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Sample records for 1 3 4

  1. Preparation of 1,1'-dinitro-3,3'-azo-1,2,4-triazole. [1,1'-dinitro-3,3'-azo-1,2,4-triazole

    DOEpatents

    Lee, K.Y.

    1985-03-05

    A new high density composition of matter, 1,1'-dinitro-3,3'-azo-1,2,4-triazole, has been synthesized using inexpensive, commonly available compounds. This compound has been found to be an explosive, and its use as a propellant is anticipated. 1 fig., 1 tab.

  2. Synthesis of polyfunctional organochlorine compounds based on 1,1,1,2,3,3,4,4-octachlorobutane

    SciTech Connect

    Kaberdin, R.V.; Potkin, V.I.; Dubova, E.Yu.; Ol'dekop, Yu.A.

    1989-01-10

    2,3,3,4,4-Pentachlorobutyric acid was obtained with a preparative yield by the reaction of 1,1,1,2,3,3,4,4-octachlorobutane with oleum. The dehydroclorination of octachlorobutane with an equimolar amount of an aqueous solution of sodium hydroxide, catalyzed by triethylbenzylammonium chloride, takes place by the elimination of one molecule of hydrogen chloride from positions 1,2 and 2,3 with the formation of isomeric heptachlorobutenes. Hydrolysis of the latter with fuming nitric acid gave the difficulty obtainable 1,1,2,4,4-pentachloro-1-buten-3-one and Z-/alpha/,/beta/,/gamma/,/gamma/-tetrachlorocrotonic acid.

  3. Synthesis of 1,1'-dinitro-3,3'-azo-1,2,4-triazole

    SciTech Connect

    Lee, K.Y.

    1985-04-01

    A novel compound has been prepared and is a candidate for high-energy propellant applications. The 1,1'-dinitro-3,3'-azo-1,2,4-triazole (N-DNAT) has a density of 1.77 g/cm/sup 3/ and can be prepared from inexpensive starting materials.

  4. 40 CFR 721.10435 - Phenol, 2-(1-methyl-1-phenylethyl)-4-(1,1,3,3-tetramethylbutyl)-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phenol, 2-(1-methyl-1-phenylethyl)-4... Significant New Uses for Specific Chemical Substances § 721.10435 Phenol, 2-(1-methyl-1-phenylethyl)-4-(1,1,3... chemical substance identified as phenol, 2-(1-methyl-1-phenylethyl)-4-(1,1,3,3-tetramethylbutyl)- (PMN...

  5. 40 CFR 721.10435 - Phenol, 2-(1-methyl-1-phenylethyl)-4-(1,1,3,3-tetramethylbutyl)-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phenol, 2-(1-methyl-1-phenylethyl)-4... Significant New Uses for Specific Chemical Substances § 721.10435 Phenol, 2-(1-methyl-1-phenylethyl)-4-(1,1,3... chemical substance identified as phenol, 2-(1-methyl-1-phenylethyl)-4-(1,1,3,3-tetramethylbutyl)- (PMN...

  6. SAS 3 observations of GX 1 + 4

    NASA Technical Reports Server (NTRS)

    Doty, J. P.; Lewin, W. H. G.; Hoffman, J. A.

    1981-01-01

    GX 1 + 4 is one of the brightest celestial sources of high-energy X-rays. It is a pulsar with a period of approximately 2 min (perhaps a multiple of 2 min), decreasing at a variable rate which, since 1971, has averaged approximately 2% per year, but which can be larger than 5% per year. This is the largest rate of decrease observed for any pulsar. The rate of decrease appears to be correlated with the luminosity, in support of the idea that the period decrease is produced by accretion torques acting upon a neutron star. No evidence is seen for a Doppler shift due to motion of the pulsar in a binary orbit; this is consistent with the results of optical observations which suggest that any orbital period is fairly long (months to years). The spectrum of GX 1 + 4 is measured as a function of pulse phase, as well as the phase-averaged total spectrum, and the average spectrum of the pulses alone. The shape of the average pulsed spectrum suggests that the pulsations may be produced by 'hot spots' which are a few hundred meters in extent, with temperatures of approximately 10 to the 8th K (kT being approximately equal to 8 keV).

  7. Preparation of 1,1'-dinitro-3,3'-azo-1,2,4-triazole

    DOEpatents

    Lee, Kien-Yin

    1986-01-01

    A new high density composition of matter, 1,1'-dinitro-3,3'-azo-1,2,4-triazole, has been synthesized using inexpensive, commonly available compounds. This compound has been found to be an explosive, and its use as a propellant is anticipated.

  8. 40 CFR 721.10584 - Cyclopentene, 1,3,3,4,4,5,5-heptafluoro-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10584 Cyclopentene, 1,3,3,4,4,5,5-heptafluoro-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  9. 40 CFR 721.10584 - Cyclopentene, 1,3,3,4,4,5,5-heptafluoro-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10584 Cyclopentene, 1,3,3,4,4,5,5-heptafluoro-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  10. 40 CFR 721.10433 - Cyclopentene, 1,2,3,3,4,4,5,5-octafluoro-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....80(f) and (j) (dry etching agent and chemical vapor deposition agent for the production of...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10433 Cyclopentene, 1,2,3,3,4,4,5,5-octafluoro-. (a) Chemical...

  11. 40 CFR 721.10433 - Cyclopentene, 1,2,3,3,4,4,5,5-octafluoro-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....80(f) and (j) (dry etching agent and chemical vapor deposition agent for the production of...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10433 Cyclopentene, 1,2,3,3,4,4,5,5-octafluoro-. (a) Chemical...

  12. 4 CFR 3.1 - Appointment, promotion, and assignment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Appointment, promotion, and assignment. 3.1 Section 3.1 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM EMPLOYMENT § 3.1 Appointment, promotion, and assignment. Employees of GAO shall be appointed, promoted and assigned solely on the basis of merit...

  13. 1,2,3,3',4',6'-Hexaacetyl-4,6-O-benzyl-idenesucrose.

    PubMed

    Brito-Arias, Marco A; Soto-Ortega, Miguel; García-Báez, Efrén V

    2011-01-01

    In the title compound, C(31)H(38)O(17), the 1,3-dioxane and pyran-oside rings both show (4)C(1) chair conformations while for the d-fructofuran-oside moiety an envelop 3E conformation is observed. The phenyl ring is oriented almost perpendicular to the 1,3-dioxane ring [dihedral angle = 79.3 (2)°], and the acetate groups are equatorial for the pyran-oside ring and axial for the furan-oside ring. The analysis of potential hydrogen bonds shows both intra- and inter-molecular C-H⋯O contacts to be present. PMID:21523142

  14. Synthesis and enantioselectivity of optically active 1- and 3-substituted 4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols and related compounds as norepinephrine potentiators.

    PubMed

    Kihara, M; Ikeuchi, M; Adachi, S; Nagao, Y; Moritoki, H; Yamaguchi, M; Taira, Z

    1995-09-01

    Optically active 1,2-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols (1R,4R-3a and 1S,4S-3b, 1S,4R-4a, and 1R,4S-4b) and 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolines (4S-5a and 4R-5b) were prepared in order to examine the effects of the 1-, 3-, and 4-substituents of 2-methyl-4-phenyl- 1,2,3,4-tetrahydroisoquinolin-4-ol (PI-OH) (1) on the enantioselectivity for norepinephrine (NE) potentiating activity. The conformations and absolute configurations of 3-5 were determined from their 1H-NMR and circular dichroism (CD) spectra and by single-crystal X-ray diffractometric analysis. The NE potentiating activity of the optically active 3-5 and previously prepared 3-methyl derivatives (3R,4R-6a and 3S,4S-6b) of PI-OH were tested. The results show that compounds 3, 4, and 6 had high enantioselectivity for NE potentiation: the 4R series of the enantiomers exhibited activity but not the 4S-enantiomers. The activity of the 4-desoxy compound 5 also resided exclusively in the 4S-enantiomer. These findings suggest the presence of a specific receptor for NE uptake, and the enantiomers 3a, 4a, 5a, and 6a may be antagonistic at this NE uptake receptor. PMID:7586079

  15. Reaction of 1,2,4-triazole-3-thiones with 1-chloro-2,3-epoxypropane

    SciTech Connect

    Trzhtsinskaya, B.V.; Kositsyna, E.I.; Pertsikov, B.Z.; Rudakova, E.V.; Voronov, V.K.; Skvortsova, G.G.

    1987-08-01

    Addition of 1-chloro-2,3-epoxypropane to 1,2,4-triazole-3-thiones depending on the ratio of the reactants leads to the formation of 3-(1-chloro-2-hydroxypropyl)-3-(1-chloro-2-hydroxypropylthio)-1,2,4-triazoles. 3-Hydroxy-1,2,4-triazolo(2,3-b) tetrahydro-1,3-triazines have been synthesized by intramolecular cyclization of the monoadducts. IR spectra were recorded on a Specord 75-IR instrument as a thin layer, in KBr pellets, an in chloroform solution; PMR spectra were recorded on a Tesla BS-497 instrument (100 MHz) at 20/sup 0/C in CD/sub 3/OD with TMS as internal standard.

  16. ANCHOR SETTING PLAN FOR PIERS 1, 2, 3, 4, 5 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    ANCHOR SETTING PLAN FOR PIERS 1, 2, 3, 4, 5 AND 6, APALACHICOLA RIVER BRIDGE, SHEET 5505 TO 8-M1 - Apalachicola River Bridge, State Route 20 spanning the Apalachicola River, Blountstown, Calhoun County, FL

  17. Synthesis of 1,3,4-thiadiazole, 1,3,4-thiadiazine, 1,3,6-thiadiazepane and quinoxaline derivatives from symmetrical dithiobiureas and thioureidoethylthiourea derivatives.

