections labelled in vitro with [3H]WAY 100635. In particular, high level of labelling was found in the lateral septum, gyrus dentatus and CA1 area of Ammon's horn in the hippocampus, dorsal raphe nucleus and entorhinal cortex. No labelling was found in he substantia nigra, and 3H accumulated in the cerebellum represented only 12-14% of that found in the hippocampus. Pretreatment with various drugs indicated that only 5-HT1A receptor ligands were able to decrease the accumulation of 3H in all the brain areas examined except in the cerebellum. Assuming that only non-specific binding took place in the latter structure, it was possible to calculate the ID50 values of 5-HT1A receptor agonists (8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), S 14506 (1-[2-(4-fluorobenzoylamino)ethyl]-4-(7-methoxynaphthyl+ ++)piperazine) and S 20499 ((+)-4-[N-(5-methoxy-chroman-3-yl)-N-propylamino]butyl-8- azaspiro-(4,5)-decane-7,9-dione)) and antagonists (spiperone, (-)-tertatolol, (+)-WAY 100135 (N-tert-butyl-3,4-(2-methoxyphenyl)piperazin-1-yl-2-phenyl- propanamide)) as inhibitors of 3H accumulation in the hippocampus of [3H]WAY 100635-injected mice. Comparison of these values with the in vitro affinity of the same ligands for hippocampal 5-HT1A receptors revealed marked variations in the capacity of 5-HT1A receptor agonists and antagonists to reach the brain when injected via the subcutaneous route in mice. PMID:7705451

  5. BIMT 17, a 5-HT1A receptor agonist/5-HT2A receptor antagonist, directly activates postsynaptic 5-HT inhibitory responses in the rat cerebral cortex.

    PubMed

    Borsini, F; Ceci, A; Bietti, G; Donetti, A

    1995-09-01

    BIMT 17 (1-[2-[4-(3-trifluoromethyl phenyl) piperazin-1-yl] ethyl] benzimidazol- [1H]-2-one), a 5-HT1A receptor agonist/5-HT2A receptor antagonist (see Borsini et al., accompanying paper), in a dose range of 1-10 mg/kg i.v., dose-dependently inhibited the electrical activity of rat medial prefronto-cortical neurons, whereas buspirone, in a dose range of 0.1-1000 micrograms/kg, increased it. 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and 1-[2-(2-thenoylamino)ethyl]-4-[1-(7-methoxynaphthyl)] piperazine (S 14671) presented biphasic patterns of response; they increased electrical activity at doses in the range of 0.1-10 micrograms/kg and 0.1-3 micrograms/kg i.v. respectively, and reduced it at high doses, 30-300 micrograms/kg and 10-30 micrograms/kg i.v., respectively. The inhibitory effect of BIMT 17 on the firing rate of neurons in the frontal cortex was antagonized by the 5-HT1A antagonists tertatolol and WAY 100135, and was still present after destruction of serotonin (5-HT) containing neuronal endings by the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 150 micrograms/rat, given intraventricularly), which reduced the cortical 5-HT content by 85%. This destruction of 5-HT neurons, while suppressing the ability of 8-OH-DPAT to inhibit the firing rate at high doses, did not change the excitatory action of this compound at low doses. The addition of ritanserin, a 5-HT2A receptor antagonist, potentiated both the excitatory and inhibitory effects of 8-OH-DPAT on neuronal electrical activity. Direct microiontophoretic application (100 nA/20 s) of 5-HT and BIMT 17, but not that of 8-OH-DPAT, onto medial prefronto-cortical neurons, decreased the firing rate of these neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8584043

  6. Serotonin-mediated inhibitory postsynaptic potential in guinea-pig prepositus hypoglossi and feedback inhibition by serotonin.

    PubMed

    Bobker, D H; Williams, J T

    1990-03-01

    1. Intracellular recordings were made from neurones of the nucleus prepositus hypoglossi (PH) in slices of guinea-pig brain. Focal stimulation evoked an inhibitory postsynaptic potential (IPSP) that was typically 10-25 mV in amplitude and 1 s in duration. The IPSP reversal potential showed a Nernstian dependence on the external potassium concentration ([K+]o). 2. Spiperone blocked the IPSP with an IC50 of 40 nM, while ketanserin and (-)sulpiride had no effect. Cocaine (1 microM) prolonged the IPSP half-duration by 157%, and increased the amplitude by 28%. 3. 5-Hydroxytryptamine (5-HT, serotonin) hyperpolarized PH cells with an EC50 of 8.5 microM in control, and 135 nM in cocaine (10 microM). 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) also hyperpolarized PH cells with an EC50 of 16 nM, although the maximal effect was only 81% of the maximum 5-HT hyperpolarization. Spiperone produced a parallel, right shift of the 5-HT concentration-response curve; Schild analysis gave a Kd of 10 nM. Application of 5-HT to neurones voltage-clamped near their resting potential (about -55 mV) caused an outward current and an increase in membrane conductance. 4. The amplitude of the IPSP was reversibly decreased by non-hyperpolarizing concentrations of 5-HT and by the 5-HT1 receptor agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP) and 1-(3-chlorophenyl)piperazine (mCPP). The IC50 values for the latter two compounds were 50 nM and 1.5 microM, respectively; the maximal effect was a 90% inhibition. Neither compound affected the membrane potential nor changed the hyperpolarization induced by 5-HT. Quipizine competitively antagonized TFMPP with an estimated Kd of 165 nM. 5. When trains of stimuli were applied, an inhibition of the IPSP was observed following the first stimulus. At a frequency of 1 Hz, the inhibition was approximately 75%. This frequency-dependent 'run-down' of the IPSP was markedly attenuated by pre-treatment with TFMPP (1 microM). 6. It is concluded that the IPSP in PH cells is caused by 5-HT acting on 5-HT1A receptors to activate a potassium conductance. The release of 5-HT can be inhibited by activation of a presynaptic 5-HT1D receptor. This presynaptic receptor appears to be at least partly responsible for the run-down phenomenon, and may be involved in the physiological regulation of 5-HT synaptic transmission. PMID:2141079

  7. Design, synthesis and biological evaluation of bivalent benzoxazolone and benzothiazolone ligands as potential anti-inflammatory/analgesic agents.

    PubMed

    Abdelazeem, Ahmed H; Khan, Shabana I; White, Stephen W; Sufka, Kenneth J; McCurdy, Christopher R

    2015-07-01

    Benzoxazolone and benzothiazolone were used as template blocks to develop two series of dimers as anti-inflammatory and analgesic agents based on the concept of bivalent ligands. The first series (I) involved varying the carbon chain lengths extending from the piperazine core to the nitrogen atom of the dibenzo[d]oxazol-2(3H)-one or dibenzo[d]thiazol-2(3H)-one. The second series (II) was designed by changing the attachment point. All compounds were screened for their in vitro anti-inflammatory activity in terms of the inhibition of inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-?B). Seventeen compounds inhibited both targets. Eleven of them exhibited IC50 values below 3?M while five compounds showed IC50 values of 1?M or below. Most of the compounds were found to be devoid of cytotoxicity against mammalian kidney and solid tumors cell lines up to 25?g/mL. In vivo anti-inflammatory and antinociceptive studies revealed that compounds 3j, 5t and 8b have significant anti-inflammatory and analgesic activity comparable to that of indomethacin and ketorolac, respectively. PMID:25975638

  8. The cardioprotective effect of TG-6, a newly synthesized compound, on ischemia-reperfusion injury in rats.

    PubMed

    Zhou, Yi; Gong, Guoqing; Yang, Wenhui; Wang, Yin; Xu, Jing; Xu, Yungen

    2012-05-15

    We tested 3-nitro-4-((4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)methyl) benzoylguanidine tartrate (TG-6) which is combinated of two known cardioprotective agents cariporide and trimetazidine, whether additively to reduce ischemia-reperfusion injury in rats. Using models of in vitro perfusion (Langendorff system) and in vivo open chest left anterior descending coronary artery ligation causing ischemia-reperfusion injury. We also used Fura-2 to measure the cytosolic Ca²? concentrations ([Ca²?]i) in cardiomyocytes, western blot analysis the protein expression of Kv1.4, Kv4.2, Kv4.3 in myocardial ischemia-reperfusion rats. TG-6 improved the cardiac function in both in vivo and in vitro models, lowered Lactate Dehydrogenase (LDH), Creatine Kinase (CK), Malodialdehyed (MDA) activity while enhanced Superoxide Dismutase (SOD) activity. High dose of TG-6 improved the hypoxia injury of cardiomyocytes induced by sodium dithionite (Na?S?O?), enhanced the viability and decreased the [Ca²?]i. It also down-regulated the expression of Kv1.4 and increased the expression of Kv4.2 and Kv4.3, so it might through regulating the expression of the transient outward potassium current (Ito) to improve the cardiac function. PMID:22425651

  9. 1H, 13C NMR studies and GIAO/DFT calculations of substituted N-(4-aryl-1-piperazinylbutyl) derivatives, new analogues of buspirone

    NASA Astrophysics Data System (ADS)

    Pisklak, Maciej; Kossakowski, Jerzy; Perli?ski, Miros?aw; Wawer, Iwona

    2004-07-01

    13C cross-polarisation (CP) magic angle spinning (MAS) NMR data are reported for seven piperazinylbutyl derivatives of 1,4-dichloro-dibenzo[ e, h]bicyclo[2,2,3]octane-2,3-dicarboimide, new analogues of buspirone (anxiolytic drug). The assignment of solid state 13C NMR spectra were made with an aid of variable contact time experiments, as well as by comparison with solution data and calculated shielding constants. 13C CPMAS NMR spectra showed a disorder of methylene carbons in solids of 1- 7, in 1 and 3 two molecules differing in conformation of n-butyl chain are probably present in the asymmetric unit cell. In CDCl 3 solution, the barrier to piperazine ring inversion is 50 kJ/mol for 2, and lower than 46 kJ/mol for 1 and 3. Satisfactory agreement between the experimental chemical shifts (both in solution and solid state) and theoretical values of shielding constants (calculated by GIAO/DFT and GIAO/HF methods) was obtained (correlation coefficients R2>0.98).

  10. Influence of the crosslinker type on the chromatographic properties of hydrophilic sulfoalkylbetaine-type monolithic columns.

    PubMed

    Liu, Chusheng; Chen, Weijia; Yuan, Guangxin; Xiao, Yao; Crommen, Jacques; Xu, Shihai; Jiang, Zhengjin

    2014-12-19

    In order to investigate the effects of the crosslinker on the separation performance of polar zwitterionic sulfoalkylbetaine-type monolithic columns, three crosslinkers, i.e. 1,4-bis(acryloyl)piperazine (PDA), ethylene dimethacrylate (EDMA) and N,N'-methylenebisacrylamide (MBA), were copolymerized with the hydrophilic monomer N,N-dimethyl-N-acryloyloxyethyl-N-(3-sulfopropyl)ammonium betaine (SPDA). The chromatographic properties of the three hydrophilic sulfoalkylbetaine-type monolithic columns, including column efficiency, permeability, porosity and separation mechanism, were systematically compared using scanning electron microscopy or micro-HPLC. Good selectivity in micro-HPLC separations was achieved on all three monolithic columns. The results indicate that the polarity of sulfoalkylbetaine-type monolithic columns may be related to the polarity of the crosslinker, which further affects column selectivity and efficiency. A particularly high column efficiency (100,000 plates/m) was obtained on the novel poly(SPDA-co-PDA) monolithic column at a linear velocity of 1mm/s using thiourea as test analyte. A higher resolution was also observed for nucleobases, nucleosides and hydrophilic organic acids on this novel poly(SPDA-co-PDA) monolithic column compared to the other two columns. PMID:25464999

  11. Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT1A activity. Part 5.

    PubMed

    Gomó?ka, Anna; Ciesielska, Agnieszka; Wróbel, Martyna Z; Chodkowski, Andrzej; Kleps, Jerzy; Dawidowski, Maciej; Siwek, Agata; Wolak, Ma?gorzata; Stachowicz, Katarzyna; S?awi?ska, Anna; Nowak, Gabriel; Sata?a, Grzegorz; Bojarski, Andrzej J; Belka, Mariusz; Ulenberg, Szymon; B?czek, Tomasz; Skowronek, Pawe?; Tur?o, Jadwiga; Herold, Franciszek

    2015-06-15

    A series of novel 4-aryl-pyrido[1,2-c]pyrimidine derivatives containing a 1-(2-quinoline)piperazine moiety was synthesized. The chemical structure of new compounds was confirmed by FT-IR, (1)H NMR, (13)C NMR and HRMS spectra as well as elemental analysis. Affinity of the novel pyrido[1,2-c]pyrimidine derivatives for 5-HT1A, 5-HT2A receptors and serotonin transporter (SERT) was evaluated in an in vitro radioligand binding assay. Tested compounds showed moderate to high affinity for 5-HT1AR and SERT and low affinity for 5-HT2AR. Selected ligands were subjected to in vivo tests, such as induced hypothermia and the forced swimming test in mice, which determined presynaptic agonistic activity of the ligands 8d, 8e, 9d and 9e and presynaptic antagonistic activity of the ligands 8a, 8b, 9a, 9b. Additionally, metabolic stability evaluation was performed for selected ligands, proving that a para-substitution in the 4-aryl-pyrido[1,2-c]pyrimidine moiety leads to an increase in stability, whereas a substitution in the ortho-position lowers the stability. PMID:26043160

  12. Parasiticidal and brine shrimp cytotoxicity potential of crude methanolic extract of rind of Punica granatum Linn against round worms and tape worms.

    PubMed

    Ali, Niaz; Jamil, Ayesha; Shah, Syed Wadood Ali; Shah, Ismail; Ahmed, Ghayour; Junaid, Muhammad; Ahmed, Zahoor

    2015-05-01

    Rind of Punica granatum is traditionally used for anthelmintic purposes. The current work describes the possible anthelmintic activity of crude methanolic extract of Punica granatum (Pg. Cr) against round worms (Ascaridia galli) and the tape worms (Raillietina spiralis). Brine shrimp cytotoxicity is also performed. Brine shrimp cytotoxic activity was tested using different concentrations (1000 ?g/mL, 100 ?g/mL and 10 ?g/mL) of Pg.Cr. In vitro anthelmintic activity of Pg. Cr was determined against the parasites using albendazole and piperazine citrate as standard anthelmintic drugs in concentration 10 mg/ml. LC50 value for Brine shrimp cytotoxicity was 189.44 ±28 ?g/mL. In test concentration of 40mg/ml of the Pg. Cr, Raillietina spiralis was paralyzed in 23 minutes. However, for parasiticidal activity (death of the parasite), it took less time (40 minutes) as compared to standard Albendazole. Time taken for death of the parasite Raillietina spiralis, in concentration 40 mg /ml, is 40 min. While standard drugs took more time to kill the Raillietina spiralis. Pg. Cr took 19 minutes to paralyze the Ascaridia galli at concentration 40 mg/ml whereas; it took 48 minutes for to kill the parasite Ascaridia galli. The current work confirms the traditional use of rind of Punica granatum as anthelmintic against Raillietina spiralis and Ascaridia galli. Results of brine shrimp cytotoxicity assay warrant for the isolation of cytotoxic compounds. List of abbreviation- Pg. Cr = Crude methanolic extract of Punica granatum. PMID:26004729

  13. Combinatorial synthesis of chemically diverse core-shell nanoparticles for intracellular delivery

    PubMed Central

    Siegwart, Daniel J.; Whitehead, Kathryn A.; Nuhn, Lutz; Sahay, Gaurav; Cheng, Hao; Jiang, Shan; Ma, Minglin; Lytton-Jean, Abigail; Vegas, Arturo; Fenton, Patrick; Levins, Christopher G.; Love, Kevin T.; Lee, Haeshin; Cortez, Christina; Collins, Sean P.; Li, Ying Fei; Jang, Janice; Querbes, William; Zurenko, Christopher; Novobrantseva, Tatiana; Langer, Robert; Anderson, Daniel G.

    2011-01-01

    Analogous to an assembly line, we employed a modular design for the high-throughput study of 1,536 structurally distinct nanoparticles with cationic cores and variable shells. This enabled elucidation of complexation, internalization, and delivery trends that could only be learned through evaluation of a large library. Using robotic automation, epoxide-functionalized block polymers were combinatorially cross-linked with a diverse library of amines, followed by measurement of molecular weight, diameter, RNA complexation, cellular internalization, and in vitro siRNA and pDNA delivery. Analysis revealed structure-function relationships and beneficial design guidelines, including a higher reactive block weight fraction, stoichiometric equivalence between epoxides and amines, and thin hydrophilic shells. Cross-linkers optimally possessed tertiary dimethylamine or piperazine groups and potential buffering capacity. Covalent cholesterol attachment allowed for transfection in vivo to liver hepatocytes in mice. The ability to tune the chemical nature of the core and shell may afford utility of these materials in additional applications. PMID:21784981

  14. Crystal structure of a mixed solvated form of amoxapine acetate

    PubMed Central

    Bhardwaj, Rajni M.; Raval, Vishal; Oswald, Iain D. H.; Florence, Alastair J.

    2015-01-01

    The mixed solvated salt 4-(2-chloro­dibenzo[b,f][1,4]oxazepin-11-yl)piperazin-1-ium acetate–acetic acid–cyclo­hexane (2/2/1), C17H17ClN3O+·C2H3O2 ?·C2H4O2·0.5C6H12, crystallizes with one mol­ecule of protonated amoxapine (AXPN), an acetate anion and a mol­ecule of acetic acid together with half a mol­ecule of cyclo­hexane. In the centrosymmetric crystal, both enanti­omers of the protonated AXPN mol­ecule stack alternatively along [001]. Acetate anions connect the AXPN cations through N—H?O hydrogen bonding in the [010] direction, creating a sheet lying parallel to (100). The acetic acid mol­ecules are linked to the acetate anions via O—H?O hydrogen bonds within the sheets. Within the sheets there are also a number of C—H?O hydrogen bonds present. The cyclo­hexane solvent mol­ecules occupy the space between the sheets. PMID:25878802

  15. Activation of the c-Jun N-terminal kinase/activating transcription factor 3 (ATF3) pathway characterizes effective arylated diazeniumdiolate-based nitric oxide-releasing anticancer prodrugs.

    PubMed

    Maciag, Anna E; Nandurdikar, Rahul S; Hong, Sam Y; Chakrapani, Harinath; Diwan, Bhalchandra; Morris, Nicole L; Shami, Paul J; Shiao, Yih-Horng; Anderson, Lucy M; Keefer, Larry K; Saavedra, Joseph E

    2011-11-24

    Improved therapies are needed for nonsmall cell lung cancer. Diazeniumdiolate-based nitric oxide (NO)-releasing prodrugs are a growing class of promising NO-based therapeutics. Recently, we have shown that O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, 1) is effective against nonsmall cell lung cancer (NSCLC) cells in culture and in vivo. Here we report mechanistic studies with compound 1 and its homopiperazine analogue and structural modification of these into more stable prodrugs. Compound 1 and its homopiperazine analogue were potent cytotoxic agents against NSCLC cells in vitro and in vivo, concomitant with activation of the SAPK/JNK stress pathway and upregulation of its downstream effector ATF3. Apoptosis followed these events. An aryl-substituted analogue, despite extended half-life in the presence of glutathione, did not activate JNK or have antitumor activity. The data suggest that rate of reactivity with glutathione and activation of JNK/ATF3 are determinants of cancer cell killing by these prodrugs. PMID:22003962

  16. Nitric Oxide (NO) Releasing Poly ADP-ribose Polymerase 1 (PARP-1) Inhibitors Targeted to Glutathione S-Transferase P1-Overexpressing Cancer Cells

    PubMed Central

    2015-01-01

    We report the antitumor effects of nitric oxide (NO) releasing derivatives of the PARP-1 inhibitor olaparib (1). Compound 5b was prepared by coupling the carboxyl group of 3b and the free amino group of arylated diazeniumdiolated piperazine 4. Analogue 5a has the same structure except that the F is replaced by H. Compound 13 is the same as 5b except that a Me2N–N(O)=NO– group was added para and ortho to the nitro groups of the dinitrophenyl ring. The resulting prodrugs are activated by glutathione in a reaction accelerated by glutathione S-transferase P1 (GSTP1), an enzyme frequently overexpressed in cancers. This metabolism generates NO plus a PARP-1 inhibitor simultaneously, consuming reducing equivalents, leading to DNA damage concomitant with inhibition of DNA repair, and in the case of 13 inducing cross-linking glutathionylation of proteins. Compounds 5b and 13 reduced the growth rates of A549 human lung adenocarcinoma xenografts with no evidence of systemic toxicity. PMID:24521039

  17. Study of polymorphism in imatinib mesylate: A quantum chemical approach using electronic and vibrational spectra

    NASA Astrophysics Data System (ADS)

    Srivastava, Anubha; Joshi, B. D.; Tandon, Poonam; Ayala, A. P.; Bansal, A. K.; Grillo, Damián

    2013-02-01

    Imatinib mesylate, 4-(4-methyl-piperazin-1-ylmethyl)-N-u[4-methyl-3-(4-pyridin-3-yl)pyrimidine-2-ylamino)phenyl]benzamide methanesulfonate is a therapeutic drug that is approved for the treatment of chronic myelogeneous leukemia (CML) and gastrointestinal stromal tumors (GIST). It is known that imatinib mesylate exists in two polymorphic forms ? and ?. However, ?-form is more stable than the ?-form. In this work, we present a detailed vibrational spectroscopic investigation of ?-form by using FT-IR and FT-Raman spectra. These data are supported by quantum mechanical calculations using DFT employing 6-311G(d,p) basis set, which allow us to characterize completely the vibrational spectra of this compound. The FT-IR spectrum of ?-form has also been discussed. The importance of hydrogen-bond formation in the molecular packing arrangements of both forms has been examined with the vibrational shifts observed due to polymorphic changes. The red shift of the NH stretching bands in the infrared spectrum from the computed wavenumber indicates the weakening of the NH bond. The UV-vis spectroscopic studies along with the HOMO-LUMO analysis of both polymorphs (? and ?) were performed and their chemical activity has been discussed. The TD-DFT method was used to calculate the electronic absorption spectra in the gas phase as well as in the solvent environment using IEF-PCM model and 6-31G basis set. Finally, the results obtained complements to the experimental findings.

  18. Synthesis and characterization of novel oxazines and demonstration that they specifically target cyclooxygenase 2.

    PubMed

    Srinivas, V; Mohan, Chakrabhavi Dhananjaya; Baburajeev, C P; Rangappa, Shobith; Jagadish, Swamy; Fuchs, Julian E; Sukhorukov, Alexey Yu; Chandra; Mason, Daniel J; Sharath Kumar, Kothanahally Shivaramu; Madegowda, Mahendra; Bender, Andreas; Basappa; Rangappa, Kanchugarakoppal Subbegowda

    2015-08-01

    In the present study, we used solution combustion synthesis-bismuth oxide (Bi2O3) as catalyst for the simple and efficient synthesis of 1,2-oxazine based derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazoles, 1-arylpiperazine and carbazoles. (4aR,8aR)-4-(4-Methoxyphenyl)-3-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)-4a,5,6,7,8,8a-hexahydro-4H-benzo[e][1,2]oxazine was found to be the most potent compound with a high degree of selectivity in inhibition towards COX2 (1.7?M) over COX1 (40.4?M) demonstrating the significance of 1,2-oxazine derivatives in developing COX2 specific inhibitors. Molecular docking analyses demonstrated that an isoleucine residue in the active site of COX1 is responsible for lower affinity to COX1 and increased potency towards COX2. Overall, our study reveals that the new 1,2-oxazine-based small molecules qualify as lead structures in developing COX2-specific inhibitors for anti-inflammatory therapy. PMID:26048794

  19. Targeting InhA, the FASII Enoyl-ACP Reductase: SAR Studies on Novel Inhibitor Scaffolds

    PubMed Central

    Pan, Pan; Tonge, Peter J.

    2015-01-01

    The bacterial type II fatty acid biosynthesis (FASII) pathway is an essential but unexploited target for drug discovery. In this review we summarize SAR studies on inhibitors of InhA, the enoyl-ACP reductase from the FASII pathway in M. tuberculosis. Inhibitor scaffolds that are described include the diaryl ethers, pyrrolidine carboxamides, piperazine indoleformamides, pyrazoles, arylamides, fatty acids, and imidazopiperidines, all of which form ternary complexes with InhA and the NAD cofactor, as well as isoniazid and the diazaborines which covalently modify the cofactor. Analysis of the structural data has enabled the development of a common binding mode for the ternary complex inhibitors, which includes a hydrogen bond network, a large hydrophobic pocket and a third ‘size-limited’ binding area comprised of both polar and non-polar groups. A critical factor in InhA inhibition involves ordering of the substrate binding loop, located close to the active site, and a direct link is proposed between loop ordering and slow onset enzyme inhibition. Slow onset inhibitors have long residence times on the enzyme target, a property that is of critical importance for in vivo activity. PMID:22283812

  20. Different effects of selective dopamine uptake inhibitors, GBR 12909 and WIN 35428 on HIV-1 Tat toxicity in rat fetal midbrain neurons

    PubMed Central

    Aksenov, Michael Y.; Aksenova, Marina V.; Silvers, Janelle M.; Mactutus, Charles F.; Booze, Rosemarie M.

    2014-01-01

    Drug abuse is a risk factor for neurological complications in HIV infection. Cocaine has been shown to exacerbate HIV-associated brain pathology and enhance neurotoxicity of HIV-1 Tat and gp120 proteins. In this study, we found that the selective inhibitor of dopamine transporter (DAT) function, 1-[2-[bis(4- fluorophenyl) methoxy]ethyl]-4-(3-phenylpropyl) piperazine (GBR 12909, vanoxerine), but not the selective inhibitors of serotonin and norepinephrine (SERT and NET) transporters, sertraline and nizoxetine, emulated cocaine-mediated enhancement of Tat neurotoxicity in rat fetal midbrain primary cell cultures. Similar to cocaine, the significant increase of Tat toxicity in midbrain cell cultures was observed at micromolar dose (5 ?M) of GBR 12909. However, different doses of another selective dopamine uptake inhibitor, WIN 35428 did not affect Tat neurotoxicity. The study supports the hypothesis that changes in control of dopamine (DA) homeostasis are important for the cocaine-mediated enhancement of HIV-1 Tat neurotoxicity. Our results also demonstrate that the inhibitors of DA uptake, which can bind to different domains of DAT, differ in their ability to mimic synergistic toxicity of cocaine and HIV-1 Tat in the midbrain cell culture. PMID:18606182

  1. Construction of two novel indium phosphites with (3,6)- and (3,5)-connected frameworks: Synthesis, structure and characterization

    SciTech Connect

    Li Huiduan [State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China); Department of Chemistry and Life Science, Chuxiong Normal University, Chuxiong 675000 (China); Zhang Lirong; Huo Qisheng [State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China); Liu Yunling, E-mail: yunling@jlu.edu.cn [State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)

    2013-01-15

    Two novel anionic indium phosphites, formulated as [H{sub 3}O][In(HPO{sub 3}){sub 2}] (1) and [C{sub 4}H{sub 12}N{sub 2}][In{sub 2}(HPO{sub 3}){sub 3}(C{sub 2}O{sub 4})] (2), were prepared under hydrothermal conditions by using piperazine (PIP) as a structure-directing agent (SDA). Single-crystal X-ray diffraction analysis reveals that compounds 1 and 2 crystallize in the hexagonal space group P6{sub 3}mc (No. 186) and orthorhombic space group Cmcm (No. 63), respectively. Compound 1, constructed from InO{sub 6} octahedra and HPO{sub 3} pseudo-pyramids, exhibits a rare (3,6)-connected layer structure with kgd (Kagome dual) topology. Compound 2, on the other hand, features a 3D phosphite-oxalate hybrid structure with intersecting 8- and 12-MRs channels. From a topological perspective 2 can be regarded as a (3, 5)-connected binodal net with the Schlaefli symbol (4{sup 2}.6)(4{sup 2}.6{sup 5}.8{sup 3}). Highlights: Black-Right-Pointing-Pointer Two novel indium phosphite and indium phosphite-oxalate hybrid compounds are synthesized. Black-Right-Pointing-Pointer (3, 6)-connected layer structure with kgd topology. Black-Right-Pointing-Pointer (3,5)-connected binodal net with the Schlaefli symbol (4{sup 2}.6)(4{sup 2}.6{sup 5}.8{sup 3}).

  2. Anti-AIDS Agents 90. Novel C-28 Modified Bevirimat Analogs as Potent HIV Maturation Inhibitors

    PubMed Central

    Qian, Keduo; Bori, Ibrahim D.; Chen, Chin-Ho; Huang, Li; Lee, Kuo-Hsiung

    2012-01-01

    In a continuing study of bevirimat (2), the anti-HIV-maturation clinical trials agent, 28 new betulinic acid (BA, 1) derivatives were designed and synthesized. Among these compounds, 17, with a C-28 MEM ester moiety, and 22, with a C-28 ethyl hexanoate, increased the anti-HIV replication activity compared with 2 by two-fold, while compounds 40–41 and 48–49, with C-28 piperazine or piperidine amide substitutions, increased the activity by three- to fifteen-fold. The best new compound 41 exhibited an anti-HIV IC50 value of 0.0059 ?M, compared with 0.087 ?M for 2. All of the active compounds showed only anti-maturation effects, as confirmed by TZM-bl assay, in blocking the HIV replication. The results suggest that proper C-28 substitutions can further enhance the anti-maturation activity of 2, without any anti-entry effects. Thus, 41 may serve as a promising new lead for development of anti-AIDS clinical trial candidates. PMID:22978745

  3. Biochemical constituents of a wild strain of Schizophyllum commune isolated from Achanakmar-Amarkantak Biosphere Reserve (ABR), India.