    PubMed

    Hassan, Alaa A; Mourad, Aboul-Fetouh; El-Shaieb, Kamal M; Abou-Zied, Ashraf H

    2005-01-01

    Reactions of N,N;-disubstituted hydrazinecarbothioamides 8a-c and substituted thioureidoethylthioureas 9a-c with 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil, 10a) and 2,3,5,6-tetrabromo-1,4-benzoquinone (bromanil, 10b) to form N,N;-disubstituted [1,3,4]thiadiazole-2,5-diamines 11a-c, 6,7-dichloro-3-substituted amino-1H-benzo[1,3,4]- thiadiazine-5,8-diones 12a-c, 2,3,7,8-tetrahalothianthrene-1,4,6,9-tetraones 13a,b, 5,6,8- trihalo-7-oxo-3,7-dihydro-2H-quinoxaline-1-carbothioic acid substituted amides 14a-c, 15a-c and 7-substituted imino-[1,3,6]thiadiazepane-3-thiones 16a-c are reported. Rationales for the observed conversions are presented. PMID:18007352

  18. Propellant Containing 3, 6bis(1h-1,2,3,4-Tetrazol-5-Ylamino)-1,2,4,5- Tetrazine Or Salt Thereof

    DOEpatents

    Hiskey, Michael A.; Chavez, David E.; Naud, Darren

    2003-12-02

    The compound 3,6-bis(1H-1,2,3,4-tetrazol-5-ylamino)-1,2,4,5-tetrazine and its salts are provided together with a propellant composition including an oxidizer, a binder and 3,6-bis(1H-1,2,3,4-tetrazol-5-ylamino)-1,2,4,5-tetrazine or its salts.

  19. 10 CFR 960.3-1-4-3 - Site recommendation for characterization.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Site recommendation for characterization. 960.3-1-4-3 Section 960.3-1-4-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-3 Site...

  20. 10 CFR 960.3-1-4-3 - Site recommendation for characterization.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Site recommendation for characterization. 960.3-1-4-3 Section 960.3-1-4-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-3 Site...

  1. 10 CFR 960.3-1-4-3 - Site recommendation for characterization.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Site recommendation for characterization. 960.3-1-4-3 Section 960.3-1-4-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-3 Site...

  2. 10 CFR 960.3-1-4-3 - Site recommendation for characterization.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Site recommendation for characterization. 960.3-1-4-3 Section 960.3-1-4-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-3 Site...

  3. 10 CFR 960.3-1-4-3 - Site recommendation for characterization.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Site recommendation for characterization. 960.3-1-4-3 Section 960.3-1-4-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-3 Site...

  4. Synthesis, crystal structure, and biological activity of 4-methyl-1,2,3-thiadiazole-containing 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles.

    PubMed

    Fan, Zhijin; Yang, Zhikun; Zhang, Haike; Mi, Na; Wang, Huan; Cai, Fei; Zuo, Xiang; Zheng, Qingxiang; Song, Haibin

    2010-03-10

    Heterocyclic compounds play an important role as the main sources of lead molecules of agrochemicals. Synthesis and biological activity of thiadiazole-containing 1,2,4-triazolo[3,4-b][1,3,4]-thiadiazoles were seldom reported. To find novel lead compounds with various biological activities, a series of 6-substituted-3-(4-methyl-1,2,3-thiadiazolyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadizoles were rationally designed and synthesized according to the principle of combinations of bioactive substructures by the condensation of 3-(4-methyl-1,2,3-thiadiazolyl)-4-amino-1,2,4-triazole-5-thione with various carboxylic acids and phosphorus oxychloride. All newly synthesized compounds were identified by proton nuclear magnetic resonance ((1)H NMR), infrared spectroscopy (IR), electroionization mass spectrometry (EI/MS), and elementary analysis. The crystal structure of 3-(4-methyl-1,2,3-thiadiazolyl)-6-(4-methylphenyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadizole was determined by X-ray diffraction crystallography. In this crystal, two intermolecular hydrogen bonds (N2...H-C12 and N3...H-C13), a weak intermolecular interaction (S...S), and the weak ppi-ppi intermolecular interaction were observed. Fungicide screening indicated that all of the target compounds showed certain extent of growth inhibition against fungi tested. 3-(4-Methyl-1,2,3-thiadiazolyl)-6-n-propyl[1,2,4]triazolo[3,4-b][1,3,4]thiadizole and 3-(4-methyl-1,2,3-thiadiazolyl)-6-trichloromethyl[1,2,4]triazolo[3,4-b][1,3,4]thiadizole were found to have potential wide spectrum of fungicide activity. The median effective concentrations (EC(50)) detected for 3-(4-methyl-1,2,3-thiadiazolyl)-6-trichloromethyl[1,2,4]triazolo[3,4-b][1,3,4]thiadizole to six fungi were from 7.28 micromol/L against Pellicularia sasakii (Shirai) to 42.49 micromol/L against Alternaria solani . The results indicated that thiadiazole-containing 1,2,4-triazolo[3,4-b][1,3,4]-thiadiazoles were potential fungicide lead compounds. PMID:20014761

  5. VIEW WESTLEFTNO 1 WIRE MILL BUILDING 4 (1871) RIGHTNO 3 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW WEST-LEFT-NO 1 WIRE MILL BUILDING 4 (1871) RIGHT-NO 3 WIRE MILL BUILDING 9 (1876) - John A. Roebling's Sons Company & American Steel & Wire Company, South Broad, Clark, Elmer, Mott & Hudson Streets, Trenton, Mercer County, NJ

  6. VIEW OF APALACHICOLA RIVER BRIDGE SPANS 1, 2, 3, 4, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF APALACHICOLA RIVER BRIDGE SPANS 1, 2, 3, 4, AND 5, EAST SIDE, FROM SOUTH SHORE OF RIVER (LIBERTY COUNTY SIDE), FACING WEST - Apalachicola River Bridge, State Route 20 spanning the Apalachicola River, Blountstown, Calhoun County, FL

  7. Methods of using (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid

    DOEpatents

    Silverman, Richard B; Dewey, Stephen L; Miller, Steven

    2015-03-03

    (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid also known as CPP-115 or its pharmaceutically acceptable salts can be used to treat addiction and neurological disorders such as epilepsy without side effects such as visual field defects caused by vigabatrin (Sabril).

  8. Copolyimides Prepared from 3,4'-Oxydianiline and 1,3-Bis(3-Aminophenoxy) Benzene with 3,3', 4,4'-Biphenylcarboxylic Dianhydride

    NASA Technical Reports Server (NTRS)

    Jensen, Brian J. (Inventor)

    1999-01-01

    Polyimide copolymers were prepared by reacting different ratios of 3,4'-oxydianiline (ODA) and 1,3-bis(3- aminophenoxy)benzene (APB) with 3,3',4,4'- biphenylcarboxylic dianhydride (BPDA) and endcappfng with an effective amount of a non-reactive endcapper. Within a narrow ratio of diamines, from -50% ODA/50% APB to -95% ODA/5% APB, the copolyimides prepared with BPDA have a unique combination of properties that make them very attractive for various applications. This unique combination of properties includes low pressure processing (200 psi and below), long term melt stability (several hours at 390 C.), improved toughness, improved solvent resistance, improved adhesive properties, and improved composite mechanical properties.

  9. 10 CFR 960.3-1-4-1 - Site identification as potentially acceptable.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Site identification as potentially acceptable. 960.3-1-4-1 Section 960.3-1-4-1 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-1 Site...

  10. 10 CFR 960.3-1-4-1 - Site identification as potentially acceptable.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Site identification as potentially acceptable. 960.3-1-4-1 Section 960.3-1-4-1 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-1 Site identification as potentially acceptable. The...

  11. 10 CFR 960.3-1-4-1 - Site identification as potentially acceptable.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Site identification as potentially acceptable. 960.3-1-4-1 Section 960.3-1-4-1 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-1 Site identification as potentially acceptable. The...

  12. 10 CFR 960.3-1-4-1 - Site identification as potentially acceptable.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Site identification as potentially acceptable. 960.3-1-4-1 Section 960.3-1-4-1 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-1 Site identification as potentially acceptable. The...

  13. Method for preparation of 7-hydroxy-1,2,3,4-tetrahydroquinoline from 1,2,3,4-tetrahydroquinoline

    DOEpatents

    Field, George; Hammond, Peter R.

    1994-01-01

    Methods for the efficient preparation of 7-hydroxy-1,2,3,4-tetrahydroquinoline include a first method in which the acylation of m-aminophenol obtains a lactam which is reduced to give the desired quinoline and a second method in which tetrahydroquinoline is nitrated and hydrogenated and then hydrolyzed to obtain the desire quinoline. 7-hydroxy-1,2,3,4-tetrahydroquinoline is used in the efficient synthesis of four lasing dyes of the rhodamine class.

  14. Method for preparation of 7-hydroxy-1,2,3,4-tetrahydroquinoline from 1,2,3,4-tetrahydroquinoline

    DOEpatents

    Field, G.; Hammond, P.R.

    1994-02-01

    Methods for the efficient preparation of 7-hydroxy-1,2,3,4-tetrahydroquinoline include a first method in which the acylation of m-aminophenol obtains a lactam which is reduced to give the desired quinoline and a second method in which tetrahydroquinoline is nitrated and hydrogenated and then hydrolyzed to obtain the desire quinoline. 7-hydroxy-1,2,3,4-tetrahydroquinoline is used in the efficient synthesis of four lasing dyes of the rhodamine class.

  15. 3-(2-Fluoro-phen-yl)-6-(phenoxy-meth-yl)-1,2,4-triazolo[3,4-b][1,3,4]thia-diazole.

    PubMed

    Holm, Melanie; Schollmeyer, Dieter; Laufer, Stefan

    2008-01-01

    The crystal structure of the title compound, C(16)H(11)FN(4)OS, was synthesized in the course of our studies on 1,2,4-triazolo[3,4-b][1,3,4]thia-diazo-les as inhibitors of p38 mitogen-activated protein kinase (MAPK). The three-dimensional data obtained were used to generate a three-dimensional pharmacophore model for in silico database screening. The dihedral angles between the central heterocylic system and the fluoro-phenyl and phenyl rings are 20.21 (3) and 5.43 (1)°, respectively; the dihedral angle between the two benzene rings is 15.80 (4)°. PMID:21202091

  16. Indiana Reading List. [Levels 1, 2, 3, and 4].

    ERIC Educational Resources Information Center

    Indiana State Dept. of Education, Indianapolis.