    PubMed

    Tripathi, Arpita Mani; Tiwary, Bhupendra N

    2013-08-01

    A wild strain of Schizophyllum commune (MTCC 9670) isolated from Achanakmar-Amarkantak Biosphere Reserve of Central India was evaluated for the production of bioactive compounds. The chemical constituents of wild and in vitro grown cultures were compared. Under optimized conditions, different organic and aqueous extracts from mycelia and fruiting bodies were used to extract chemical components from the cultures grown in vitro. The gas chromatography combined wih mass spectrometry analysis of extracts identified two phenolic compounds, namely Phenyl benzoate (C13H10O2) and 4-(phenyl methoxy) phenol (C13H12O2) in the ethanolic extract of in vitro grown fruiting bodies and one antibacterial compound Pyrrolo (1, 2-a) piperazine-3, 6-dione (C7H10O2N2) in the methanolic extract of mycelia. High-performance liquid chromatography analysis revealed that the gallic acid and L-ascorbic acid were identifiable antioxidant components in the extracts possessing high free radical scavenging activity. The findings suggest that the wild strain of S. commune may serve as the source of novel bioactive compounds with effective antimicrobial and antioxidant activities. PMID:23475305

  4. Biodegradation of the X-ray contrast agent iopromide and the fluoroquinolone antibiotic ofloxacin by the white rot fungus Trametes versicolor in hospital wastewaters and identification of degradation products.

    PubMed

    Gros, Meritxell; Cruz-Morato, Carles; Marco-Urrea, Ernest; Longrée, Philipp; Singer, Heinz; Sarrà, Montserrat; Hollender, Juliane; Vicent, Teresa; Rodriguez-Mozaz, Sara; Barceló, Damià

    2014-09-01

    This paper describes the degradation of the X-ray contrast agent iopromide (IOP) and the antibiotic ofloxacin (OFLOX) by the white-rot-fungus Trametes versicolor. Batch studies in synthetic medium revealed that between 60 and 80% of IOP and OFLOX were removed when spiked at approximately 12 mg L(-1) and 10 mg L(-1), respectively. A significant number of transformation products (TPs) were identified for both pharmaceuticals, confirming their degradation. IOP TPs were attributed to two principal reactions: (i) sequential deiodination of the aromatic ring and (ii) N-dealkylation of the amide at the hydroxylated side chain of the molecule. On the other hand, OFLOX transformation products were attributed mainly to the oxidation, hydroxylation and cleavage of the piperazine ring. Experiments in 10 L-bioreactor with fungal biomass fluidized by air pulses operated in batch achieved high percentage of degradation of IOP and OFLOX when load with sterile (87% IOP, 98.5% OFLOX) and unsterile (65.4% IOP, 99% OFLOX) hospital wastewater (HWW) at their real concentration (?g L(-1) level). Some of the most relevant IOP and OFLOX TPs identified in synthetic medium were also detected in bioreactor samples. Acute toxicity tests indicated a reduction of the toxicity in the final culture broth from both experiments in synthetic medium and in batch bioreactor. PMID:24867600

  5. The distributional nexus of choroid plexus to cerebrospinal fluid, ependyma and brain: toxicologic/pathologic phenomena, periventricular destabilization, and lesion spread.

    PubMed

    Johanson, Conrad; Stopa, Edward; McMillan, Paul; Roth, Daniel; Funk, Juergen; Krinke, Georg

    2011-01-01

    Bordering the ventricular cerebrospinal fluid (CSF) are epithelial cells of choroid plexus (CP), ependyma and circumventricular organs (CVOs) that contain homeostatic transporters for mediating secretion/reabsorption. The distributional pathway ("nexus") of CP-CSF-ependyma-brain furnishes peptides, hormones, and micronutrients to periventricular regions. In disease/toxicity, this nexus becomes a conduit for infectious and xenobiotic agents. The sleeping sickness trypanosome (a protozoan) disrupts CP and downstream CSF-brain. Piperamide is anti-trypanosomic but distorts CP epithelial ultrastructure by engendering hydropic vacuoles; this reflects phospholipidosis and altered lysosomal metabolism. CP swelling by vacuolation may occlude CSF flow. Toxic drug tools delineate injuries to choroidal compartments: cyclophosphamide (vasculature), methylcellulose (interstitium), and piperazine (epithelium). Structurally perturbed CP allows solutes to penetrate the ventricles. There, CSF-borne pathogens and xenobiotics may permeate the ependyma to harm neurogenic stem cell niches. Amoscanate, an anti-helmintic, potently injures rodent ependyma. Ependymal/brain regions near CP are vulnerable to CSF-borne toxicants; this proximity factor links regional barrier breakdown to nearby periventricular pathology. Diverse diseases (e.g., African sleeping sickness, multiple sclerosis) take early root in choroidal, circumventricular, or perivascular loci. Toxicokinetics informs on pathogen, anti-parasitic agent, and auto-antibody distribution along the CSF nexus. CVOs are susceptible to plasma-borne toxicants/pathogens. Countering the physico-chemical and pathogenic insults to the homeostasis-mediating ventricle-bordering cells sustains brain health and fluid balance. PMID:21189316

  6. Lead-oriented synthesis: Investigation of organolithium-mediated routes to 3-D scaffolds and 3-D shape analysis of a virtual lead-like library.

    PubMed

    Lüthy, Monique; Wheldon, Mary C; Haji-Cheteh, Chehasnah; Atobe, Masakazu; Bond, Paul S; O'Brien, Peter; Hubbard, Roderick E; Fairlamb, Ian J S

    2015-06-01

    Synthetic routes to six 3-D scaffolds containing piperazine, pyrrolidine and piperidine cores have been developed. The synthetic methodology focused on the use of N-Boc ?-lithiation-trapping chemistry. Notably, suitably protected and/or functionalised medicinal chemistry building blocks were synthesised via concise, connective methodology. This represents a rare example of lead-oriented synthesis. A virtual library of 190 compounds was then enumerated from the six scaffolds. Of these, 92 compounds (48%) fit the lead-like criteria of: (i) -1?AlogP?3; (ii) 14?number of heavy atoms?26; (iii) total polar surface area?50Å(2). The 3-D shapes of the 190 compounds were analysed using a triangular plot of normalised principal moments of inertia (PMI). From this, 46 compounds were identified which had lead-like properties and possessed 3-D shapes in under-represented areas of pharmaceutical space. Thus, the PMI analysis of the 190 member virtual library showed that whilst scaffolds which may appear on paper to be 3-D in shape, only 24% of the compounds actually had 3-D structures in the more interesting areas of 3-D drug space. PMID:25936257

  7. Structure-activity relationships of quinolone agents against mycobacteria: effect of structural modifications at the 8 position.

    PubMed Central

    Renau, T E; Gage, J W; Dever, J A; Roland, G E; Joannides, E T; Shapiro, M A; Sanchez, J P; Gracheck, S J; Domagala, J M; Jacobs, M R; Reynolds, R C

    1996-01-01

    A series of quinolones with substitutions at the 8 position has been prepared as part of a study to examine the relationship between structural modifications at this position and activity against mycobacteria. The compounds were prepared by procedures described in the literature and were evaluated for their activities against Mycobacterium fortuitum and Mycobacterium smegmatis. The activities of the compounds against these two organisms were used as a measure of Mycobacterium tuberculosis activity. The results demonstrate that the contribution of the 8 position to antimycobacterial activity was dependent on the substituent at N-1 and was in the order (i) COMe approximately CBr > CCI > CH approximately CF approximately COEt > N > CCF3 when N-1 was cyclopropyl; (ii) N approximately CH > CF > COMe when N-1 was 2,4-difluorophenyl; (iii) N > or = CH when N-1 was tert-butyl; and (iv) N > CH when N-1 was ethyl. In general, derivatives with piperazine substitutions at C-7 were slightly less active against mycobacteria than the analogs with pyrrolidine substitutions, regardless of the pattern of substitution at the 8 position. Several of the best compounds were evaluated for their potential side effects as well as their activities against Mycobacterium aurum, Mycobacterium avium-M. intracellulare, and M. tuberculosis. These agents exhibited biological profiles similar to or better than those of the positive controls ciprofloxacin and sparfloxacin. PMID:8891145

  8. Novel progesterone receptor modulators with gene selective and context-dependent partial agonism.

    PubMed

    Berrodin, Thomas J; Jelinsky, Scott A; Graciani, Nilsa; Butera, John A; Zhang, Zhiming; Nagpal, Sunil; Winneker, Richard C; Yudt, Matthew R

    2009-01-15

    Progesterone receptor (PR) modulators are used in contraception and post-menopausal hormone therapy, and are under clinical development for reproductive disorders such as uterine fibroids and endometriosis. Development of tissue selective PR modulators (SPRMs) with reduced side effects and improved pharmacology represents a large unmet medical need in the area of women's health. One approach to addressing this need is to focus on the two PR isoforms PR-A and PR-B. In vitro and in vivo studies have revealed both distinct as well as overlapping gene regulation and functional responses of the two PR isoforms that suggests that PR-A selective modulators may retain a desired biological profile. We have identified a chemical series of 4-(4-chlorophenyl)-substituted piperazine carbimidothioic acid esters (PCEs) that have partial PR agonist activity and selectively activate some PR-A isoform regulated genes in T47D cells. However, full microarray analysis in these cells does not predict a global isoform selective profile for these compounds, but rather a unique gene-selective profile is observed relative to steroidal progestins. Using multiplexed peptide interaction profiling and co-activator recruitment assays we find that the mechanism of partial agonism is only partly defined by the ability to recruit known co-activators or peptides but also depends on the cell and promoter context of the gene under investigation. The data demonstrate global consequences of mechanistic and functional differences that can lead to selective biological responses of novel steroid receptor modulators. PMID:19013437

  9. The isolation and partial characterization of ribonuclease A from Bison bison

    PubMed Central

    Stewart, Gordon R.; Stevenson, Kenneth J.

    1973-01-01

    1. Bison ribonuclease was isolated from pancreas glands of Bison bison by acid extraction, (NH4)2SO4 fractionation, affinity chromatography on Sepharose–5?-(4-aminophenylphosphoryl)uridine 2?,3?-phosphate and ion-exchange chromatography on Bio-Rex-70. 2. The selectivity of the affinity column towards bison ribonuclease in heterogeneous protein solutions was greatly improved by employing piperazine buffers at pH5.3, which decreased non-specific interactions of other proteins. Rapid desorption from the affinity column was obtained with sodium phosphate buffer (pH3). 3. Bison ribonuclease has a total amino acid content very similar to ox ribonuclease. Inactivation of bison ribonuclease with iodoacetic acid leads to the formation of 0.62 residues of ?-carboxymethylhistidine and 0.36 residues of ?-carboxymethylhistidine. The amino acid composition of peptides isolated from diagonal peptide `maps' and also of peptides isolated after pH1.6 and 2.4 two-dimensional high-voltage electrophoresis of a digest of bison ribonuclease labelled with pyridoxal 5-phosphate indicates that there is complete homology between ox and bison ribonucleases. 4. The Schiff-base attachment site of pyridoxal 5-phosphate was identified as lysine-41 by NaBH4 reduction followed by peptide isolation. PMID:4772270

  10. Antiproliferation activity of a small molecule repressor of liver receptor homolog 1.

    PubMed

    Corzo, Cesar A; Mari, Yelenis; Chang, Mi Ra; Khan, Tanya; Kuruvilla, Dana; Nuhant, Philippe; Kumar, Naresh; West, Graham M; Duckett, Derek R; Roush, William R; Griffin, Patrick R

    2015-02-01

    The orphan nuclear receptor liver receptor homolog 1 (LRH-1; NR5A2) is a potent regulator of cholesterol metabolism and bile acid homeostasis. Recently, LRH-1 has been shown to play an important role in intestinal inflammation and in the progression of estrogen receptor positive and negative breast cancers and pancreatic cancer. Structural studies have revealed that LRH-1 can bind phospholipids and the dietary phospholipid dilauroylphosphatidylcholine activates LRH-1 activity in rodents. Here we characterize the activity of a novel synthetic nonphospholipid small molecule repressor of LRH-1, SR1848 (6-[4-(3-chlorophenyl)piperazin-1-yl]-3-cyclohexyl-1H-pyrimidine-2,4-dione). In cotransfection studies, SR1848 reduced LRH-1-dependent expression of a reporter gene and in cells that endogenously express LRH-1 dose dependently reduced the expression of cyclin-D1 and -E1, resulting in inhibition of cell proliferation. The cellular effects of SR1848 treatment are recapitulated after transfection of cells with small-interfering RNA targeting LRH-1. Immunocytochemistry analysis shows that SR1848 induces rapid translocation of nuclear LRH-1 to the cytoplasm. Combined, these results suggest that SR1848 is a functional repressor of LRH-1 that impacts expression of genes involved in proliferation in LRH-1-expressing cancers. Thus, SR1848 represents a novel chemical scaffold for the development of therapies targeting malignancies driven by LRH-1. PMID:25473120

  11. Degradation of polyamide nanofiltration and reverse osmosis membranes by hypochlorite.

    PubMed

    Do, Van Thanh; Tang, Chuyang Y; Reinhard, Martin; Leckie, James O

    2012-01-17

    The degradation of polyamide (PA) nanofiltration and reverse osmosis membranes by chlorine needs to be understood in order to develop chlorine-resistant membranes. Coated and uncoated fully aromatic (FA) and piperazine (PIP) semi-aromatic PA membranes were treated with hypochlorite solution and analyzed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR). XPS results showed that in chlorine treated FA PA membranes the ratio of bound chlorine to surface nitrogen was 1:1 whereas it was only 1:6 in the case of PIP PA membranes. Surface oxygen of uncoated FA and PIP membranes increased with increasing hypochlorite concentration whereas it decreased for coated FA membranes. High resolution XPS data support that chlorination increased the number of carboxylic groups on the PA surface, which appear to form by hydrolysis of the amide bonds (C(O)-N). FTIR data indicated the disappearance of the amide II band (1541 cm(-1)) and aromatic amide peak (1609 cm(-1)) in both coated and uncoated chlorinated FA membranes, consistent with the N-chlorination suggested by the XPS results. Furthermore, the surface charge of chlorinated membranes at low pH (<6) became negative, consistent with amide-nitrogen chlorination. Chlorination appeared to both increase and decrease membrane hydrophobicity depending on chlorination exposure conditions, which implied that N-chlorination and hydrolysis may be competing processes. The effects of property changes on the membrane performance were also observed for NF90, BW30, and NF270 membranes. PMID:22221176

  12. Diclofenac salts, part 7: are the pharmaceutical salts with aliphatic amines stable?

    PubMed

    Fini, Adamo; Cavallari, Cristina; Bassini, Glenda; Ospitali, Francesca; Morigi, Rita

    2012-09-01

    Eight cyclic aliphatic amines, pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz), and the N-hydroxyethyl (HE) analogues, were employed to prepare a salt with acidic diclofenac (D). These salts were examined by thermal [differential scanning calorimetry (DSC), thermogravimetric analysis, and hot-stage microscopy (HSM)] and spectroscopic [Fourier transform infrared (FTIR), Raman, (1) H NMR, and ultraviolet] analysis. The results show the thermal instability of these salts: the thermal dissociation leaves the starting acidic D, evidenced by the FTIR and Raman spectra inside the molten mass of the salts with M and HEM. The nature of the salt with Pz (1:1 or 1:2) and HEPy (anhydrous or hydrate polymorph), but not for the salt with HEPz and Py, depends on the polarity of the solvent used for the preparation of the salt. Incomplete dehydration of the hydrate Py and Pz salts progressively modifies the thermogram profiles and originates false information. Melting of the salts with Pp, M, and HEM could be demonstrated by HSM, but not with DSC. The difficulty of providing a description of these salts in a simple way originates doubts on the utility of a wide application of aliphatic amines to prepare pharmaceutical salts with D, whose solubility in water does not significantly differ from that of the common sodium D. PMID:22234897

  13. Free radical scavenging, antidiarrheal and anthelmintic activity of Pistia stratiotes L. extracts and its phytochemical analysis.

    PubMed

    Bin Karim, Mohammed Faisal; Imam, Hasan; Sarker, Md Moklesur-Rahman; Uddin, Nizam; Hasan, Nahid; Paul, Nirmala; Haque, Tahmina

    2015-05-01

    In this phyto-pharmacological screening of Pistia stratiotes L leaf and root extracts each separately in two different solvents demonstrated its potential medicinal value. Apparent antioxidant value is demonstrated by DPPH, Nitric oxide scavenging and Ferric ion reducing method. Additionally, total flavonoid and phenolic compounds were measured. The leaf methanolic extract scavenged both nitric oxide (NO) and DPPH radical with a dose dependent manner. But the pet ether fraction of root was found to have highest efficacy in Fe(3±) reducing power assay. Flavonoid was found to contain highest in the pet ether fraction of root (411.35mg/g) in terms of quercetin equivalent, similarly highest amount (34.96mg/g) of total phenolic compounds (assayed as gallic acid equivalents) were found to contain in the same fraction. The methanolic fractions appeared less cytotoxic compared to pet ether extracts. The plant extracts caused a dose dependent decrease in faecal droppings in both castor oil and magnesium sulphate induced diarrhea, where as leaf extracts in each solvent appeared most effective. Also, the plant extracts showed anthelmintic activity in earthworm by inducing paralysis and death in a dose dependent manner. At highest doses (50 mg/ml) all fractions were almost effective as the positive control piperazine citrate (10 mg/ml). Thus, besides this cytotoxic effect it's traditional claim for therapeutic use can never be overlooked. PMID:26004725

  14. Do imipramine and dihydroergosine possess two components - one stimulating 5-HT sub 1 and the other inhibiting 5-HT sub 2 receptors

    SciTech Connect

    Pericic, D.; Mueck-Seler, D. (Rudjer Boskovic Institute, Zagreb (Yugoslavia))

    1990-01-01

    The mechanisms by which imipramine and dihydroergosine stimulate the 5-HT syndrome in rats and inhibit the head-twitch response in rats and mice were studied. Imipramine- and dihydroergosine-included stimulation of the 5-HT syndrome was inhibited stereoselectively by propranolol, a high affinity ligand for 5-HT{sub 1} receptor sites, but not by ritanserin, a specific 5-HT{sub 2} receptor antagonist. (-) -Propranolol potentiated the inhibitory effect of imipramine, but not of dihydroergosine on the head-twitch response, while ritanserin was without effect. As expected, 8-OH-DPAT, a selective 5-HT{sub 1A} receptor agonist, stimulated, and 5-HT{sub 1B} agonists CGS 12066B and 1-(trifluoromethylphenyl) piperazine (TFMPP) failed to stimulate the 5-HT syndrome induced in rats by pargyline and 5-HTP administration. A higher dose of ritanserin inhibited the syndrome. While 8-OH-DPAT alone produced all behavioral components of the 5-HT syndrome, dihydroergosine or imipramine alone even at very high doses never produced tremor or a more intensive forepaw padding as seen when these drugs were given in combination with pargyline and 5-HTP. A single administration of (-)-propranolol also inhibited the head-twitch response. This effect lasted in mice longer that after ritanserin administration. In in vitro experiments dihydroergosine expressed approximately twenty-fold higher affinity for {sup 3}H-ketanserin binding sites than imipramine.

  15. Improved antifouling properties of polyamide nanofiltration membranes by reducing the density of surface carboxyl groups.

    PubMed

    Mo, Yinghui; Tiraferri, Alberto; Yip, Ngai Yin; Adout, Atar; Huang, Xia; Elimelech, Menachem

    2012-12-18

    Carboxyls are inherent functional groups of thin-film composite polyamide nanofiltration (NF) membranes, which may play a role in membrane performance and fouling. Their surface presence is attributed to incomplete reaction of acyl chloride monomers during the membrane active layer synthesis by interfacial polymerization. In order to unravel the effect of carboxyl group density on organic fouling, NF membranes were fabricated by reacting piperazine (PIP) with either isophthaloyl chloride (IPC) or the more commonly used trimesoyl chloride (TMC). Fouling experiments were conducted with alginate as a model hydrophilic organic foulant in a solution, simulating the composition of municipal secondary effluent. Improved antifouling properties were observed for the IPC membrane, which exhibited lower flux decline (40%) and significantly greater fouling reversibility or cleaning efficiency (74%) than the TMC membrane (51% flux decline and 40% cleaning efficiency). Surface characterization revealed that there was a substantial difference in the density of surface carboxyl groups between the IPC and TMC membranes, while other surface properties were comparable. The role of carboxyl groups was elucidated by measurements of foulant-surface intermolecular forces by atomic force microscopy, which showed lower adhesion forces and rupture distances for the IPC membrane compared to TMC membranes in the presence of calcium ions in solution. Our results demonstrated that a decrease in surface carboxyl group density of polyamide membranes fabricated with IPC monomers can prevent calcium bridging with alginate and, thus, improve membrane antifouling properties. PMID:23205860

  16. Virtual screening-based discovery and mechanistic characterization of the acylthiourea MRT-10 family as smoothened antagonists.

    PubMed

    Manetti, Fabrizio; Faure, Helene; Roudaut, Hermine; Gorojankina, Tatiana; Traiffort, Elisabeth; Schoenfelder, Angele; Mann, Andre; Solinas, Antonio; Taddei, Maurizio; Ruat, Martial

    2010-10-01

    The seven-transmembrane receptor Smoothened (Smo) is the major component involved in signal transduction of the Hedgehog (Hh) morphogens. Smo inhibitors represent a promising alternative for the treatment of several types of cancers linked to abnormal Hh signaling. Here, on the basis of experimental data, we generated and validated a pharmacophoric model for Smo inhibitors constituted by three hydrogen bond acceptor groups and three hydrophobic regions. We used this model for the virtual screening of a library of commercially available compounds. Visual and structural criteria allowed the selection of 20 top scoring ligands, and an acylthiourea, N-(3-benzamidophenylcarbamothioyl)-3,4,5-trimethoxybenzamide (MRT-10), was identified and characterized as a Smo antagonist. The corresponding acylurea, N-(3-benzamidophenylcarbamoyl)-3,4,5-trimethoxybenzamide (MRT-14), was synthesized and shown to display, in various Hh assays, an inhibitory potency comparable to or greater than that of reference Smo antagonists cyclopamine and N-((3S,5S)-1-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(piperazine-1-carbonyl)pyrrolidin-3-yl)-N-(3-methoxybenzyl)-3,3-dimethylbutanamide (Cur61414). Focused virtual screening of the same library further identified five additional related antagonists. MRT-10 and MRT-14 constitute the first members of novel families of Smo antagonists. The described virtual screening approach is aimed at identifying novel modulators of Smo and of other G-protein coupled receptors. PMID:20664000

  17. Generation of Phosphorescent Triplet States via Photoinduced Electron Transfer: Energy and Electron Transfer Dynamics in Pt Porphyrin-Rhodamine B Dyads

    PubMed Central

    Mani, Tomoyasu; Niedzwiedzki, Dariusz M.; Vinogradov, Sergei A.

    2012-01-01

    Control over generation and dynamics of excited electronic states is fundamental to their utilization in all areas of technology. We present the first example of multichromophoric systems in which emissive triplet states are generated via a pathway involving photoinduced electron transfer (ET), as opposed to local intrachromophoric processes. In model dyads, PtP-Phn-pRhB+ (1-3, n=1-3), comprising platinum(II) meso-tetraarylporphyrin (PtP) and rhodamine B piperazine derivative (pRhB+), linked by oligo-p-phenylene bridges (Phn), upon selective excitation of pRhB+ at a frequency below that of the lowest allowed transition of PtP, room-temperature T1?S0 phosphorescence of PtP was observed. The pathway leading to the emissive PtP triplet state includes excitation of pRhB+, ET with formation of the singlet radical pair, intersystem crossing within that pair and subsequent radical recombination. Due to the close proximity of the triplet energy levels of PtP and pRhB+, reversible triplet-triplet (TT) energy transfer between these states was observed in dyads 1 and 2. As a result, the phosphorescence of PtP was extended in time by the long decay of the pRhB+ triplet. Observation of ET and TT in the same series of molecules enabled direct comparison of the distance attenuation factors ? between these two closely related processes. PMID:22400988

  18. Spectroscopic investigation (FT-IR, FT-Raman and SERS), vibrational assignments, HOMO-LUMO analysis and molecular docking study of Opipramol.

    PubMed

    Mary, Y Sheena; Panicker, C Yohannan; Kavitha, C N; Yathirajan, H S; Siddegowda, M S; Cruz, Sandra M A; Nogueira, Helena I S; Al-Saadi, Abdulaziz A; Van Alsenoy, Christian; War, Javeed Ahmad

    2015-02-25

    FT-IR and FT-Raman spectra of Opipramol were recorded and analyzed. SERS spectrum was recorded in silver colloid. The vibrational wave numbers were computed using DFT quantum chemical calculations. The data obtained from wave number calculations are used to assign vibrational bands obtained in infrared and Raman spectra as well as in SERS of the studied molecule. Potential energy distribution was done using GAR2PED program. The geometrical parameters (DFT) of the title compound are in agreement with the XRD results. The presence of CH2 stretching modes in the SERS spectrum indicates the close of piperazine ring with the metal surface and the interaction of the silver surface with this moiety. NBO analysis, HOMO-LUMO, first hyperpolarizability and molecular electrostatic potential results are also reported. The inhibitor Opipramol forms a stable complex with P4502C9 as is evident from the ligand-receptor interactions and a -9.0 kcal/mol docking score and may be an effective P4502C9 inhibitor if further biological explorations are carried out. PMID:25240828

  19. Spectroscopic investigation (FT-IR, FT-Raman and SERS), vibrational assignments, HOMO-LUMO analysis and molecular docking study of Opipramol

    NASA Astrophysics Data System (ADS)

    Mary, Y. Sheena; Panicker, C. Yohannan; Kavitha, C. N.; Yathirajan, H. S.; Siddegowda, M. S.; Cruz, Sandra M. A.; Nogueira, Helena I. S.; Al-Saadi, Abdulaziz A.; Van Alsenoy, Christian; War, Javeed Ahmad

    2015-02-01

    FT-IR and FT-Raman spectra of Opipramol were recorded and analyzed. SERS spectrum was recorded in silver colloid. The vibrational wave numbers were computed using DFT quantum chemical calculations. The data obtained from wave number calculations are used to assign vibrational bands obtained in infrared and Raman spectra as well as in SERS of the studied molecule. Potential energy distribution was done using GAR2PED program. The geometrical parameters (DFT) of the title compound are in agreement with the XRD results. The presence of CH2 stretching modes in the SERS spectrum indicates the close of piperazine ring with the metal surface and the interaction of the silver surface with this moiety. NBO analysis, HOMO-LUMO, first hyperpolarizability and molecular electrostatic potential results are also reported. The inhibitor Opipramol forms a stable complex with P4502C9 as is evident from the ligand-receptor interactions and a -9.0 kcal/mol docking score and may be an effective P4502C9 inhibitor if further biological explorations are carried out.

  20. WAY 100,135 and (-)-tertatolol act as antagonists at both 5-HT1A autoreceptors and postsynaptic 5-HT1A receptors in vivo.

    PubMed

    Lejeune, F; Rivet, J M; Gobert, A; Canton, H; Millan, M J

    1993-08-24

    In binding studies, WAY 100,135 (N-tertiobutyl-3-[4-(2-methoxyphenyl)-piperazinyl]-2-phenylpropana mide) and (-)-tertatolol showed affinities (Ki) of 29 nM and 10 nM, respectively, at 5-HT1A receptors. In vivo, they both dose dependently blocked the flat-body posture and corticosterone secretion provoked by an action of the 5-HT1A receptor agonist, S 14671 (1-[2-(2-thenoyl-amino)ethyl]-4-[1-(7- methoxynaphtyl)]piperazine), at postsynaptic 5-HT1A receptors. Alone, they exerted little effect. The firing rate of dorsal raphe neurones, which bear inhibitory 5-HT1A autoreceptors, was reduced by S 14671 whereas it was not affected by WAY 100,135 and was increased by (-)-tertatolol. Both WAY 100,135 and (-)-tertatolol blocked the ability of S 14671 to inhibit raphe firing. In conclusion, these data demonstrate that WAY 100,135 and (-)-tertatolol behave as antagonists at both 5-HT1A autoreceptors and postsynaptic 5-HT1A receptors in vivo. PMID:8243546

  1. Enrofloxacinium oxalate

    PubMed Central

    Yamuna, Thammarse S.; Kaur, Manpreet; Anderson, Brian J.; Jasinski, Jerry P.; Yathirajan, H. S.