    This reading list is designed as a companion piece to Indiana's Academic Standards in English/Language Arts and is organized on four levels: Level 1, Grades K-2; Level 2, Grades 3-5; Level 3, Grades 6-8; and Level 4, Grades 9-12. It contains titles and authors for approximately 800 works. The Level 1 Reading List contains these sections: fiction…

  17. 4-[4-(4-Amino-1,2,5-oxadiazol-3-yl)-1,2,5-oxadiazol-3-yl]-1,2,5-oxadiazol-3-amine

    PubMed Central

    Jia, Si-Yuan; Wang, Bo-Zhou; Fan, Xue-Zhong; Li, Ping; Ng, Seik Weng

    2012-01-01

    The complete molecule of the compound, C6H4N8O3, is generated by a crystallographic twofold rotation axis that runs through the central ring. The flanking ring is twisted by 20.2 (1)° with respect to the central ring. One of the amino H atoms forms an intra­molecular N—H⋯N hydrogen bond; adjacent mol­ecules are linked by N—H⋯N hydrogen bonds forming a chain running along [10-2]. PMID:22590430

  18. 3,4,6-Trimethyl-1-phenyl-1H-pyrazolo­[3,4-b]pyridine

    PubMed Central

    Hamri, Salha; Hafid, Abderrafia; Zouihri, Hafid; Lazar, Saïd; Khouili, Mostafa

    2010-01-01

    In the title compound, C15H15N3, the 1H-pyrazolo­[3,4-b]pyridine system and the phenyl ring are each individually planar, with r.m.s. deviations of 0.017 (2) and 0.011 (2) Å, respectively; the dihedral angle between the two aromatic systems is 9.33 (10)°. The crystal packing is stabilized by offset π–π stacking between parallel pyrazolo­[3,4-b]pyridine ring systems [face-to-face distance = 3.449 (6) Å]. PMID:21588287

  19. Anxiety Self Report (ASR (1,2,3,4,). X

    ERIC Educational Resources Information Center

    Parsons, Jane S.

    The Anxiety Self Report (ASR 1,2,3,4) is provided, followed by information about the report. The ASR is discussed as to its development, description, response bias, scoring procedures, reliability, stability, validity, and correlation between the ASR and the Manifest Anxiety Scale. (For related documents, see TM 002 928, 929.) (DB)

  20. Photoinduced 1,2,3,4-tetrahydropyridine ring conversions.

    PubMed

    Turovska, Baiba; Lund, Henning; Lūsis, Viesturs; Lielpētere, Anna; Liepiņš, Edvards; Beljakovs, Sergejs; Goba, Inguna; Stradiņš, Jānis

    2015-01-01

    Stable heterocyclic hydroperoxide can be easily prepared as a product of fast oxidation of a 1,2,3,4-tetrahydropyridine by (3)O2 if the solution is exposed to sunlight. The driving force for the photoinduced electron transfer is calculated from electrochemical and spectroscopic data. The outcome of the reaction depends on the light intensity and the concentration of O2. In the solid state the heterocyclic hydroperoxide is stable; in solution it is involved in further reactions. PMID:26664638

  1. Photoinduced 1,2,3,4-tetrahydropyridine ring conversions

    PubMed Central

    Lund, Henning; Lūsis, Viesturs; Lielpētere, Anna; Liepiņš, Edvards; Beljakovs, Sergejs; Goba, Inguna; Stradiņš, Jānis

    2015-01-01

    Summary Stable heterocyclic hydroperoxide can be easily prepared as a product of fast oxidation of a 1,2,3,4-tetrahydropyridine by 3O2 if the solution is exposed to sunlight. The driving force for the photoinduced electron transfer is calculated from electrochemical and spectroscopic data. The outcome of the reaction depends on the light intensity and the concentration of O2. In the solid state the heterocyclic hydroperoxide is stable; in solution it is involved in further reactions. PMID:26664638

  2. THE BARRIERS TO RING ROTATION IN 1,1' ,4,4'-TETRA-t-BUTYLURANOCENE AND 1,1', 3,3'-TETRA-t-BUTYLFERROCENE

    SciTech Connect

    Luke, Wayne D.; Streitwieser, Jr., Andrew

    1980-10-01

    The {sup 1}H-NMR spectra of 1,1',4,4'~tetra-t~butyluranocene show a singlet for the t~butyl protons and three singlets for the ring protons. Coalescence occurs at -65 to -85°C with splitting of each peak at lower temperatures, corresponding to {Delta}G{sup {ne}} of rotation of 8.3 Kcal mol{sup -1} Coalescence was also observed for 1,1' ,3,3'- tetra-t~butylferrocene and a corresponding {Delta}G{sup {ne}} = 13.1 Kcal mol{sup 1} was obtained.

  3. Synthesis and anticancer evaluation of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles, 1,2,4-triazoles and Mannich bases.

    PubMed

    Megally Abdo, Nadia Youssef; Kamel, Mona Monir

    2015-01-01

    A series of 5-(pyridin-4-yl)-N-substituted-1,3,4-oxadiazol-2-amines (3a-d), 5-(pyridin-4-yl)-N-substituted-1,3,4-thiadiazol-2-amines (4a-d) and 5-(pyridin-4-yl)-4-substituted-1,2,4-triazole-3-thiones (5a-d) were obtained by the cyclization of hydrazinecarbothioamide derivatives 2a-d derived from isonicotinic acid hydrazide. Aminoalkylation of compounds 5a-d with formaldehyde and various secondary amines furnished the Mannich bases 6a-p. The structures of the newly synthesized compounds were confirmed on the basis of their spectral data and elemental analyses. All the compounds were screened for their in vitro anticancer activity against six human cancer cell lines and normal fibroblast cells. Sixteen of the tested compounds exhibited significant cytotoxicity against most cell lines. Among these derivatives, the Mannich bases 6j, 6m and 6p were found to exhibit the most potent activity. The Mannich base 6m showed more potent cytotoxic activity against gastric cancer NUGC (IC50=0.021 µM) than the standard CHS 828 (IC50=0.025 µM). Normal fibroblast cells WI38 were affected to a much lesser extent (IC50>10 µM). PMID:25948330

  4. 49 CFR 173.64 - Exceptions for Division 1.3 and 1.4 fireworks.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Exceptions for Division 1.3 and 1.4 fireworks. 173... § 173.64 Exceptions for Division 1.3 and 1.4 fireworks. (a) Notwithstanding the requirements of § 173.56(b), Division 1.3 and 1.4 fireworks (see § 173.65 for Division 1.4G consumer fireworks) may...

  5. 49 CFR 173.64 - Exceptions for Division 1.3 and 1.4 fireworks.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Exceptions for Division 1.3 and 1.4 fireworks. 173... § 173.64 Exceptions for Division 1.3 and 1.4 fireworks. (a) Notwithstanding the requirements of § 173.56(b), Division 1.3 and 1.4 fireworks (see § 173.65 for Division 1.4G consumer fireworks) may...

  6. Synthesis and crystal structure of 2-(4-hydroxyphenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol

    NASA Astrophysics Data System (ADS)

    Li, S.-J.; Shen, D.; Zhang, C.-Z.

    2015-11-01

    The title compound 2-(4-hydroxyphenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol was synthesized by the reaction of phenol with hexafluoroacetone using mesitylene as solvent and. methanesulfonic acid as catalist. The structure is determined by X-ray structure analysis. Two kinds of strong intermolecular hydrogen bonds O( Alk)-H···O( Ar)and O( Ar)-H···O( Alk) are formed in crystal. These hydrogen bonds connect the molecules into two-dimensional layers. Based on theoretical calculations of the electronic structure of the title compound, its application in fluoro-containing materials is predicted. The title compound may be employed to synthesize many organic fluoro-containing polymers, because alcoholic hydroxyl and phenolic hydroxyl are easily deprotonated.

  7. 52. EQUIPMENT HOUSE, Y&D No. 107730 Scales 1/4', 3/8', 3/4', ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    52. EQUIPMENT HOUSE, Y&D No. 107730 Scales 1/4', 3/8', 3/4', 1-1/2' and 3' = 1'; July 2, 1929 - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  8. New 1-(3-nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines: synthesis and computational study.

    PubMed

    Kosychova, Lidija; Karalius, Antanas; Staniulytė, Zita; Sirutkaitis, Romualdas Aleksas; Palaima, Algirdas; Laurynėnas, Audrius; Anusevičius, Žilvinas

    2015-01-01

    Triazole derivatives constitute an important group of heterocyclic compounds have have been the subject of extensive study in the recent past. These compounds have shown a wide range of biological and pharmacological activities. In this work, new fused tricyclic 1-(3-nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]-benzodiazepines have been synthesized by the thermal cyclization of N'-(2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-3-nitrobenzohydrazides. After screening ethanol, toluene and 1-butanol as solvents, butanol-1 was found to be the best choice for the cyclization reaction in order to obtain the highest yields of tricyclic derivatives. The chemical structures of the synthesized compounds were elucidated by the analysis of their IR, 1H- and 13C-NMR spectral data. For tentative rationalization of the reaction processes, the global and local reactivity indices of certain compounds, taking part in the reaction pathway, were assessed by means of quantum mechanical calculations using the conceptual density functional theory (DFT) approach. This work could be useful for the synthesis of new heterocyclic compounds bearing a fused triazole ring. PMID:25822079

  9. Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

    SciTech Connect

    Lai, Peng-Yeh; Tsai, Chong-Bin; Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 600, Taiwan, ROC ; Tseng, Min-Jen

    2013-01-18

    Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.