    2014-01-01

    The title salt, 2C19H23FN3O3 +·C2O4 2? {systematic name: bis-[4-(3-carb­oxy-1-cyclo­propyl-6-fluoro-4-oxo-1,4-di­hydro­quino­lin-7-yl)-1-ethyl­piperazin-1-ium] oxalate}, crystallizes with two independent monocations (A and B) and an oxalate dianion (C) in the asymmetric unit. The piperazinium ring in both the cations adopts a slightly disordered chair conformation. The dihedral angles between the mean planes of the cyclo­propyl ring and the 10-membered quinoline ring are 50.6?(5)° (A) and 62.2?(5)° (B). In each of the cations, a single O—H?O intra­molecular hydrogen bond is observed. In the crystal, the oxalate anions inter­act with the cations through N—H?O hydrogen bonds and weak C—H?O inter­actions, forming R 2 2(8) graph-set ring motifs. Weak C—H?F inter­actions along with further C—H?O inter­actions are observed between the cations, forming zigzag chains along [001]. In addition, ?–? stacking inter­actions are observed with centroid–centroid distances of 3.5089?(13), 3.5583?(13), 3.7900?(13) and 3.7991?(13)?Å. PMID:24764910

  2. The Pyrolytic Profile of Lyophilized and Deep-Frozen Compact Part of the Human Bone

    PubMed Central

    Lodowska, Jolanta; Wolny, Daniel; Kurkiewicz, S?awomir; W?glarz, Ludmi?a

    2012-01-01

    Background. Bone grafts are used in the treatment of nonunion of fractures, bone tumors and in arthroplasty. Tissues preserved by lyophilization or deep freezing are used as implants nowadays. Lyophilized grafts are utilized in the therapy of birth defects and bone benign tumors, while deep-frozen ones are applied in orthopedics. The aim of the study was to compare the pyrolytic pattern, as an indirect means of the analysis of organic composition of deep-frozen and lyophilized compact part of the human bone. Methods. Samples of preserved bone tissue were subjected to thermolysis and tetrahydroammonium-hydroxide- (TMAH-) associated thermochemolysis coupled with gas chromatography and mass spectrometry (Py-GC/MS). Results. Derivatives of benzene, pyridine, pyrrole, phenol, sulfur compounds, nitriles, saturated and unsaturated aliphatic hydrocarbons, and fatty acids (C12–C20) were identified in the pyrolytic pattern. The pyrolyzates were the most abundant in derivatives of pyrrole and nitriles originated from proteins. The predominant product in pyrolytic pattern of the investigated bone was pyrrolo[1,2-?]piperazine-3,6-dione derived from collagen. The content of this compound significantly differentiated the lyophilized graft from the deep-frozen one. Oleic and palmitic acid were predominant among fatty acids of the investigated samples. The deep-frozen implants were characterized by higher percentage of long-chain fatty acids than lyophilized grafts. PMID:22619606

  3. S-15176 and its methylated derivative suppress the CsA-insensitive mitochondrial permeability transition and subsequent cytochrome c release induced by silver ion, and show weak protonophoric activity.

    PubMed

    Kawashima, Satoshi; Yamamoto, Takenori; Horiuchi, Yuka; Fujiwara, Kengo; Gouda, Shunichi; Yoshimura, Yuya; Yamamoto, Atsushi; Inotani, Yuki; Yamashita, Kikuji; Kitamura, Seiichiro; Terada, Hiroshi; Kanematsu, Makoto; Shishido, Kozo; Shinohara, Yasuo

    2011-12-01

    A recent report has described that S-15176 (N-[(3,5-di-tert-butyl-4-hydroxy-1-thiophenyl)]-3-propyl-N'-(2,3,4-trimethoxybenzyl) piperazine), an anti-ischemic agent, inhibits the mitochondrial permeability transition (PT) induced by not only Ca(2+) and inorganic phosphate, but also by tert-butylhydroperoxide or phenylarsine oxide [Morin et al. (Biochem Pharmacol 72:911-918, 2006)]. In the present study, we tested the effects of S-15176 on the PT induced by Ag(+), PT of which is not suppressed by cyclosporin A or oligomycin. S-15176 was effective in suppressing the PT and the subsequent cytochrome c release induced by Ag(+), and hence, it was concluded to be a more universal PT inhibitor than cyclosporin A or oligomycin. In addition to the PT-suppression activity, S-15176 also showed weak protonophoric activity. Thus, we further tested to investigate whether the hydroxyl group of S-15176 was involved in its PT-suppression or weak protonophoric activities. The methylated derivative of S-15176 also showed both PT suppression and weak protonophoric activities; hence, the hydroxyl group of S-15176 was concluded not to be involved in these activities. PMID:21688046

  4. Buffering limits plasma HCO3- dehydration when red blood cell anion exchange is inhibited.

    PubMed

    Gilmour, K M; Desforges, P R; Perry, S F

    2004-05-20

    Theory suggests that HCO3- dehydration in the plasma of rainbow trout is limited by both the absence of carbonic anhydrase (CA) activity and the low non-bicarbonate buffer capacity of the plasma (betaplasma). The potential for betaplasma to limit plasma HCO3- dehydration was assessed in rainbow trout in which HCO3- dehydration via the red blood cell (RBC) was inhibited using the anion exchange blocker 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS). DIDS administration reduced the rate of RBC HCO3- dehydration by 68-80% for at least 6h, resulting in the elevation of arterial CO2 tension (PaCO2) by 3.07 +/- 0.45 Torr (N = 6). Addition of bovine CA to the circulation of DIDS-treated trout caused PaCO2 to decrease significantly. This effect was increased significantly in rainbow trout in which betaplasma was elevated experimentally by intravascular injection of N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid] (HEPES), supporting the hypothesis that CA-catalysed HCO3- dehydration in the plasma of rainbow trout is limited by proton availability. PMID:15134665

  5. [Comparative studies of the nitrosation behavior of drugs by constant pH value and under simulated stomach conditions].

    PubMed

    Ziebarth, D

    1982-01-01

    The nitrosation behaviour of 60 orally administered drugs used in the GDR have been investigated. Only those pharmaceuticals were selected whose active agents are assessed as being nitrosatable by their chemical structures. Amounts of active components and nitrite, dissolved in the gastric juice, did not exceed the concentrations permissible for human stomachs in vivo. After one-hour incubation at pH 2.0 and 37 degrees C ten drugs (Aminophenazone, Ampicilline, Clomipramine, Desipramine, Ethambutole, Imipramine, Noramidopyrinmethansulfonate, Oxacilline, Phenoxymethylpenicilline, Piperazine) proved to be nitrosatable using a colorimetric measuring method. Two of the N-nitroso compounds have been identified as known carcinogens. Structure analysis of the remaining ones is not yet finished. Results still more conforming to in vivo conditions have been obtained for all ten nitrosatable drugs by means of a model system simulating the conditions of the human stomach. The pH changes attending the shifts of pH occurring in the course of the digestive process have a distinct effect on the nitrosation reactions. It is only on such measurements of drug nitrosation that decisions on oral application, calculation of the burdening of the organism by N-nitroso compounds, or estimation of risk should be based. PMID:7159182

  6. Reactivity of chemical respiratory allergens in the Peroxidase Peptide Reactivity Assay.

    PubMed

    Lalko, J F; Dearman, R J; Gerberick, G F; Troutman, J A; Api, A M; Kimber, I

    2013-03-01

    Sensitizing chemicals are commonly associated primarily with either skin or respiratory sensitization. In the Direct Peptide Reactivity Assay (DPRA), when compared with skin sensitizers, respiratory allergens have been demonstrated to selectively react with lysine rather than cysteine. The Peroxidase Peptide Reactivity Assay (PPRA) has been developed as a refinement to the DPRA. The PPRA incorporates dose-response analyses, mass spectroscopy for peptide detection and a horseradish peroxidase-hydrogen peroxide enzymatic system, increasing the potential to identify pro-haptens. In the investigations reported here, the PPRA was evaluated to determine whether it provides advantages for the identification of respiratory allergens. Twenty respiratory sensitizers, including five predicted to be pre-/pro-haptens were evaluated. The PPRA performed similarly to the DPRA with respect to identifying inherently reactive respiratory sensitizers. However, three respiratory sensitizers predicted to be pre-/pro-haptens (chlorhexidine, ethylenediamine and piperazine) were non-reactive and the general selectivity of the respiratory allergens for lysine was lost in the PPRA. Overall, the data indicate that the PPRA does not provide an advantage over the DPRA for discriminating allergens as either contact or respiratory sensitizers. Nevertheless, the PPRA provides a number of refinements to the DPRA that allow for an enhanced characterization of reactivity for both classes of chemical allergens. PMID:23137732

  7. SAR-studies on the importance of aromatic ring topologies in search for selective 5-HT(7) receptor ligands among phenylpiperazine hydantoin derivatives.

    PubMed

    Handzlik, Jadwiga; Bojarski, Andrzej J; Sata?a, Grzegorz; Kubacka, Monika; Sadek, Bassem; Ashoor, Abrar; Siwek, Agata; Wi?cek, Ma?gorzata; Kucwaj, Katarzyna; Filipek, Barbara; Kie?-Kononowicz, Katarzyna

    2014-05-01

    The current study is focused on newly developed phenylpiperazine derivatives of aromatic methylhydantoin differing in mutual positions of methyl and phenyl moieties. The new compounds were synthesized using Bucherer-Bergs reaction, two-phase alkylation, Mitsunobu reaction and/or an alkylation under microwave irradiation. The compounds developed were assessed on their affinity for serotoninergic receptors 5-HT1A, 5-HT6, 5-HT7 and ?1-ARs in radioligand binding assays. Selected compounds were tested on their inhibitory effect at human 5-HT3A expressed in Xenopus Oocytes as well as on their activity at ?1-adrenoceptor subtypes in functional and electrophysiological bioassays, respectively. Most of investigated compounds exhibited affinities for ?1-ARs, 5-HT1A, 5-HT7 (Ki ? 0.8-353 nM) significantly higher than those for 5-HT6 receptors. Very weak inhibitory effect at 5-HT3A accompanied with high activity at ?1D-AR subtypes were observed for selected representative compounds. Among the current series, particularly 5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-5-methylimidazolidine-2,4-dione hydrochloride (25a) displayed the highest 5-HT7 affinity with Ki = 3 nM and selectivity with 40-3600 fold towards 5-HT1A, 5-HT6, and ?1-ARs. PMID:24691057

  8. Lanthanide-organic frameworks constructed from multi-functional ligands: Syntheses, structures, near-infrared and visible photoluminescence properties

    SciTech Connect

    Li Xinfa [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100039 (China); Xie Zailai; Lin Jingxiang [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China); Cao Rong, E-mail: rcao@fjirsm.ac.c [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China)

    2009-08-15

    A series of multi-functional ligands supported lanthanide-organic frameworks, formulated as [Ln(HL{sub 1})(H{sub 2}L{sub 2}){sub 0.5}(H{sub 4}L{sub 2}){sub 0.5}(H{sub 2}O)].(H{sub 2}O){sub 1.5}.{l_brace}Ln=La (1), Pr (2), Nd (3), Sm (4), Eu (5); H{sub 3}L{sub 1}=5-Sulfosaclicylic acid; H{sub 4}L{sub 2}=N,N'-piperazine (bis-methylene phosphonic acid){r_brace}, have been synthesized by hydrothermal reactions. Single crystal X-ray diffractions and powder XRD patterns confirm they are isostructural. They feature 3D framework structures based on extension of a 'zigzag' inorganic chain by organic linkers. Moreover, the photoluminescence properties of 5 and 3 have been investigated, and they show strong solid-state emissions in the visible and near-infrared (IR) regions at room temperature. - Graphical abstract: Five multi-functional ligands supported 3D lanthanide-organic frameworks have been synthesized and structurally characterized. Compounds 5 and 3 displayed strong solid-state emissions in the visible and near-infrared region at room temperature.

  9. Synthesis, structure-property relationships and pharmacokinetic evaluation of ethyl 6-aminonicotinate sulfonylureas as antagonists of the P2Y?? receptor.

    PubMed

    Bach, Peter; Boström, Jonas; Brickmann, Kay; van Giezen, J J J; Groneberg, Robert D; Harvey, Darren M; O'Sullivan, Michael; Zetterberg, Fredrik

    2013-07-01

    The present paper describes the development of a new series of P2Y12 receptor antagonists based on our previously reported piperazinyl urea series 1 (IC50 binding affinity = 0.33 ?M, aq solubility <0.1 ?M, microsomal CLint (HLM) ?300 ?M/min/mg). By replacement of the urea functionality with a sulfonylurea group we observed increased affinity along with improved stability and solubility as exemplified by 47 (IC50 binding affinity = 0.042 ?M, aq solubility = 90 ?M, microsomal CLint (HLM) = 70 ?M/min/mg). Further improvements in affinity and metabolic stability were achieved by replacing the central piperazine ring with a 3-aminoazetidine as exemplified by 3 (IC50 binding affinity = 0.0062 ?M, aq solubility = 83 ?M, microsomal CLint (HLM) = 28 ?M/min/mg). The improved affinity observed in the in vitro binding assay also translated to the potency observed in the WPA aggregation assay (47: 19 nM and 3: 9.5 nM) and the observed in vitro ADME properties translates to the in vivo PK properties observed in rat. In addition, we found that the chemical stability of the sulfonylureas during prolonged storage in solution was related to the sulfonyl urea linker and depended on the type of solvent and the substitution pattern of the sulfonyl urea functionality. PMID:23747805

  10. Raman spectra of nitrogen-containing organic compounds obtained in high altitude sites using a portable spectrometer: Possible application for remote robotic Titan studies

    NASA Astrophysics Data System (ADS)

    Jehlicka, Jan; Culka, Adam; Edwards, Howell G. M.

    2010-04-01

    Well-resolved Raman spectra of examples of nitrogen-containing compounds were detected using a portable Raman instrument (Ahura First Defender XL) outdoors at a low temperature of -15 °C at an altitude of 2860 m (Pitztall, Austria). The portable Raman spectrometer tested here is equipped with a 785 nm diode laser and fixed frontal probe. Solid forms of formamide, urea, 3-methylpyridine, aniline, indene, 1-(2-aminoethyl)piperazine, benzofuran and indoline were detected unambiguously under field high-mountain conditions. The main Raman features (strong, medium and partially weak bands) were observed at their correct wavenumber positions (spectral resolution 7-10 cm -1) in the range 200-2000 cm -1. The results obtained demonstrate the possibility of applying a miniaturised Raman spectrometer as key instrument for investigating the presence of nitrogen-containing organic compounds and biomolecules under low temperature field conditions. Within the payload designed by ESA and NASA for future missions focusing not only on Mars, Raman spectroscopy will be an important non-destructive analytical tool for the in-situ identification of both organic and inorganic compounds relevant to life detection on planetary surfaces or near sub-surfaces.

  11. Biotransformation of fluoroquinolone antibiotics by ligninolytic fungi - Metabolites, enzymes and residual antibacterial activity.

    PubMed

    ?van?arová, Monika; Moeder, Monika; Filipová, Alena; Cajthaml, Tomáš

    2015-10-01

    A group of white rot fungi (Irpex lacteus, Panus tigrinus, Dichomitus squalens, Trametes versicolor and Pleurotus ostreatus) was investigated for the biodegradation of norfloxacin (NOR), ofloxacin (OF) and ciprofloxacin (CIP). The selected fluoroquinolones were readily degraded almost completely by I. lacteus and T. versicolor within 10 and 14d of incubation in liquid medium, respectively. The biodegradation products were identified by liquid chromatography-mass spectrometry. The analyses indicated that the fungi use similar mechanisms to degrade structurally related antibiotics. The piperazine ring of the molecules is preferably attacked via either substitution or/and decomposition. In addition to the degradation efficiency, attention was devoted to the residual antibiotic activities estimated using Gram-positive and Gram-negative bacteria. Only I. lacteus was able to remove the antibiotic activity during the course of the degradation of NOR and OF. The product-effect correlations evaluated by Principal Component Analysis (PCA) enabled elucidation of the participation of the individual metabolites in the residual antibacterial activity. Most of the metabolites correlated with the antibacterial activity, explaining the rather high residual activity remaining after the biodegradation. PCA of ligninolytic enzyme activities indicated that manganese peroxidase might participate in the degradation. PMID:25592459

  12. Biologically active and thermally stable polymeric Schiff base and its metal polychelates: Their synthesis and spectral aspects.

    PubMed

    Rasool, Raza; Hasnain, Sumaiya

    2015-09-01

    New metal polychelates of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) obtained by the interaction of metal acetates with polymeric Schiff base containing formaldehyde and piperazine, have been investigated. Structural and spectroscopic properties have been evaluated by elemental analysis, FT-IR and (1)H-NMR. Geometry of the chelated polymers was confirmed by magnetic susceptibility measurements, UV-Visible spectroscopy and Electron Spin Resonance. The molecular weight of the polymer was determined by gel permeation chromatography (GPC). Thermogravimetric analysis indicated that metal polychelates were more thermally stable than their corresponding ligand. All compounds were screened for their antimicrobial activities against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, (bacteria) and Candida albicans, Microsporum canis, Cryptococcus neoformans (fungi) by agar well diffusion method. Interestingly, the polymeric Schiff base was found to be antimicrobial in nature but less effective as compared to the metal polychelates. On the basis of thermal and antimicrobial behavior, these polymers hold potential applications as thermally resistant antimicrobial and antifouling coating materials as well as antimicrobial packaging materials. PMID:25955762

  13. Original approach to the construction of macrocyclic nitrogen heterocycles by means of complex palladium catalysts

    SciTech Connect

    Fakhretdinov, R.N.; Turchin, A.A.; Dzhemilev, U.M.

    1987-09-20

    The authors established for the first time that the reaction of ethylene imine with butadiene (1:2.5) in the presence of the Pd(acac)/sub 2/-Ph/sub 3/P-AlEt/sub 3/-CF/sub 3/CO/sub 2/H (1:3:4:5) catalyst in methanol (100/sup 0/C, 6 h) leads to the formation of N,N'-bis(2,7-octadienyl)piperazine (I), N,N',N''-tris(2,7-octadienyl)perhydro-1,4,7-triazacyclononane (II), and N,N',N'',N'''-tetrakis-(2,7-octadienyl)perhydro-1,4,7,10-tetraazacyclododecane (III) in a (I):(II-III) ratio of 13:87 and with an overall yield of 64%. In addition to compounds (I-III), the authors a 34% yield of N,N-bis(2,7-octadienyl)ethanolamine methyl ether. The mass spectra were obtained on a MX-1320 instrument at 70 and 12 eV. The PMR spectra were recorded on a Tesla BS-487B instrument in deuterochloroform with reference to TMS. The IR spectra were recorded on a UR-20 spectrophotometer for films.

  14. Antiarrhythmic, hypotensive and ?1-adrenolytic properties of new 2-methoxyphenylpiperazine derivatives of xanthone.

    PubMed

    Rapacz, Anna; Pytka, Karolina; Sapa, Jacek; Kubacka, Monika; Filipek, Barbara; Szkaradek, Natalia; Marona, Henryk

    2014-07-15

    The main goal of this study was to assess antiarrhythmic and hypotensive activity of new 2-methoxyphenylpiperazine derivatives of xanthone. In order to better understand mechanism of action of studied compounds, their abilities to antagonize the increase in blood pressure elicited by adrenaline, noradrenaline and methoxamine, as well as the antagonistic properties for ?1-adrenoceptors on isolated rat aorta were evaluated. Therapeutic antiarrhythmic activity was investigated in an adrenaline-induced model of arrhythmia. Hypotensive activity in normotensive rats was evaluated after oral administration. Influence on blood vasopressor response and ?1-adrenoceptors in rat thoracic aorta was evaluated to determine if the observed cardiovascular effects could be related to ?1-adrenolytic properties. Tested compounds produced antiarrhythmic and hypotensive activity. The most active compound was MH-99 - (R,S)-4-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one hydrochloride. All studied compounds showed ?1-adrenolytic properties in the in vivo and in vitro tests. The results indicate that the new valuable compounds with antiarrhythmic and hypotensive activity might be found in the group of xanthone derivatives. Further pharmacological utility of these compounds should be investigated. PMID:24751714

  15. Enrofloxacin hydro­chloride dihydrate

    PubMed Central

    Miranda-Calderón, Jorge E.; Gutiérrez, Lilia; Flores-Alamo, Marcos; García-Gutiérrez, Ponciano; Sumano, Héctor

    2014-01-01

    The asymmetric unit of the title compound, C19H23FN3O3 +·Cl?·2H2O [systematic name: 4-(3-carb­oxy-1-cyclo­propyl-6-fluoro-4-oxo-1,4-di­hydro­quin­o­lin-7-yl)-1-ethyl­piperazin-1-ium chloride dihydrate], consists of two independent monocations of the protonated enrofloxacin, two chloride anions and four water mol­ecules. In the cations, the piperazinium rings adopt chair conformations and the dihedral angles between the cyclo­propyl ring and the 10-membered quinoline ring system are 56.55?(2) and 51.11?(2)°. An intra­molecular O—H?O hydrogen bond is observed in each cation. In the crystal, the components are connected via O—H?Cl, N—H?Cl and O—H?O hydrogen bonds, and a ?–? inter­action between the benzene rings [centroid–centroid distance = 3.6726?(13)?Å], resulting in a three-dimensional array. PMID:24826167

  16. In Vivo and In Vitro Characterization of a First-in-Class Novel Azole Analog That Targets Pregnane X Receptor ActivationS?

    PubMed Central

    Venkatesh, Madhukumar; Wang, Hongwei; Cayer, Julie; Leroux, Melissa; Salvail, Dany; Das, Bhaskar; Wrobel, Jay E.

    2011-01-01

    The pregnane X receptor (PXR) is a master regulator of xenobiotic clearance and is implicated in deleterious drug interactions (e.g., acetaminophen hepatotoxicity) and cancer drug resistance. However, small-molecule targeting of this receptor has been difficult; to date, directed synthesis of a relatively specific PXR inhibitor has remained elusive. Here we report the development and characterization of a first-in-class novel azole analog [1-(4-(4-(((2R,4S)-2-(2,4-difluorophenyl)-2-methyl-1,3-dioxolan-4-yl)methoxy)phenyl)piperazin-1-yl)ethanone (FLB-12)] that antagonizes the activated state of PXR with limited effects on other related nuclear receptors (i.e., liver X receptor, farnesoid X receptor, estrogen receptor ?, peroxisome proliferator-activated receptor ?, and mouse constitutive androstane receptor). We investigated the toxicity and PXR antagonist effect of FLB-12 in vivo. Compared with ketoconazole, a prototypical PXR antagonist, FLB-12 is significantly less toxic to hepatocytes. FLB-12 significantly inhibits the PXR-activated loss of righting reflex to 2,2,2-tribromoethanol (Avertin) in vivo, abrogates PXR-mediated resistance to 7-ethyl-10-hydroxycamptothecin (SN-38) in colon cancer cells in vitro, and attenuates PXR-mediated acetaminophen hepatotoxicity in vivo. Thus, relatively selective targeting of PXR by antagonists is feasible and warrants further investigation. This class of agents is suitable for development as chemical probes of PXR function as well as potential PXR-directed therapeutics. PMID:21464197

  17. Recreational Use, Analysis and Toxicity of Tryptamines

    PubMed Central

    Tittarelli, Roberta; Mannocchi, Giulio; Pantano, Flaminia; Romolo, Francesco Saverio

    2015-01-01

    The definition New psychoactive substances (NPS) refers to emerging drugs whose chemical structures are similar to other psychoactive compounds but not identical, representing a “legal” alternative to internationally controlled drugs. There are many categories of NPS, such as synthetic cannabinoids, synthetic cathinones, phenylethylamines, piperazines, ketamine derivatives and tryptamines. Tryptamines are naturally occurring compounds, which can derive from the amino acid tryptophan by several biosynthetic pathways: their structure is a combination of a benzene ring and a pyrrole ring, with the addition of a 2-carbon side chain. Tryptamines include serotonin and melatonin as well as other compounds known for their hallucinogenic properties, such as psilocybin in ‘Magic mushrooms’ and dimethyltryptamine (DMT) in Ayahuasca brews. Aim: To review the scientific literature regarding tryptamines and their derivatives, providing a summary of all the available information about the structure of these compounds, their effects in relationship with the routes of administration, their pharmacology and toxicity, including articles reporting cases of death related to intake of these substances. Methods: A comprehensive review of the published scientific literature was performed, using also non peer-reviewed information sources, such as books, government publications and drug user web fora. Conclusions: Information from Internet and from published scientific literature, organized in the way we proposed in this review, provides an effective tool for specialists facing the emerging NPS threat to public health and public security, including the personnel working in Emergency Department. PMID:26074742

  18. LZ-207, a Newly Synthesized Flavonoid, Induces Apoptosis and Suppresses Inflammation-Related Colon Cancer by Inhibiting the NF-?B Signaling Pathway

    PubMed Central

    Sun, Jie; Li, Fanni; Zhao, Yue; Zhao, Li; Qiao, Chen; Li, Zhiyu; Guo, Qinglong; Lu, Na

    2015-01-01

    Flavonoids and flavonoid derivatives, which have significant biological and pharmacological activities, including antitumor and anti-inflammatory activities, have been widely used in human healthcare. To design a more effective flavonoid antitumor agent, we altered the flavonoid backbone with substitutions of piperazine and methoxy groups to synthesize a novel flavonoid derivative, LZ-207. The anticancer effect of LZ-207 against HCT116 colon cancer cells and the underlying mechanism of this effect were explored in this study. Specifically, LZ-207 exhibited inhibitory effects on growth and viability in several human colon cancer cell lines and induced apoptosis in HCT116 cells both in vitro and in vivo. LZ-207 treatment also suppressed the nuclear translocation of NF-?B and the phosphorylation of I?B and IKK?/? in a dose-dependent manner in both HCT116 cells and human acute monocytic leukemia THP-1 cells. Moreover, LZ-207 also reduced the secretion of the pro-inflammatory cytokine interleukin-6 (IL-6) in LPS-induced THP-1 cells, and this effect was confirmed at the transcriptional level. Furthermore, LZ-207 significantly inhibited HCT116 cell proliferation that was elicited by LPS-induced THP-1 cells in a co-culture system. These findings elucidated some potential molecular mechanisms for preventing inflammation-driven colon cancer using the newly synthesized flavonoid LZ-207 and suggested the possibility of further developing novel therapeutic agents derived from flavonoids. PMID:26023926

  19. Three organically templated magnesium sulfates: Chemical preparation, hydrogen-bonded structures and thermal behavior

    NASA Astrophysics Data System (ADS)

    Rekik, Walid; Naïli, Houcine; Mhiri, Tahar; Bataille, Thierry

    2012-10-01

    Three new organically templated magnesium sulfates using ethylenediamine, dabco and piperazine have been synthesized by the slow evaporation method and structurally characterized by single-crystal X-ray diffraction. The chemical purity of the products and the presence of the different entities building the compounds were tested by the EDAX measurements, chemical analysis of the elements and the IR spectroscopy. Compound (I), (C2H10N2)[Mg(SO4)2(H2O)4], crystallizes in the triclinic system, space group P -1, while both hybrid materials (C4H12N2)[Mg(H2O)6](SO4)2 (II) and (C6H14N2)[Mg(H2O)6](SO4)2 (III) adopt another structure type and they crystallize in the monoclinic system, space group C2/c. The three supramolecular compounds are built from anions and cations linked together through a 3-D hydrogen bond network. The thermal decomposition of precursors, studied by thermogravimetric analysis (TG) and temperature-dependent X-ray diffraction (TDXD), show successive intermediate hydrates and crystalline anhydrous compounds upon dehydration.

  20. CO2 CAPTURE BY ABSORPTION WITH POTASSIUM CARBONATE

    SciTech Connect

    Gary T. Rochelle; Eric Chen; Jennifer Lu; Babatunde Oyenekan; Ross Dugas

    2004-11-08

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. The stripper model with Aspen Custom Modeler and careful optimization of solvent rate suggests that 7 m MEA and 5 m K+/2.5 m PZ will be practically equivalent in energy requirement and optimum solution capacity. The multipressure stripper reduces energy consumption by 15% with a maximum pressure of 5 atm. The use of vanadium as a corrosion inhibitor will carry little risk of long-term environmental or health effects liability, but the disposal of solvent with vanadium will be subject to regulation, probably as a hazardous waste. Analysis of the pilot plant data from Campaign 1 has given values of the mass transfer coefficient consistent with the rate data from the wetted wall column. With a rich end pinch, 30% MEA should provide a capacity of 1.3-1.4 mole CO{sub 2}/kg solvent.