  10. Synthesis and antimicrobial activity of some novel fused heterocyclic 1,2,4-triazolo [3,4-b][1,3,4] thiadiazine derivatives

    PubMed Central

    Sahu, Jagdish K.; Ganguly, Swastika; Kaushik, Atul

    2014-01-01

    In the present investigation, the synthesis and antimicrobial evaluation of 1,2,4-triazolo [3,4-b][1,3,4] thiadiazine including different pharmacophores are aimed at. In this study, a series of 6-aryl-3- (3,4 -dialkoxyphenyl)-7H -[1,2,4]triazolo [3,4-b][1,3,4] thiadiazine (7a-7k) was synthesized by condensing 4-amino-5-(3,4-dialkoxyphenyl)-4H-[1,2,4]- triazole-3-thiol (6) with various aromatic carboxylic acids in the presence of phenacyl bromides through one-pot reaction. Eleven fused heterocyclic derivatives were successfully synthesized. The structures of these newly synthesized compounds were characterized by IR, 1H NMR and mass spectroscopic studies. All the synthesized compounds were screened for their antimicrobial evaluation. Some of the compounds exhibited promising antimicrobial activity. From the present study it may be concluded that synthesized compounds are fruitful in terms of their structural novelty and marked biological activities. These compounds could be further modified to develop potential and safer antifungal agents. PMID:24959418

  11. 1,3-Bis[(4-methylbenzylidene)amino-oxy]propane.

    PubMed

    Wu, Jian-Chao; Gao, Su-Xia; Dong, Wen-Kui; Tong, Jun-Feng; Li, Li

    2009-01-01

    The title bis-oxime compound, C(19)H(22)N(2)O(2), synthesized by the reaction of 4-methyl-2-hydroxy-benzaldehyde with 1,3-bis-(amino-oxy)propane in ethanol, adopts a V-shaped conformation. The dihedral angle between the rings is 84.59 (3)°. The mol-ecule is disposed about a crystallographic twofold rotation axis, with one C atom lying on the axis. In the crystal, mol-ecules are packed by C-H⋯π(Ph) inter-actions, forming chains. PMID:21578377

  12. Enhanced HIV-1 neutralization by a CD4-VH3-IgG1 fusion protein

    SciTech Connect

    Meyuhas, Ronit; Noy, Hava; Fishman, Sigal; Margalit, Alon; Montefiori, David C.; Gross, Gideon

    2009-08-21

    HIV-1 gp120 is an alleged B cell superantigen, binding certain VH3+ human antibodies. We reasoned that a CD4-VH3 fusion protein could possess higher affinity for gp120 and improved HIV-1 inhibitory capacity. To test this we produced several human IgG1 immunoligands harboring VH3. Unlike VH3-IgG1 or VH3-CD4-IgG1, CD4-VH3-IgG1 bound gp120 considerably stronger than CD4-IgG1. CD4-VH3-IgG1 exhibited {approx}1.5-2.5-fold increase in neutralization of two T-cell laboratory-adapted strains when compared to CD4-IgG1. CD4-VH3-IgG1 improved neutralization of 7/10 clade B primary isolates or pseudoviruses, exceeding 20-fold for JR-FL and 13-fold for Ba-L. It enhanced neutralization of 4/8 clade C viruses, and had negligible effect on 1/4 clade A pseudoviruses. We attribute this improvement to possible pairing of VH3 with CD4 D1 and stabilization of an Ig Fv-like structure, rather than to superantigen interactions. These novel findings support the current notion that CD4 fusion proteins can act as better HIV-1 entry inhibitors with potential clinical implications.

  13. New 2-aryl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-4-one derivatives as diuretics.

    PubMed

    Monge, A; Martinez-Merino, V; Simon, M A; Sanmartin, C

    1993-12-01

    2-Aryl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-4-one derivatives having various substituents at the 4'-position, H or methyl at 1,3-positions and nitro or amino at 6-position were prepared and tested for their diuretic, natriuretic and kaliuretic activities on male Wistar rats at a dosage of 25 mg/kg or less. 2-(3-Pyridyl) derivatives were inactive. 1,3-Dimethyl-6-nitro-2-phenyl derivatives (1) were active depending on the electronic character of the 4'-substituent but at the same time were sodium-sparing. However, 1(H),3(H)-6-nitro-2-phenyl derivatives (2) were generally inactive as diuretics but active as potassium-sparing drugs. 6-Amino-1(H),3(H)-2-phenyl derivatives (4) were active as diuretics depending on dipolar moment of the substituent at the 4'-position, and induced moderate potassium release. The 6-amino-2-(4-trifluoromethylphenyl)-1, 2,3,4-tetrahydropyrido [2,3-d]pyrimidin-4-one (4f) remained active up to a dosage of 3 mg/kg. The structure-activity relationships were carried out in light of the adaptative least squares (ALS) method and discriminant functions for diuretic compounds were established. PMID:8141821

  14. A Palladium-Catalyzed Method for the Synthesis of 2-(α-Styryl)-2,3-dihydroquinazolin-4-ones and 3-(α-Styryl)-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide: Access to 2-(α-Styryl)quinazolin-4(3H)-ones and 3-(α-Styryl)-1,2,4-benzothiadiazine-1,1-dioxides.

    PubMed

    Kundu, Priyanka; Mondal, Amrita; Chowdhury, Chinmay

    2016-08-01

    An efficient synthesis of 2-(α-styryl)-2,3-dihydroquinazolin-4-ones and 3-(α-styryl)-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxides has been achieved in 39-94% yield through palladium-catalyzed cyclocondensation of aryl/vinyl iodides with allenamides 13-15 and 22, respectively. Base treatment of the N-tosylated products provides an easy access to 2-(α-styryl)quinazolin-4(3H)-ones and 3-(α-styryl)-1,2,4-benzothiadiazine-1,1-dioxides, hitherto unknown heterocycles. The method has been tested with phenyl substituted allenamides, applied for bis-heteroannulation, and used in the preparation of analogues of the natural product Luotonin F. PMID:27454621

  15. 4,4′-(Propane-1,3-di­yl)dipiperidinium sulfate monohydrate

    PubMed Central

    Yang, E; Song, Xu-Chun; Zhuang, Rong-Qiang

    2008-01-01

    In the title compound, C13H28N2 2+·SO4 2−·H2O, extensive hydrogen-bonding inter­actions between the protonated 4,4′-(propane-1,3-di­yl)dipiperidinium ions, the sulfate anions and the water mol­ecules lead to a three-dimensional pillared and layered structure with the 4,4′-(propane-1,3-di­yl)­dipiperidinium ions acting as the pillars. PMID:21201745

  16. Equilibration in φ4 theory in 3+1 dimensions

    NASA Astrophysics Data System (ADS)

    Arrizabalaga, Alejandro; Smit, Jan; Tranberg, Anders

    2005-07-01

    The process of equilibration in φ4 theory is investigated for a homogeneous system in 3+1 dimensions and a variety of out-of-equilibrium initial conditions, both in the symmetric and broken phase, by means of the 2PI effective action. Two Φ-derivable approximations including scattering effects are used: the two-loop and the basketball, the latter corresponding to the truncation of the 2PI effective action at O(λ2). The approach to equilibrium, as well as the kinetic and chemical equilibration is investigated.

  17. Investigation of rocket motors 3 inch number 1 Mk 4

    NASA Astrophysics Data System (ADS)

    Barrington, L. M.

    1994-05-01

    In 1992, Aircraft Research and Development Unit (ARDU), RAAF, experienced two misfires with Rocket Motors, 3 in., No. 1, Mk 4, during a series of firings at Woomera. These motors were sampled from a batch manufactured in 1957, and subsequent to the misfires this batch was withdrawn from use. An alternate batch of motors manufactured in 1966 was available to ARDU. Tests were conducted on a number of these motors to advise on their suitability for use, and as a result, a further five years life was assigned with a recommendation to retest after that period.

  18. Evaluation of the oral subchronic toxicity of AHTN (7-Acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene) in the rat.

    PubMed

    Api, Anne Marie; Smith, Robert L; Pipino, Sandra; Marczylo, Timothy; De Matteis, Francesco

    2004-05-01

    7-Acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN) is used as a fragrance material in a wide variety of consumer products. Because of its widespread exposure, a 90-day oral feeding study, with 4-week recovery periods for selected rats, was conducted. AHTN was added to the diet of rats at levels calculated to result in mean daily doses of 1.5, 5, 15 or 50 mg AHTN/kg body weight/day. On completion of the treatment period, 3 males and 3 females from each of the high dose groups and controls were maintained for a treatment free period of 4 weeks. There were no adverse effects revealed upon clinical examination or following extensive histopathological examinations. Histopathological examination of the prostate, seminal vesicles, mammary gland and testes of males and ovaries, mammary gland, uterus and vagina of females, undertaken on all animals in all test groups, revealed no evidence of hormonal effects of AHTN. A statistically significant decrease in body weight gain was observed in both sexes in the high dose group only. Statistically significant effects were observed in hematology and blood chemistry, although these effects were all within the range for historical controls and were not proportional to dose. A green to dark brown coloration in the livers and mesenteric lymph nodes was also seen in high dose animals. At the end of the treatment-free period, the color change was almost completely reversed; one high dose male still had green colored lymph nodes, but the liver appeared normal. A green coloration of the lacrimal glands in females, but not males, was also seen in 8/12, 4/15 and in 1 female given 50, 15 and 5 mg/kg body weight/day, respectively. This green color was still present in 2/3 of the high dose females after the treatment-free period. Microscopic examination of unstained sections of frozen livers under UV illumination did not reveal any fluorescence that might have been consistent with porphyrin accumulation. These findings were

  19. 5-(3,4-Dimethyl-benzyl-idene)-2,2-dimethyl-1,3-dioxane-4,6-dione.

    PubMed

    Zeng, Wu-Lan

    2011-06-01

    The title compound, C(15)H(16)O(4), was prepared by the reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione and 3,4-dimethyl-benzaldehyde in ethanol. The 1,3-dioxane ring exhibits an envelope conformation. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds, forming chains parallel to the b axis. PMID:21754745

  20. Bis(4H-1,2,4-triazol-3-yl)disulfane

    PubMed Central

    Liu, Dongsheng; Xu, Yaping; Li, Xinfa; Ying, Shaoming; Chen, Wentong

    2008-01-01

    The title compound, C4H4N6S2, was synthesized by the reaction of 3-mercapto-1H-1,2,4-triazole with sodium hydrox­ide in ethanol. The mol­ecule possesses a crystallographically imposed twofold axis. Inter­molecular N—H⋯N hydrogen bonds link the mol­ecules into chains along the c axis. PMID:21200812

  1. Synthesis and structural study on heterocyclic compounds 7-decanoyloxy-3-(4‧-substitutedphenyl)-4H-1-benzopyran-4-ones: Crystal structure of 7-decanoyloxy-3-(4‧-methylphenyl)-4H-1-benzopyran-4-one

    NASA Astrophysics Data System (ADS)

    Yeap, Guan-Yeow; Yam, Wan-Sinn; Dominiak, Paulina; Ito, Masato M.