  1. Evidences for the involvement of sigma receptors in antidepressant like effect of quetiapine in mice.

    PubMed

    Kotagale, Nandkishor R; Mendhi, Sachin M; Aglawe, Manish M; Umekar, Milind J; Taksande, Brijesh G

    2013-02-28

    Although quetiapine is routinely used in the treatment of schizophrenia and bipolar disorders, the precise mechanism of its antidepressant activity is poorly understood. Since quetiapine binds with sigma receptor, the possibility exists that antidepressant action of quetiapine may be mediated through interaction with sigma receptors. In the present study, quetiapine [40-80 ?g/mouse, intracerebroventricular (i.c.v.) and 40 mg/kg, intraperitoneal (i.p.)], sigma1 receptor agonist, (+)-pentazocine (120 ?g/mouse, i.c.v.) and sigma2 receptor agonist, PB-28 [1-Cyclohexyl-4-[3-(1,2,3,4-tetrahydro-5-methoxy-1-naphthalenyl)propyl]piperazine] (20 ?g/mouse, i.c.v.) significantly decreased immobility time in forced swim test. In combination studies, the antiimmobility effect of quetiapine (20 ?g/mouse, i.c.v.) was significantly potentiated by pretreatment with (+)-pentazocine (30 and 60 ?g/mouse, i.c.v.) or PB-28 (5 and 10 ?g/mouse, i.c.v.). Conversely, prior administration of sigma1 receptor antagonist, BD-1063 [1-[2-(3,4-Dichlorophenyl)ethyl]-4-methylpiperazine] and sigma2 receptor antagonists, SM-21 [(±)-Tropanyl 2-(4-chlorophenoxy)butanoate] antagonized the antiimmobility effect induced by quetiapine and its synergistic combination with sigma receptor agonists. These results demonstrated the involvement of sigma receptors in the antidepressant like effect of quetiapine and suggest that sigma receptors can be explored as a potential therapeutic target for the treatment of depressive disorders. PMID:23399765

  2. Pharmacological evaluation of SN79, a sigma (?) receptor ligand, against methamphetamine-induced neurotoxicity in vivo.

    PubMed

    Kaushal, Nidhi; Seminerio, Michael J; Robson, Matthew J; McCurdy, Christopher R; Matsumoto, Rae R

    2013-08-01

    Methamphetamine is a highly addictive psychostimulant drug of abuse, causing hyperthermia and neurotoxicity at high doses. Currently, there is no clinically proven pharmacotherapy to treat these effects of methamphetamine, necessitating identification of potential novel therapeutic targets. Earlier studies showed that methamphetamine binds to sigma (?) receptors in the brain at physiologically relevant concentrations, where it "acts in part as an agonist." SN79 (6-acetyl-3-(4-(4-(4-florophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one) was synthesized as a putative ? receptor antagonist with nanomolar affinity and selectivity for ? receptors over 57 other binding sites. SN79 pretreatment afforded protection against methamphetamine-induced hyperthermia and striatal dopaminergic and serotonergic neurotoxicity in male, Swiss Webster mice (measured as depletions in striatal dopamine and serotonin levels, and reductions in striatal dopamine and serotonin transporter expression levels). In contrast, di-o-tolylguanidine (DTG), a well established ? receptor agonist, increased the lethal effects of methamphetamine, although it did not further exacerbate methamphetamine-induced hyperthermia. Together, the data implicate ? receptors in the direct modulation of some effects of methamphetamine such as lethality, while having a modulatory role which can mitigate other methamphetamine-induced effects such as hyperthermia and neurotoxicity. PMID:22921523

  3. Repurposing the Open Access Malaria Box To Discover Potent Inhibitors of Toxoplasma gondii and Entamoeba histolytica

    PubMed Central

    Fokou, Patrick V. T.; Tchokouaha, Lauve R. Y.; Spangenberg, Thomas; Mfopa, Alvine N.; Kouipou, Ruffin M. T.; Mbouna, Cedric J.; Donfack, Valerie F. Donkeng; Zollo, Paul H. A.

    2014-01-01

    Toxoplasmosis and amebiasis are important public health concerns worldwide. The drugs currently available to control these diseases have proven limitations. Therefore, innovative approaches should be adopted to identify and develop new leads from novel scaffolds exhibiting novel modes of action. In this paper, we describe results from the screening of compounds in the Medicines for Malaria Venture (MMV) open access Malaria Box in a search for new anti-Toxoplasma and anti-Entamoeba agents. Standard in vitro phenotypic screening procedures were adopted to assess their biological activities. Seven anti-Toxoplasma compounds with a 50% inhibitory concentration (IC50) of <5 ?M and selectivity indexes (SI) of >6 were identified. The most interesting compound was MMV007791, a piperazine acetamide, which has an IC50 of 0.19 ?M and a selectivity index of >157. Also, we identified two compounds, MMV666600 and MMV006861, with modest activities against Entamoeba histolytica, with IC50s of 10.66 ?M and 15.58 ?M, respectively. The anti-Toxoplasma compounds identified in this study belong to scaffold types different from those of currently used drugs, underscoring their novelty and potential as starting points for the development of new antitoxoplasmosis drugs with novel modes of action. PMID:25049259

  4. Multitarget-directed tricyclic pyridazinones as g?protein-coupled receptor ligands and cholinesterase inhibitors.

    PubMed

    Pau, Amedeo; Catto, Marco; Pinna, Giovanni; Frau, Simona; Murineddu, Gabriele; Asproni, Battistina; Curzu, Maria M; Pisani, Leonardo; Leonetti, Francesco; Loza, Maria Isabel; Brea, José; Pinna, Gérard A; Carotti, Angelo

    2015-06-01

    By following a multitarget ligand design approach, a library of 47 compounds was prepared, and they were tested as binders of selected G?protein-coupled receptors (GPCRs) and inhibitors of acetyl and/or butyryl cholinesterase. The newly designed ligands feature pyridazinone-based tricyclic scaffolds connected through alkyl chains of variable length to proper amine moieties (e.g., substituted piperazines or piperidines) for GPCR and cholinesterase (ChE) molecular recognition. The compounds were tested at three different GPCRs, namely serotoninergic 5-HT1A , adrenergic ?1A , and dopaminergic D2 receptors. Our main goal was the discovery of compounds that exhibit, in addition to ChE inhibition, antagonist activity at 5-HT1A because of its involvement in neuronal deficits typical of Alzheimer's and other neurodegenerative diseases. Ligands with nanomolar affinity for the tested GPCRs were discovered, but most of them behaved as dual antagonists of ?1A and 5-HT1A receptors. Nevertheless, several compounds displaying this GPCR affinity profile also showed moderate to good inhibition of AChE and BChE, thus deserving further investigations to exploit the therapeutic potential of such unusual biological profiles. PMID:25924828

  5. Fabrication and application of a new modified electrochemical sensor using nano-silica and a newly synthesized Schiff base for simultaneous determination of Cd2+, Cu2+ and Hg2+ ions in water and some foodstuff samples.

    PubMed

    Afkhami, Abbas; Soltani-Felehgari, Farzaneh; Madrakian, Tayyebeh; Ghaedi, Hamed; Rezaeivala, Majid

    2013-04-10

    A new chemically modified carbon paste electrode was constructed and used for rapid, simple, accurate, selective and highly sensitive simultaneous determination of cadmium, copper and mercury using square wave anodic stripping voltammetry (SWASV). The carbon paste electrode was modified by N,N'-bis(3-(2-thenylidenimino)propyl)piperazine coated silica nanoparticles. Compared with carbon paste electrode, the stripping peak currents had a significant increase at the modified electrode. Under the optimized conditions (deposition potential, -1.100 V vs. Ag/AgCl; deposition time, 60s; resting time, 10s; SW frequency, 25 Hz; pulse amplitude, 0.15 V; dc voltage step height, 4.4 mV), the detection limit was 0.3, 0.1 and 0.05 ng mL(-1) for the determination of Cd(2+), Cu(2+) and Hg(2+), respectively. The complexation reaction of the ligand with several metal cations in methanol was studied and the stability constants of the complexes were obtained. The effects of different cations and anions on the simultaneous determination of metal ions were studied and it was found that the electrode is highly selective for the simultaneous determination of Cd(2+), Cu(2+) and Hg(2+). Furthermore, the present method was applied to the determination of Cd(2+), Cu(2+) and Hg(2+) in water and some foodstuff samples. PMID:23522108

  6. Dopamine transport sites selectively labeled by a novel photoaffinity probe: 125I-DEEP

    SciTech Connect

    Grigoriadis, D.E.; Wilson, A.A.; Lew, R.; Sharkey, J.S.; Kuhar, M.J. (National Institute on Drug Abuse, Baltimore, MD (USA))

    1989-08-01

    The dopamine transporter was labeled using a photosensitive compound related to GBR-12909, {sup 125}I-1-(2-(diphenylmethoxy)ethyl)-4-(2- (4-azido-3-iodophenyl)ethyl)piperazine ({sup 125}I-DEEP). {sup 125}I-DEEP bound reversibly and with high affinity to the dopamine transport protein in the absence of light and could be covalently attached to the protein following exposure to UV light. In rat striatal homogenates, {sup 125}I-DEEP was found to incorporate covalently into a protein with apparent molecular weight of 58,000 Da. The properties of this binding protein were characteristic of the dopamine transporter since covalent attachment could be inhibited by dopamine-uptake blockers with the proper pharmacological rank order of potencies. Covalent binding was also inhibited in a stereospecific manner by (+) and (-) cocaine, as well as other cocaine analogs. The protein was not found in the cerebellum. The dopamine transporter appears to exist in a glycosylated form since photoaffinity-labeled transport sites could adsorb to wheat germ-agglutinin and could be specifically eluted from the column by beta-N-acetylglucosamine.

  7. Synthesis, structure and characterization of two new open-framework gallium phosphite-oxalates of varying dimensionality

    NASA Astrophysics Data System (ADS)

    Li, Caixia; Huang, Liangliang; Zhou, Mingdong; Xia, Jing; Ma, Hongwei; Zang, Shuliang; Wang, Li

    2013-12-01

    Using N, N-dimethyl-piperazine as structure directing agent, two new gallium phosphite-oxalates [Ga2(HPO3)2(H2PO3)2(C2O4)](C6N2H16) (I) and [Ga2(HPO3)2(H2PO3)(C2O4)](C6N2H16)0.5 (II) have been synthesized under solvothermal and hydrothermal conditions, respectively and further characterized by powder X-ray diffraction, IR spectroscopy, TGA, ICP-AES and elemental analyses. Single crystal X-ray diffraction reveals that the striking feature of I and II is that they possess the same second building unit (SBU) Ga2P2 constructed from two GaO6 octahedra and two [HPO32-] pseudo-pyramids sharing oxygen atoms. However, due to the different connecting fashions of SBUs, [C2O42-] groups and [H2PO3-] pseudo-pyramids, the final frameworks of them are distinctly different. Compound I shows 2D layered structures with 8-membered ring (8-MR) windows in the ab plane while compound II presents a 3D open-framework with 8-MR channels along the b axis.

  8. Synthesis and evaluation of a new series of 3,5-bis((5-bromo-6-methyl-2-t-aminopyrimidin-4-yl)thio)-4H-1,2,4-triazol-4-amines and their cyclized products 'pyrimidinylthio pyrimidotriazolothiadiazines' as 15- lipo-oxygenase inhibitors.

    PubMed

    Asghari, Tayebe; Bakavoli, Mehdi; Rahimizadeh, Mohammad; Eshghi, Hossein; Saberi, Sattar; Karimian, Azam; Hadizadeh, Farzin; Ghandadi, Moreteza

    2015-02-01

    A series of new 3,5-bis((5-bromo-6-methyl-2-t-aminopyrimidin-4-yl)thio)-4H-1,2,4-triazol-4-amines and their cyclized products 'pyrimidinylthio pyrimidotriazolothiadiazines' were designed, synthesized, and evaluated as potential inhibitors of 15-lipo-oxygenase (15-LO). Their syntheses started by initial condensation of 2:1 equivalents of pyrimidine with triazole and subsequent nucleophilic displacement of the chlorine atoms with secondary amines and finally cyclocondensation in the presence of NaNH2. The compounds 4d and 4f showed the best IC50 of 15-LO inhibition (IC50 = 9 and 12 ?m, respectively). Compounds 4a-g were docked into 15-LO. We suggest that the hydrogen bonds in quaternary nitrogen of piperazine ring of compounds 4d and 4f appear to play major role in lipo-oxygenase inhibition by this set of synthesized analogs and hydrophobic nature of this protein's binding site should be considered in ongoing investigations. PMID:24925519

  9. Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signaling.

    PubMed

    Liechti, Matthias

    2015-01-01

    Novel psychoactive substances are newly used designer drugs ("internet drugs", "research chemicals", "legal highs") potentially posing similar health risks to classic illicit substances. Chemically, many novel psychoactive substances can be classified as phenethylamines, amphetamines, synthetic cathinones, piperazines, pipradrols/piperidines, aminoindanes benzofurans, and tryptamines. Pharmacologically, these substances interact with various monoaminergic targets. Typically, stimulants inhibit the transport of dopamine and noradrenaline (pipradrols, pyrovalerone cathinones) or induce the release of these monoamines (amphetamines and methamphetamine-like cathinones), entactogens predominantly enhance serotonin release (phenylpiperazines, aminoindanes, para-substituted amphetamines, and MDMA-like cathinones) similar to MDMA (ecstasy), and hallucinogens (tryptamines, hallucinogenic phenethylamines) are direct agonists at serotonergic 5-HT2A receptors. Synthetic cannabinoids are another group of novel substances which all act as agonists at the cannabinoid CB1 receptor similar to THC but are chemically diverse. In particular, the relative serotonergic vs dopaminergic activity (determined by the dopamine/serotonin transporter inhibition ratio in vitro) can be helpful to predict the desired psychotropic but also the toxic effects of novel substances as well as their potential for addiction. Although the use of novel psychoactive substances mostly produces minor or moderate poisonings, serious complications occur. Serotonergic drugs (entactogens and hallucinogens) are associated with acute serotonin syndrome, hyperthermia, seizures, and hyponatremia. Dopaminergic drugs are highly addictive and acute toxicity includes prolonged stimulation, insomnia, agitation, and psychosis. Agitation, anxiety, paranoia, hypertension, and rarely myocardial infarction and renal failure are seen with synthetic cannabinoids. Treatment is supportive. PMID:25588018

  10. Broad-Spectrum Anti-Cancer Activity of O2-Arylated Diazeniumdiolates

    PubMed Central

    Keefer, Larry K.

    2011-01-01

    O2-(2,4-Dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) and O2-{2,4-dinitro-5-[4-(N-methylamino)be nzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate (PABA/NO) are O2-arylated diazeniumdiolates that have shown promising in vivo activity in a variety of rodent cancer models, including prostate cancer, leukemia, liver cancer, multiple myeloma, and ovarian cancer. This compound class was designed to be activated for anti-cancer effects by glutathione-S-transferase (GST)-induced release of cytotoxic nitric oxide (NO), but mechanistic studies have implicated a variety of pathways, some GST/NO-related, some not. Current work is focused on improving formulations and other drug development activities, as well as exploring possible new applications of these agents and their analogs. The selectivity of these drugs for attacking tumors while exhibiting little toxicity toward normal tissues suggests considerable promise for the treatment of various tumor types. PMID:21949595

  11. Nitric oxide (NO) releasing poly ADP-ribose polymerase 1 (PARP-1) inhibitors targeted to glutathione S-transferase P1-overexpressing cancer cells.