    2010-04-01

    Six new isoflavone-based esters, 7-decanoyloxy-3-(4'-substitutedphenyl)-4 H-1-benzopyran-4-ones, derived from 1,3-benzenediol (resorcinol) and different para substituted phenylacetic acids have been synthesized and characterized. The molecular structures of the title compounds were elucidated with the employment of physical measurements and spectroscopic techniques (FTIR, 1D and 2D NMR). The conformation of 7-decanoyloxy-3-(4'-methylphenyl)-4 H-1-benzopyran-4-one was determined by single crystal X-ray diffraction analysis of which the title compound crystallized into triclinic lattice with P-1 space group. Crystal structure of the title compound also revealed that the two phenyl rings of the central moiety were planar whilst the heterocyclic ring was found to pucker slightly from the mean plane.

  2. Structural basis of the impact sensitivities of 1-picryl-1,2,3-triazole, 2-picryl-1,2,3-triazole, 4-nitro-1-picryl-1,2,3-triazole, and 4-nitro-2-picryl-1,2,3-triazole

    SciTech Connect

    Storm, C.B.; Ryan, R.R.; Ritchie, J.P.; Hall, J.H.; Bachrach, S.M. )

    1989-01-26

    The isomeric pairs 1-picryl-1,2,3-triazole, 2-picryl-1,2,3-triazole and 4-nitro-1-picryl-1,2,3-triazole, 4-nitro-1-picryl-1,2,3-triazole differ dramatically in their impact sensitivity. Since these pairs of compounds have identical oxygen balance this strongly suggests that there is a difference in the decomposition mechanism. The authors report here the x-ray crystal structure, molecular orbital calculations, and {sup 13}C and {sup 1}H NMR spectra of the four compounds. The picryl substituents are essentially identical in all four cases. The most significant structural difference in the X-ray structures and in the molecular orbital calculations is a decrease in the N2-N3 bond length, accompanied by a lengthening of the adjacent bonds, in the two 1-picryl isomers relative to the corresponding bond lengths in the 2-picryl isomers. Molecular orbital calculations show that this leads to a low activation energy for the elimination of N{sub 2} from the 1-picryl isomers. They suggest that this initial step then leads to a reactive intermediate and is responsible for the large difference in sensitivity.

  3. Metabolism of 1,2,3,4-, 1,2,3,5-, and 1,2,4,5-tetrachlorobenzene in the squirrel monkey

    SciTech Connect

    Schwartz, H.; Chu, I.; Villeneuve, D.C.; Benoit, F.M.

    1987-01-01

    The metabolism of three tetrachlorobenzene isomers (TeCB) was investigated in the squirrel monkey. The animals were administered orally 6 single doses of /sup 14/C-labeled 1,2,3,4-, 1,2,4,5-, or 1,2,3,5-tetrachlorobenzene over a 3-wk period at levels ranging from 50 to 100 mg/kg body weight (b.w) and kept in individual metabolism cages to collect urine and feces for radioassay. Approximately 38% (1,2,3,4-TeCB), 36% (1,2,3,5-TeCB), and 18% (1,2,4,5-TeCB) of the doses were excreted respectively in the feces 48 h post administration. In monkeys dosed with 1,2,3,4-TeCB, unchanged compound accounted for 50% of the fecal radioactivity. Unchanged compound accounted for more than 50% of the fecal radioactivity found in the monkeys dosed with 1,2,3,5-TeCB. The fecal metabolites were identified in both groups. No metabolites were detected in the feces of monkeys dosed with 1,2,4,5-TeCB. While the fecal route represented the major route of excretion for 1,2,3,4-TeCB, the other two isomers were eliminated exclusively in the feces. The above data in the squirrel monkey are different from those obtained with the rat and the rabbit, and demonstrate the different metabolic pathways for the isomers.

  4. 5-(Adamantan-1-yl)-3-(benzyl­sulfan­yl)-4-methyl-4H-1,2,4-triazole

    PubMed Central

    Al-Abdullah, Ebtehal S.; El-Emam, Ali A.; Ghabbour, Hazem A.; Chantrapromma, Suchada; Fun, Hoong-Kun

    2012-01-01

    In the asymmetric unit of the title adamantyl derivative, C20H25N3S, there are two crystallographic independent mol­ecules with slightly different conformations. In one mol­ecule, the whole benzyl group is disordered over two orientations with the refined site-occupancy ratio of 0.63 (2):0.37 (2). The dihedral angles between the 1,2,4-triazole and phenyl rings are 24.3 (8) (major component) and 25.8 (13)° (minor component) in the disordered mol­ecule, whereas the corresponding angle is 51.53 (16)° in the other mol­ecule. In the crystal, mol­ecules are linked into a chain along the a axis by a weak C—H⋯N inter­action. Weak C—H⋯π inter­actions are also observed. PMID:22904878

  5. Crystal structure of 1-[2,4-bis(4-methoxy­phenyl)-3-azabicyclo[3.3.1]nonan-3-yl]ethanone

    PubMed Central

    Shreevidhyaa Suressh, V.; Sathya, S.; Akila, A.; Ponnuswamy, S.; Usha, G.

    2014-01-01

    In the title compound, C24H29NO3, the aza­bicycle contains two six-membered rings, viz. a cyclo­hexane ring and a piperidine ring. The first adopts a chair conformation and the second a half-chair conformation. The dihedral angle between their mean planes is 86.21 (13)°, indicating that they are almost perpendicular to one another. The dihedral angle between the planes of the 4-meth­oxy­phenyl rings is 17.51 (13)°, and they make dihedral angles of 81.9 (3) and 81.3 (3)° with the ethan-1-one group. In the crystal, mol­ecules are linked by C—H⋯π inter­actions forming chains along [10-1]. PMID:25484811

  6. Synthesis and fluorescence properties of 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazol derivatives and their terbium complexes.

    PubMed

    Zhang, Wu; Chai, Yuchao; Li, Kangyun; Chen, Yanwen; Yan, Dong; Guo, Dongcai

    2014-12-01

    Eight novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazol derivatives have been designed and synthesized, and their corresponding Tb(3+) complexes were also prepared successfully. The fluorescence properties and fluorescence quantum yields of the target complexes were investigated, the results showed that the ligands were an efficient sensitizer for Tb(3+) luminescence, and the target complexes exhibited characteristic fluorescence emissions of Tb(3+) ion. The fluorescence intensity of the complex substituted by chlorine was stronger than that of other complexes. The substituents' nature has a great effect upon the electrochemical properties of the target complexes. The results showed that the introduction of the electron-withdrawing groups tended to decrease the oxidation potential and highest occupied molecular orbital energy levels of the target Tb(3+) complexes; however, introduction of the electron-donating groups can increase the corresponding complexes' oxidation potential and highest occupied molecular orbital energy levels. PMID:24846775

  7. Preparation of 3,3'-azobis(6-amino-1,2,4,5-tetrazine)

    DOEpatents

    Hiskey, Michael A.; Chavez, David E.; Naud, Darren

    2002-01-01

    The compound of the structure ##STR1## where a, b, c, d and e are 0 or 1 and a+b+c+d+e is from 0 to 5 is disclosed together with the species 3,3'-azobis(6-amino-1,2,4,5-tetrazine) and a process of preparing such compounds.

  8. PP1α, PP1β and Wip-1 regulate H4S47 phosphorylation and deposition of histone H3 variant H3.3

    PubMed Central

    Zhang, Hui; Wang, Zhiquan; Zhang, Zhiguo

    2013-01-01

    Phosphorylation of histone H4 serine 47 (H4S47ph) is catalyzed by Pak2, a member of the p21-activated serine/threonine protein kinase (Pak) family and regulates the deposition of histone variant H3.3. However, the phosphatase(s) involved in the regulation of H4S47ph levels was unknown. Here, we show that three phosphatases (PP1α, PP1β and Wip1) regulate H4S47ph levels and H3.3 deposition. Depletion of each of the three phosphatases results in increased H4S47ph levels. Moreover, PP1α, PP1β and Wip1 bind H3-H4 in vitro and in vivo, whereas only PP1α and PP1β, but not Wip1, interact with Pak2 in vivo. These results suggest that PP1α, PP1β and Wip1 regulate the levels of H4S47ph through directly acting on H4S47ph, with PP1α and PP1β also likely regulating the activity of Pak2. Finally, depletion of PP1α, PP1β and Wip1 leads to increased H3.3 occupancy at candidate genes tested, elevated H3.3 deposition and enhanced association of H3.3 with its chaperones HIRA and Daxx. These results reveal a novel role of three phosphatases in chromatin dynamics in mammalian cells. PMID:23828041

  9. 40 CFR 721.10379 - Propanoic acid, 3-(dodecylthio)-, 2-(1,1-dimethylethyl)-4-[[5-(1,1-dimethylethyl)-4-hydroxy-2...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...,1-dimethylethyl)-4- thio]-5-methylphenyl ester. 721.10379 Section 721.10379 Protection of...-(dodecylthio)-, 2-(1,1-dimethylethyl)-4- thio]-5-methylphenyl ester. (a) Chemical substance and significant new...-(1,1-dimethylethyl)-4- thio]-5-methylphenyl ester (PMN P-10-266; CAS No. 69075-62-3) is subject...

  10. 40 CFR 721.10379 - Propanoic acid, 3-(dodecylthio)-, 2-(1,1-dimethylethyl)-4-[[5-(1,1-dimethylethyl)-4-hydroxy-2...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...,1-dimethylethyl)-4- thio]-5-methylphenyl ester. 721.10379 Section 721.10379 Protection of...-(dodecylthio)-, 2-(1,1-dimethylethyl)-4- thio]-5-methylphenyl ester. (a) Chemical substance and significant new...-(1,1-dimethylethyl)-4- thio]-5-methylphenyl ester (PMN P-10-266; CAS No. 69075-62-3) is subject...