    PubMed

    Maciag, Anna E; Holland, Ryan J; Kim, Youseung; Kumari, Vandana; Luthers, Christina E; Sehareen, Waheed S; Biswas, Debanjan; Morris, Nicole L; Ji, Xinhua; Anderson, Lucy M; Saavedra, Joseph E; Keefer, Larry K

    2014-03-27

    We report the antitumor effects of nitric oxide (NO) releasing derivatives of the PARP-1 inhibitor olaparib (1). Compound 5b was prepared by coupling the carboxyl group of 3b and the free amino group of arylated diazeniumdiolated piperazine 4. Analogue 5a has the same structure except that the F is replaced by H. Compound 13 is the same as 5b except that a Me2N-N(O)?NO- group was added para and ortho to the nitro groups of the dinitrophenyl ring. The resulting prodrugs are activated by glutathione in a reaction accelerated by glutathione S-transferase P1 (GSTP1), an enzyme frequently overexpressed in cancers. This metabolism generates NO plus a PARP-1 inhibitor simultaneously, consuming reducing equivalents, leading to DNA damage concomitant with inhibition of DNA repair, and in the case of 13 inducing cross-linking glutathionylation of proteins. Compounds 5b and 13 reduced the growth rates of A549 human lung adenocarcinoma xenografts with no evidence of systemic toxicity. PMID:24521039

  12. Identification and Characterization of a Novel Integrin-Linked Kinase Inhibitor

    PubMed Central

    Lee, Su-Lin; Hsu, En-Chi; Chou, Chih-Chien; Chuang, Hsiao-Ching; Bai, Li-Yuan; Kulp, Samuel K.; Chen, Ching-Shih

    2011-01-01

    Integrin-linked kinase (ILK) represents a relevant target for cancer therapy in light of its role in promoting oncogenesis and tumor progression. Through the screening of an in-house focused compound library, we identified N-Methyl-3-(1-(4-(piperazin-1-yl)phenyl)-5-(4?-(trifluoromethyl)-[1,1?-biphenyl]-4-yl)-1H-pyrazol-3-yl)propanamide (22) as a novel ILK inhibitor (IC50, 0.6 ?M), which exhibited high in vitro potency against a panel of prostate and breast cancer cell lines (IC50, 1 – 2.5 ?M), while normal epithelial cells were unaffected. Compound 22 facilitated the dephosphorylation of Akt at Ser-473 and other ILK targets, including glycogen synthase kinase-3? and myosin light chain. Moreover, 22 suppressed the expression of the transcription/translation factor YB-1 and its targets HER2 and EGFR in PC-3 cells, which could be rescued by the stable expression of constitutively active ILK. Evidence indicates that 22 induced autophagy and apoptosis, both of which were integral to its antiproliferative activity. Together, this broad spectrum of mechanisms underlies the therapeutic potential of 22 in cancer treatment, which is manifested by its in vivo efficacy as a single oral agent in suppressing PC-3 xenograft tumor growth. PMID:21823616

  13. Complexation of N4-Tetradentate Ligands with Nd(III) and Am(III)

    SciTech Connect

    Ogden, Mark D.; Sinkov, Sergey I.; Meier, G. Patrick; Lumetta, Gregg J.; Nash, Kenneth L.

    2012-12-06

    To improve understanding of aza-complexants in trivalent actinide–lanthanide separations, a series of tetradentate N-donor ligands have been synthesized and their complexation of americium(III) and neodymium(III) investigated by UV–visible spectrophotometry in methanolic solutions. The six pyridine/alkyl amine/imine ligands are N,N0-bis(2-methylpyridyl)-1,2-diaminoethane, N,N0-bis(2-methylpyridyl)-1,3-diaminopropane, trans-N,N-bis(2-pyridylmethyl)-1,2-diaminocyclohexane (BPMDAC), N,N’-bis(2-pyridylmethyl)piperazine, N,N’-bis-[pyridin-2-ylmethylene]ethane-1,2-diamine, and trans-N,Nbis-([pyridin-2-ylmethylene]-cyclohexane-1,2-diamine. Each ligand has two pyridine groups and two aliphatic amine/imine N-donor atoms arranged with different degrees of preorganization and structural backbone rigidity. Conditional stability constants for the complexes of Am(III) and Nd(III) by these ligands establish the selectivity patterns. The overall selectivity of Am(III) over Nd(III) is similar to that reported for the terdentate bis(dialkyltriazinyl)pyridine molecules. The cyclohexane amine derivative (BPMDAC) is the strongest complexant and shows the highest selectivity for Am(III) over Nd(III) while the imines appear to prefer a bridging arrangement between two cations. These results suggest that this series of ligands could be employed to develop an enhanced actinide(III)– lanthanide(III) separation system.

  14. Bioequivalence study of two tablet formulations of sildenafil.

    PubMed

    Spínola, Ana Cristina Franco; Almeida, Susana; Filipe, Augusto; Tanguay, Mario; Yritia, Mercedes

    2008-01-01

    This study was conducted in order to assess the bioequivalence of two tablet formulations containing 100 mg sildenafil (1-[4-ethoxy-3-(6,7-dihydro-1-,ethyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenylsulphonyl] -4-methyl piperazine, CAS 139755-83-2). Twenty-eight healthy subjects were enrolled in a single-centre, randomised, single-dose, open-label, 2-way crossover study, with a minimum washout period of 7 days. Plasma samples were collected up to 18.0 h postdosing. Sildenafil levels were determined by reverse liquid chromatography coupled with tandem mass spectrometry detection (LC-MS/MS). Pharmacokinetic parameters used for bioequivalence assessment [area under the concentration-time curve from time zero to time of last non-zero concentration (AUC(last)) and maximum observed concentration (C(max)) were main evaluation criteria; however, the area under the concentration-time curve from time zero to infinity (AUC(inf)) was also analysed] were determined from the sildenafil concentration data using non-compartmental analysis. The 90% confidence intervals (obtained by analysis of variance, ANOVA) were 86.70-108.19 for C(max), 86.67-99.26 for AUC(last) and 87.19-99.82 for AUC(inf) within the predefined ranges. Bioequivalence between the two formulations was concluded both in terms of rate and extent of absorption. PMID:18488808

  15. Synthesis, structures, luminescent and magnetic properties of four coordination polymers with the flexible 1,3-phenylenediacetate ligands

    NASA Astrophysics Data System (ADS)

    Gu, Jin-Zhong; Lv, Dong-Yu; Gao, Zhu-Qing; Liu, Jian-Zhao; Dou, Wei; Tang, Yu

    2011-03-01

    Four coordination polymers, [Zn(pda)(bpy)(H 2O)] n· nH 2O ( 1), [Cd(pda)(prz)(H 2O)] n ( 2), [Co 3( ?3-OH) 2(pda) 2(pyz)] n·2 nH 2O ( 3) and [Pr 2(pda) 3(H 2O) 2] n ( 4) (H 2pda=1,3-phenylendiacetic acid, bpy=4,4'-bipyridine, prz=piperazine and pyz=pyrazine) have been hydrothermally synthesized and characterized. Complex 1 is a 1D wheel-like chain structure, which is further extended into a 3D metal-organic supramolecular framework by H-bonds and ?- ? stacking interactions. Complex 2 is a 1D ladder-like chain structure, which is also further extended into a 3D metal-organic supramolecular framework by H-bonds. Complex 3 possess a 2D sheet structure with infrequent two pairs of double-helix chains. Complex 4 features a 3D structure. Both 1 and 2 display strong blue fluorescent emission at room temperature. Magnetic susceptibility measurements of complexes 3 and 4 exhibit antiferromagnetic interactions between the nearest metal ions, with C=9.99 and 3.43 cm 3 mol -1 K, and ?=-23.9 and -46.3 K, respectively.

  16. Preparation and performance of novel thermally stable polyamide/PPENK composite nanofiltration membranes

    NASA Astrophysics Data System (ADS)

    Hu, Lijie; Zhang, Shouhai; Han, Runlin; Jian, Xigao

    2012-09-01

    Novel thermally stable composite nanofiltration (NF) membranes were prepared from piperazine (PIP) and trimesoyl chloride (TMC) on poly (phthalazione ether nitrile ketone) (PPENK) ultrafiltration (UF) membranes by interfacial polymerization. The effects of monomers concentration, reaction time and organic solvents on the performance of composite membranes were investigated. The effects of operating pressure and the salt solution concentration on the performance of composite membranes were also discussed. The different salts rejection of PPENK composite membranes decreased in the order of Na2SO4 > MgSO4 > Al2(SO4)3 > NaCl > MgCl2, which indicated a negative charge at the membrane surface. The flux and Na2SO4 rejection of PPENK composite membranes reached 57.9 L/m2 h and 98.4% under the optimized conditions and operating pressure of 1.0 MPa. Furthermore, the morphology and chemical structure of membranes were examined by scanning electronic microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR), respectively. Moreover, the thermal stability of PPENK NF membranes was also investigated. When temperature of the feed solution raised from 20 °C to 80 °C, the permeation flux increased about four times without significant change of rejection. The flux increased first then reached a plateau and the rejection kept constant when PPENK NF membranes in boiling de-ionized water were boiled to 3 h.

  17. Triprotic site-specific acid-base equilibria and related properties of fluoroquinolone antibacterials.

    PubMed

    Rusu, Aura; Tóth, Gerg?; Sz?cs, Levente; Kökösi, József; Kraszni, Márta; Gyéresi, Árpád; Noszál, Béla

    2012-07-01

    The complete macro- and microequilibrium analyses of six fluoroquinolone drugs - ciprofloxacin, enrofloxacin, norfloxacin, pefloxacin, ofloxacin and moxifloxacin - are presented. Previous controversial literature data are straightened up, the protonation centers are unambiguously identified, and the protonation macro- and microconstant values are reported. The macroconstants were determined by (1)H NMR-pH titrations while the microconstants were determined by a multi-modal spectroscopic-deductive methodology, in which methyl ester derivatives were synthesized and their NMR-pH titration data contributed to the evaluation of all the microconstants. The full (1)H, (13)C and (15)N NMR assignments, NMR-pH profiles, macro- and microprotonation schemes and species-specific diagrams are included. Our studies show that the fluoroquinolones have three protonation centers: the carboxylate group, the N-1' and N-4' piperazine nitrogens and concentration of the uncharged microspecies is way below the values published earlier. The results could be well interpreted in terms of structural properties. The protonation macro- and microconstant values allow the pre-planned method development in techniques such as capillary zone electrophoresis and also, the interpretation of fluoroquinolone mechanism of biological action, including the pharmacokinetic properties, and antibacterial activities that are all heavily influenced by the states of protonation. PMID:22464555

  18. High-pressure high-temperature behavior of polymer derived amorphous B-C-N

    NASA Astrophysics Data System (ADS)

    Bhat, Shrikant; Lauterbach, Stefan; Dzivenko, Dmytro; Lathe, Christian; Bayarjargal, Lkhamsuren; Schwarz, Marcus; Kleebe, Hans-Joachim; Kroke, Edwin; Winkler, Björn; Riedel, Ralf

    2014-05-01

    Abstract: Dense diamond-like BCN compounds are of interest due to their extreme hardness and predicted excellent thermal and chemical stability, which are superior to those of diamond and c-BN. Here, we report on the high-pressure high-temperature (HP-HT) behavior of amorphous BC2N and BC4N -as potential precursors for HP-HT synthesis of diamond-like BCN. Prepared via hydroboration reaction of piperazine borane and pyridine borane, respectively, amorphous BC2N and BC4N are characterized by well-mixed B-N, C-C and C-N bonds, confirmed by XPS analysis. These BCN compositions were subjected to pressures between 5-12 GPa and temperatures up to 1700 °C using multi-anvil apparatus and toroid-type press. In- and ex-situ X-ray diffraction reveals the decomposition of BC4N to graphite and h-BN between 5 and 12 GPa above 500 °C, in contrast to BC2N which remains amorphous up to 1600 °C.

  19. Detection of new psychoactive substance use among emergency room patients: results from the Swedish STRIDA project.

    PubMed

    Helander, Anders; Bäckberg, Matilda; Hultén, Peter; Al-Saffar, Yasir; Beck, Olof

    2014-10-01

    The "STRIDA" project monitors the occurrence and trends of new psychoactive substances (NPS; "Internet drugs/designer drugs/legal highs") in Sweden, and collects information about their clinical symptoms, toxicity and associated health hazards. The initial results of the project documented a widespread use of many different NPS by mainly adolescents and young (age range 13-63 years, median 20), male (79%) adults, among cases of drug intoxications presenting at emergency departments and intensive care units across the country. The new substances were identified in samples of urine and blood by a multi-component LC-MS/MS method, and the severity of clinical symptoms were graded by the Poisoning Severity Score (PSS). Of the initial 189 samples submitted for laboratory investigation, 156 (83%) tested positive for at least one drug. Besides classical substances such as ethanol, cannabis and amphetamines, many NPS were detected comprising synthetic cannabinoid receptor agonists ("Spice"), piperazines, substituted phenethylamines, synthetic cathinones, hallucinogenic tryptamines, piperidines, opioid related substances, ketamine and related substances, and GABA analogues (in total more than 50 substances). About half of the cases were demonstrated to be multiple drug intoxications, sometimes making it hard to associate the clinical presentations with one specific substance. In conclusion, the STRIDA project has documented use of a broad variety of NPS among mainly young people all over Sweden. PMID:24726531

  20. Increases in use of novel synthetic stimulant are not directly linked to decreased use of 3,4-methylenedioxy-N-methylamphetamine (MDMA).

    PubMed

    Chen, Chang; Kostakis, Chris; Irvine, Rodney J; White, Jason M

    2013-09-10

    A decline in 3,4-methylenedioxy-N-methylamphetamine (MDMA) use in Adelaide, Australia from 2009 to 2010 was confirmed by us previously. Reports suggested that the shortage in MDMA supply was associated with an increased prevalence of other synthetic stimulants, but quantitative measurements were unavailable. To obtain objective data on the community use of synthetic stimulants, we collected wastewater samples from multiple treatment plants in Adelaide, Australia from 2009 to 2011 and analysed them using solid-phase extraction/liquid chromatography/tandem mass spectrometry (SPE-LC-MS/MS), targeting MDMA and some of the most reported synthetic cathinones and piperazines. Data were temporally compared. MDMA and six other synthetic stimulants were detected and quantified in wastewater samples. While MDMA level decreased markedly from 2009 to 2010 and remained low in 2011, localized increased use of mephedrone, methylone, methylenedioxypyrovalerone (MDPV), benzylpiperazine (BZP), 3-trifluoromethylphenylpiperazine (TFMPP), but not methcathinone, was observed in 2010 and 2011. This suggested that the decline in MDMA use was associated with an increase in the use of a number of other synthetic stimulants. However, the lag time from the decrease in MDMA to the increase in use of a number of these stimulants, together with the highly regionalized use of all synthetic stimulants except methcathinone indicates that there was no direct population wide substitution in response to the reduction in MDMA. PMID:23890650