  11. 40 CFR 721.10379 - Propanoic acid, 3-(dodecylthio)-, 2-(1,1-dimethylethyl)-4-[[5-(1,1-dimethylethyl)-4-hydroxy-2...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...,1-dimethylethyl)-4- thio]-5-methylphenyl ester. 721.10379 Section 721.10379 Protection of...-(dodecylthio)-, 2-(1,1-dimethylethyl)-4- thio]-5-methylphenyl ester. (a) Chemical substance and significant new...-(1,1-dimethylethyl)-4- thio]-5-methylphenyl ester (PMN P-10-266; CAS No. 69075-62-3) is subject...

  12. The antiobesity factor WDTC1 suppresses adipogenesis via the CRL4WDTC1 E3 ligase.

    PubMed

    Groh, Beezly S; Yan, Feng; Smith, Matthew D; Yu, Yanbao; Chen, Xian; Xiong, Yue

    2016-05-01

    WDTC1/Adp encodes an evolutionarily conserved suppressor of lipid accumulation. While reduced WDTC1 expression is associated with obesity in mice and humans, its cellular function is unknown. Here, we demonstrate that WDTC1 is a component of a DDB1-CUL4-ROC1 (CRL4) E3 ligase. Using 3T3-L1 cell culture model of adipogenesis, we show that disrupting the interaction between WDTC1 and DDB1 leads to a loss of adipogenic suppression by WDTC1, increased triglyceride accumulation and adipogenic gene expression. We show that the CRL4(WDTC) (1) complex promotes histone H2AK119 monoubiquitylation, thus suggesting a role for this complex in transcriptional repression during adipogenesis. Our results identify a biochemical role for WDTC1 and extend the functional range of the CRL4 complex to the suppression of fat accumulation. PMID:27113764

  13. Synthesis, antitumor evaluation and 3D-QSAR studies of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives.

    PubMed

    Xu, Feng; Yang, Zhen-Zhen; Ke, Zhong-Lu; Xi, Li-Min; Yan, Qi-Dong; Yang, Wei-Qiang; Zhu, Li-Qing; Lin, Fei-Lei; Lv, Wei-Ke; Wu, Han-Gui; Wang, John; Li, Hai-Bo

    2016-10-01

    A series of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives have been synthesized and their structures were confirmed by single-crystal X-ray diffraction. Compared to some reported structures of 1,6-dihydro-1,2,4,5-tetrazine, these compounds can't be considered as having homoaromaticity. Their antiproliferative activities were evaluated against MCF-7, Bewo and HL-60 cells in vitro. Two compounds were highly effective against MCF-7, Bewo and HL-60 cells with IC50 values in 0.63-13.12μM. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out on 51 [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives with antiproliferative activity against MCF-7 cell. Models with good predictive abilities were generated with the cross validated q(2) values for CoMFA and CoMSIA being 0.716 and 0.723, respectively. Conventional r(2) values were 0.985 and 0.976, respectively. The results provide the tool for guiding the design and synthesis of novel and more potent tetrazine derivatives. PMID:27597251

  14. Primary structure of the (13,14)-β-D-glucan 4-glucohydrolase from barley aleurone

    PubMed Central

    Fincher, Geoffrey B.; Lock, Peter A.; Morgan, Margaret M.; Lingelbach, Klaus; Wettenhall, Richard E. H.; Mercer, Julian F. B.; Brandt, Anders; Thomsen, Karl Kristian

    1986-01-01

    During germination of barley grains, the cell walls of the starchy endosperm are degraded by (13,14)-β-glucanases (EC 3.2.1.73) secreted from the aleurone and scutellar tissues. The complete sequence of the aleurone (13,14)-β-glucanase isoenzyme II comprises 306 amino acids and was determined by sequencing nine tryptic peptides (110 residues) and aligning them with the amino acid sequence deduced from a cDNA clone encoding the 291 NH2-terminal residues. Although no amino acid sequence homology with a bacterial (13)(14)-β-glucanase is apparent, close to 50% homology is found with two large regions of a (13)-β-glucanase from tobacco pith tissue. The gene for barley (13,14)-β-glucanase isoenzyme II shares with that for the α-amylase isoenzyme 1 a strongly preferred use of codons with G and C in the wobble position (94% and 90%, respectively). Both enzymes are secreted from the aleurone cells during germination. Such one-sided codon usage is not characteristic for the gene encoding the (13)-β-glucanase of tobacco pith tissue or the hor2-4 gene encoding the B1 hordein storage protein in the endosperm. Images PMID:16593676

  15. Synthesis and characterization of new 1,4 and 1,5-disubstituted glucopyranosyl 1,2,3-triazole by 1,3-dipolar cycloaddition

    NASA Astrophysics Data System (ADS)

    El Moncef, Abdelkarim; El Hadrami, El Mestafa; Ben-Tama, Abdeslem; de Arellano, Carmen Ramírez; Zaballos-Garcia, Elena; Stiriba, Salah-Eddine

    2009-07-01

    A series of 1,4 and 1,5-disubstituted 1-(β- D-glucopyranosyl)-1,2,3-triazoles has been prepared in an efficient manner with excellent yields using the intermolecular 1,3-dipolar cycloaddition of 1-azido-2,3,4,6-tetra- O-acetyl-β- D-glucopyranose 2 to a variety of substituted alkynes phenylacethylene 3, propargyl alcohol 4, 2-butyn-1,4-diol, 5, 3-propargylbenzimidazole 6 and propargylpyrazole 7 in toluene. The reaction takes place with the formation of both 4- and 5-regioisomers.

  16. The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch.

    PubMed

    Oberst, Andrew; Malatesta, Martina; Aqeilan, Rami I; Rossi, Mario; Salomoni, Paolo; Murillas, Rodolfo; Sharma, Prashant; Kuehn, Michael R; Oren, Moshe; Croce, Carlo M; Bernassola, Francesca; Melino, Gerry

    2007-07-01

    Nedd4-binding partner-1 (N4BP1) has been identified as a protein interactor and a substrate of the homologous to E6AP C terminus (HECT) domain-containing E3 ubiquitin-protein ligase (E3), Nedd4. Here, we describe a previously unrecognized functional interaction between N4BP1 and Itch, a Nedd4 structurally related E3, which contains four WW domains, conferring substrate-binding activity. We show that N4BP1 association with the second WW domain (WW2) of Itch interferes with E3 binding to its substrates. In particular, we found that N4BP1 and p73 alpha, a target of Itch-mediated ubiquitin/proteasome proteolysis, share the same binding site. By competing with p73 alpha for binding to the WW2 domain, N4BP1 reduces the ability of Itch to recruit and ubiquitylate p73 alpha and inhibits Itch autoubiquitylation activity both in in vitro and in vivo ubiquitylation assays. Similarly, both c-Jun and p63 polyubiquitylation by Itch are inhibited by N4BP1. As a consequence, genetic and RNAi knockdown of N4BP1 diminish the steady-state protein levels and significantly impair the transcriptional activity of Itch substrates. Notably, stress-induced induction of c-Jun was impaired in N4BP1(-/-) cells. These results demonstrate that N4BP1 functions as a negative regulator of Itch. In addition, because inhibition of Itch by N4BP1 results in the stabilization of crucial cell death regulators such as p73 alpha and c-Jun, it is conceivable that N4BP1 may have a role in regulating tumor progression and the response of cancer cells to chemotherapy. PMID:17592138

  17. APOBEC3G ubiquitination by Nedd4-1 favors its packaging into HIV-1 particles.

    PubMed

    Dussart, Sylvie; Douaisi, Marc; Courcoul, Marianne; Bessou, Gilles; Vigne, Robert; Decroly, Etienne

    2005-01-21

    APOBEC3G is a cytidine deaminase that limits the replication of many retroviruses. This antiviral host factor is packaged into retrovirus particles, where it targets single-stranded DNA generated during reverse transcription and induces up to 2% of G-to-A mutations, which are lethal for the HIV-1 provirus. Vif protein counteracts this antiviral factor by decreasing its packaging into lentivirus particles. Here, we demonstrate that Nedd4-1, an HECT E3 ubiquitin ligase, interacts with APOBEC3G, through its WW2 and WW3 domains. As a result of this interaction, APOBEC3G undergoes post-translational modification by addition of ubiquitin moieties. Accordingly, we demonstrate that the dominant negative Nedd4-1 C/S form prevents APOBEC3G ubiquitination. Moreover, the packaging of APOBEC3G into Pr55 Gag virus-like particles and into HIV-1 virions is reduced when Nedd4-1 C/S is expressed. During HIV-1 viral production in the presence of APOBEC3G, Nedd4-1 C/S restores partially the infectivity of Deltavif HIV-1. We conclude that the ubiquitination of APOBEC3G by Nedd4-1 favors its targeting to the virus assembly site where APOBEC3G interacts with Gag and is packaged into HIV-1 particles in the absence of Vif. PMID:15581898

  18. Fluorination of 1,2,3,4- and 1,2,3,5-tetrahalobenzenes with potassium fluoride in dimethyl sulfone

    USGS Publications Warehouse

    Finger, G.C.; Dickerson, D.R.; Shiley, R.H.

    1972-01-01

    1,2,3,4-Tetrachlorobenzene, 1,2,3,5-tetrachlorobenzene, 2,4,6-trichlorofluorobenzene, and 2,6-dichloro-1,4-difluorobenzene were fluorinated with potassium fluoride and potassium fluoride-cesium fluoride mixtures in dimethyl sulfone. By varying the concentration, temperature and reaction time, the degree of fluorination could be controlled to some extent. The optimum conditions for producing mono-, di- and tri-fluoro-substituted chlorobenzenes and trace amounts of tetrafluorobenzene from the corresponding tetrachlorobenzenes are given. 1,2,3,5-Tetrafluorobenzene was obtained in 44.8% yield from 2,6-dichloro-1,4-difluorobenzene. 1,2,3,4-Tetrafluorobenzene was obtained in only trace amounts from 1,2,3,4-tetrachlorobenzene. A total of 24 new chlorofluorobenzenes and intermediates are described. Fluorination with potassium fluoride and certain other metal fluorides was also investigated. ?? 1972.

  19. Formation of inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate from inositol 1,3,4,5-tetrakisphosphate and their pathways of degradation in RBL-2H3 cells

    SciTech Connect

    Cunha-Melo, J.R.; Dean, N.M.; Ali, H.; Beaven, M.A.

    1988-10-05

    Previous studies with antigen-stimulated rat basophilic leukemia (RBL-2H3) cells indicated the formation of multiple isomers of each of the various categories of inositol phosphates. The identities of the different isomers have been elucidated by selective labeling of (3H)inositol 1,3,4,5-tetrakisphosphate with (32P)phosphate in the 3'-or 4',5'-positions and by following the metabolism of different radiolabeled inositol phosphates in extracts of RBL-2H3 cells. We report here that inositol 1,3,4,5-tetrakisphosphate, when incubated with the membrane fraction of extracts of RBL-2H3 cells, was converted to inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate. Further dephosphorylation of the inositol polyphosphates proceeded rapidly in whole extracts of cells, although the process was significantly retarded when ATP (2 mM) levels were maintained by an ATP-regenerating system. The degradation of inositol 1,4,5-trisphosphate proceeded with the sequential formation of inositol 1,4-bisphosphate, the inositol 4-monophosphate (with smaller amounts of the 1-monophosphate), and finally inositol. Inositol 1,3,4-trisphosphate, on the other hand, was converted to inositol 1,3-bisphosphate and inositol 3,4-bisphosphate and subsequently to inositol 4-monophosphate and inositol 1-monophosphate (stereoisomeric forms were undetermined). The possible implications of the apparent interconversion between inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in regulating histamine secretion in the RBL-2H3 cells are discussed.

  20. 40 CFR 721.8940 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...] amino]-4-(oxo-.kappa.O)-5- pyrimidinyl]azo-.kappaN1] -4-hydroxy-.kappa.O)-5-nitrobenzenesulfonato(3... Specific Chemical Substances § 721.8940 Chromate(3-), bis phenyl]sulfonyl] amino]-4-(oxo-.kappa.O)-5...-), bis phenyl] sulfonyl]amino]-4-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1]...

  1. 40 CFR 721.8940 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...] amino]-4-(oxo-.kappa.O)-5- pyrimidinyl]azo-.kappaN1] -4-hydroxy-.kappa.O)-5-nitrobenzenesulfonato(3... Specific Chemical Substances § 721.8940 Chromate(3-), bis phenyl]sulfonyl] amino]-4-(oxo-.kappa.O)-5...-), bis phenyl] sulfonyl]amino]-4-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1]...

  2. Comparative Characterization of Phosphoenolpyruvate Carboxylase in C3, C4, and C3-C4 Intermediate Panicum Species 1

    PubMed Central

    Holaday, A. Scott; Black, Clanton C.

    1981-01-01

    Various properties of phosphoenolpyruvate carboxylases were compared in leaf preparations from C3-C4 intermediate, C3, and C4Panicum species. Values of Vmax in micromoles per milligram chlorophyll per hour at pH 8.3 were 57 to 75 for the enzyme from Panicum milioides, Panicum schenckii, and Panicum decipiens (all C3-C4). The values for Panicum laxum (C3) and Panicum prionitis (C4) were 20 to 40 and 952 to 1374, respectively. The Vmax values did not change at pH 7.3 except for the C4 value, which increased about 24%. At pH 8.3, the phosphoenolpyruvate carboxylases from C3 and C3-C4 species had slightly higher Km HCO3− and lower K′ phosphoenolpyruvate values than did the C4 enzyme. With each species at pH 7.3, all K′ phosphoenolpyruvate values were 2- to 4-fold greater. The enzyme from all species was inhibited 85 to 90% by 1 millimolar malate at rate-limiting phosphoenolpyruvate and Mg2+ levels. With low levels of malate, 0.2 millimolar, the rate curve with respect to phosphoenolpyruvate was distinctly sigmoidal, and the inhibition was not eliminated at 5 millimolar phosphoenolpyruvate. Malate at 10 millimolar protected all phosphoenolpyruvate carboxylases from inactivation at 55 C at pH 5.5, but not at pH 8.3. Aspartate did not protect well. When incubated at 37 C at pH 8.3 without phosphoenolpyruvate, but with HCO3−, the enzyme from several C4 grasses lost 92 to 98% of the initial activity after 4 minutes, whereas the enzymes from C3 and C3-C4Panicum species retained 60 to 70% of their activities. In contrast, 5 millimolar phosphoenolpyruvate stabilized the enzyme at 37 C in all plant extracts. The phosphoenolpyruvate carboxylase from C3-C4 intermediate Panicum species has properties most similar to the enzyme from C3Panicum species. The higher leaf activity of the enzyme from the intermediate plants than from C3 species is not due to any unusual property assayed other than a higher Vmax. PMID:16661669

  3. 40 CFR 721.8950 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...]amino]-4-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1]-4-hydroxy-.kappa.O)-5-nitrobenzenesulfonato(3... substance identified as chromate(3-), bis phenyl]sulfonyl]amino]-4-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1... Significant New Uses for Specific Chemical Substances § 721.8950 Chromate(3-), bis...

  4. 40 CFR 721.8950 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...]amino]-4-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1]-4-hydroxy-.kappa.O)-5-nitrobenzenesulfonato(3... substance identified as chromate(3-), bis phenyl]sulfonyl]amino]-4-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1... Significant New Uses for Specific Chemical Substances § 721.8950 Chromate(3-), bis...

  5. 10 CFR 960.3-1-4-1 - Site identification as potentially acceptable.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Site identification as potentially acceptable. 960.3-1-4-1... as potentially acceptable. The evidence for the identification of a potentially acceptable site shall... general and less detailed than that required for the nomination of a site as suitable for...

  6. QSAR studies on 3-(4-biphenylmethyl) 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] Pyridine derivatives as angiotensin II (AT1) receptor antagonist.

    PubMed

    Sharma, Mukesh C

    2015-06-01

    QSAR studies were performed for correlating the chemical composition of 3-(4-biphenylmethyl) 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] pyridines bearing aryl acetic acid esters and acetamides as angiotensin II AT(1) receptor antagonist. Four different quantitative structure-property relationship (QSAR) methods namely two-dimensional (2D-QSAR), group-based QSAR, k-nearest neighbor and Pharmacophore Modeling were employed to obtain statistically significant models. The statistically significant best 2D-QSAR model having correlation coefficient r(2) = 0:8940 and cross-validated squared correlation coefficient q(2) = 0:7648 with external predictive ability of pred_r(2) = 0:8177,pred_r(2)se = 0.4119 and best group-based QSAR model having r(2) = 0:7392 and q(2) = 0:6710with pred_r(2) = 0:7503was developed by SA-principal component regression. The most predictive k-nearest neighbor model derived from the superposition of conformations has good cross-validated q(2) = 0:7637 and satisfied predictive ability r(2)_pred = 0.7143. Continuing with compounds of substituted 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] pyridine derivatives chemical feature-based pharmacophore models with lowest RMSD value (0.3292 Å) consists of two Hac (Hydrogen bond acceptor), negative ionizable, and two AroC (Aromatic) features are important for the activity. The study suggested that substitution of group at R, R 1, R 2 and Ar, and position on 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] pyridine ring with more electronegative nature and low bulkiness are favorable for the antihypertensive activity. These theoretical results may provide a useful reference for understanding the action mechanism and designing potential angiotensin II (AT1) receptor antagonist. PMID:26215494

  7. Synthesis and antimicrobial evaluation of novel 4-amino-6-(1,3,4-oxadiazolo/1,3,4-thiadiazolo)-pyrimidine derivatives.

    PubMed

    Shetty, Poornima; Praveen, B M; Raghavendra, M; Manjunath, K; Cheruku, Srinivas

    2016-05-01

    A series of novel 4-amino-6-(1,3,4-oxadiazolo/1,3,4-thiadiazolo)-pyrimidine derivatives of biological interest were prepared by sequential amination, hydrazide formation, and hydrazine carbothioamidination followed by cyclization. All the synthesized compounds (6a-6h and 7a-7f) were screened for antibacterial and antifungal activity. From this group, compound 7f (MIC (μg/mL μg/mL )/Inhibition (mm): 6.25/23-30) showed good antibacterial and antifungal activity. Reagents and conditions: (a) Ethyl acetoacetate, 60% NaH, 1,4-dioxane, 60°C, 6 h; (b) DIPEA, 1,4-dioxane, 100°C, 14 h; (c) NH2NH2 ⋅ H2O, EtOH, reflux, 14 h; (d) Tolyl isothiocyanatobenzene, DMF, RT, 2 h; (e) (if X = O) EDC⋅ HCl, TEA, DMF, RT, 14 h; (f) (if X = S) Conc. H2O4, RT, 14h. PMID:26498121

  8. Electron donor-acceptor interaction of 3,4-dimethylaniline with 2,3-dicyano-1,4-naphthoquinone

    NASA Astrophysics Data System (ADS)

    Neelgund, Gururaj M.; Magadum, Subash R.; Budni, M. L.

    2011-01-01

    The electron donor-acceptor (EDA) interaction between 2,3-dicyano-1,4-naphthoquinone (DCNQ) and 3,4-dimethylaniline (3,4-DMA) is studied in chloroform, dichloromethane and 1:1 (v/v) mixture of chloroform and dichloromethane. The rate of formation of the product was measured as a function of time using UV-vis spectrophotometer. The formation constant ( K) and molar extinction coefficient ( ɛ) values for the formation of EDA complex were evaluated in the temperature range of 20-35 °C. The pseudo-first-order rate constant ( k1) and the second-order rate constant ( k2) for the disappearance of EDA complex and for the formation of product were evaluated. The activation parameters (Δ H#, Δ S# and Δ G#) of the reaction were determined by temperature dependence of rate constants using the Arrhenius plots. The effect of relative permittivity of the medium on the reaction is discussed. The observed results indicate that formation of final product proceeds through initial formation of EDA complex as an intermediate. The product of the reaction was purified by column chromatography method and identified as 3-( N-3,4-dimethyl-phenylamino)-2-cyano-1,4-naphthoquinone by elemental analysis, IR and NMR spectroscopy. On the basis of kinetic, analytical and spectroscopic results, a plausible mechanism for the formation of EDA complex and its transformation into product is proposed.

  9. Structure determination of (Fe3O4)n+(n = 13) clusters via DFT

    NASA Astrophysics Data System (ADS)

    Li, Yanhua; Cai, Congzhong; Zhao, Chengjun; Gu, Yonghong

    2016-07-01

    In virtue of the particle swarm optimization (PSO) algorithm, the global minimum candidate structures with the lowest energy for (Fe3O4)n(n = 13) clusters were obtained by first-principles structural searches. The geometric structures and spin configurations of three cationic (Fe3O4)n+(n = 13) clusters have been identified for the first time by comparing the experimental IR spectra with the calculated results from density functional theory by using different exchange-correlation functionals. It is found that the lowest energy structures of these clusters are of a shape of hat, boat and tower, respectively, with a ferrimagnetic arrangement of spins, and M06L functional is more suitable for Fe3O4 clusters than other ones.

  10. 1,1',4,5-tetrahydrotrispiro[1,3,2-diazaphosphole-2,2'-[1,3,5,2,4,6]triazatriphosphinine-4',6''-dibenzo[d,f][1,3,2]dioxaphosphepine-6',6'''-dibenzo[d,f][1,3,2]dioxaphosphepine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The title compound 1,1',4,5-tetrahydrotrispiro[1,3,2-diazaphosphole-2,2'-[1,3,5,2,4,6]triazatriphosphinine-4',6''-dibenzo[d,f][1,3,2]dioxaphosphepine-6',6'''-dibenzo[d,f][1,3,2]dioxaphosphepine], C26H22N5O4P3, at 100°K has monoclinic (P21/c) symmetry and is achieved in a two step synthesis that does...

  11. Metabolism of a glucuronide conjugate of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats.

    PubMed

    Atawodi, S E; Michelsen, K; Richter, E

    1994-01-01

    Besides 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), [4-(methylnitrosamino)-1-(3-pyridyl)butl-yl]-beta-O-d-glucosidu ronic acid (NNAL-Glu) is another important metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) which has been detected in the urine of tobacco users and non-smokers heavily exposed to sidestream cigarette smoke. In order to evaluate the toxicological significance of NNAL-Glu formation and excretion, the metabolism of [5-3H]-NNAL-Glu was studied in rats. Five male F344 rats were administered 3.7 mg/kg [5-3H]-NNAL-Glu by i.v. injection and the metabolites in urine analysed by HPLC. More than 90% of the radioactivity was excreted in urine within the first 24 h. Unchanged NNAL-Glu accounted for 81.2 +/- 3.1% of the total radioactivity; the remaining part of the dose appears to be deconjugated resulting in the urinary excretion of NNAL (3.6 +/- 1.7%) and its alpha-hydroxylation (11.5 +/- 2.2%) and N-oxidation (3.6 +/- 1.6%) products. The presence of alpha-hydroxylation products of NNAL-Glu in urine suggests that this NNK metabolite may be activated in vivo to carcinogenic intermediates. PMID:7717849

  12. A convergent multipole expansion for 1,3 and 1,4 Coulomb interactions

    NASA Astrophysics Data System (ADS)

    Rafat, M.; Popelier, P. L. A.

    2006-04-01

    Traditionally force fields express 1,3 and 1,4 interactions as bonded terms via potentials that involve valence and torsion angles, respectively. These interactions are not modeled by point charge terms, which are confined to electrostatic interactions between more distant atoms (1,n where n >4). Here we show that both 1,3 and 1,4 interactions can be described on the same footing as 1,n (n>4) interactions by a convergent multipole expansion of the Coulomb energy of the participating atom pairs. The atomic multipole moments are generated by the theory of quantum chemical topology. The procedure to make the multipole expansion convergent is based on a "shift procedure" described in earlier work [L. Joubert and P. L. A. Popelier, Molec. Phys. 100, 3357 (2002)].

  13. Discovery of N-(4-(2-Amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a Selective and Orally Efficacious Inhibitor of the Met Kinase Superfamily

    SciTech Connect

    Schroeder, Gretchen M.; An, Yongmi; Cai, Zhen-Wei; Chen, Xiao-Tao; Clark, Cheryl; Cornelius, Lyndon A.M.; Dai, Jun; Gullo-Brown, Johnni; Gupta, Ashok; Henley, Benjamin; Hunt, John T.; Jeyaseelan, Robert; Kamath, Amrita; Kim, Kyoung; Lippy, Jonathan; Lombardo, Louis J.; Manne, Veeraswamy; Oppenheimer, Simone; Sack, John S.; Schmidt, Robert J.; Shen, Guoxiang; Stefanski, Kevin; Tokarski, John S.; Trainor, George L.; Wautlet, Barri S.; Wei, Donna; Williams, David K.; Zhang, Yingru; Zhang, Yueping; Fargnoli, Joseph; Borzilleri, Robert M.

    2009-12-01

    Substituted N-(4-(2-aminopyridin-4-yloxy)-3-fluoro-phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamides were identified as potent and selective Met kinase inhibitors. Substitution of the pyridine 3-position gave improved enzyme potency, while substitution of the pyridone 4-position led to improved aqueous solubility and kinase selectivity. Analogue 10 demonstrated complete tumor stasis in a Met-dependent GTL-16 human gastric carcinoma xenograft model following oral administration. Because of its excellent in vivo efficacy and favorable pharmacokinetic and preclinical safety profiles, 10 has been advanced into phase I clinical trials.

  14. Synthesis, mesomorphic properties and X-ray diffraction studies on 7-alkyloxy-3-(4-alkyloxyphenyl-4H-1-benzopyran-4-one: Crystal structure of 7-hexyloxy-3-(4-hexyloxyphenyl)-4H-1-benzopyran-4-one

    NASA Astrophysics Data System (ADS)

    Yeap, Guan-Yeow; Yam, Wan-Sinn; Dobrzyscky, Lucasz; Gorecka, Ewa; Takeuchi, Daisuke; Boey, Peng-Lim; Mahmood, Wan Ahmad Kamil; Ito, Masato M.

    2009-11-01

    Eight new compounds, 7-alkyloxy-3-(4-alkyloxyphenyl)-4H-1-benzopyran-4-one incorporating isoflavone core and identical terminal side chains, OR (where R = C nH 2n+1 with n ranging from 4 to 18 in even parity) have been synthesized and isolated. The thermal stability in relation to the phase behaviour and respective enthalpy values of these compounds were analyzed using differential scanning calorimetry. The texture of the preferred molecular orientation at different temperatures was observed under polarized light wherein all compounds exhibited nematic (N), smectic A (SmA) and smectic C (SmC) phases. The difference in mesogenicity of these compounds was also investigated from the viewpoints of conformation and polarity of the side chains which contributed remarkably towards the change in the intermolecular interaction within the mesophase. X-ray diffraction technique was employed to investigate the molecular packing associated with the intermolecular interaction as well as the correlation between the thermal behaviour of these compounds with their anisotropy properties within a mesophase. The molecular structure of compound 7-hexyloxy-3-(4-hexyloxyphenyl)-4H-1-benzopyran-4-one in crystal phase was confirmed by single-crystal X-ray diffraction.

  15. Syntheses and Degradations of Fluorinated Heterocyclics. 3; Perfluoroalkyl and Perfluoroalkylether-1,3,4-Oxadiazoles

    NASA Technical Reports Server (NTRS)

    Paciorek, K. J. L.; Kaufman, J.; Nakahara, J. H.; Ito, T. I.; Kratzer, R. H.; Rosser, R. W.; Parker, J. A.

    1977-01-01

    2,5-Bis(perfluoro-n-heptyl)-, 2-perfluoroalkylether-5-perfluoro-n- heptyl- , and 2 , 5-bisperfluoroalkylether-1,3,4-oxadiazoles were synthesized and characterized. 2,5-Bis(perfluoro-n-heptyl)-1,3,4-oxadiazole was thermally and hydrolytically stable at 325 C; however, in the presence of air, degradation took place at 235 C. The perfluoroalkylether analogue exhibited thermal and hydrolytic stability at 325 C; it was found to be unaffected by jet-A fuel and air at 235 C. At 325 C in air some degradation occurred as evidenced by volatiles production, oxygen consumption, and 96% starting material recovery.

  16. 3-Benzyl-7-(2,4-dichloro-phen-yl)-4H-1,3,4-thia-diazolo[2,3-c][1,2,4]triazin-4-one.

    PubMed

    Fun, Hoong-Kun; Arshad, Suhana; Sarojini, B K; Imran, U A; Krishna, B G

    2012-06-01

    In the title compound, C(17)H(10)Cl(2)N(4)OS, the phenyl ring and the H atoms attached to the adjacent C atom are disordered over two positions, with refined site occupancies of 0.509 (8) and 0.491 (8). The planar 4H-1,3,4-thia-diazolo[2,3-c][1,2,4]triazine ring system [maximum deviation = 0.048 (3) Å] forms dihedral angles of 76.9 (5), 74.9 (5) and 9.88 (12)°, respectively, with the major and minor parts of the disordered phenyl ring and with the dichloro-substituted benzene ring. In the crystal, pairs of C-H⋯O hydrogen bonds link the mol-ecules, forming inversion dimers with an R(2) (2)(18) graph-set motif. A short S⋯N contact of 2.801 (3) Å is observed between the dimers. PMID:22719523

  17. 4-(5-Phenyl-1,2,4-triazolo[3,4-a]isoquinolin-3-yl)benzonitrile

    PubMed Central

    Khan, F. Nawaz; Manivel, P.; Prabakaran, K.; Hathwar, Venkatesha R.; Akkurt, Mehmet

    2010-01-01

    In the title mol­ecule, C23H14N4, the triazoloisoquinoline ring system is nearly planar, with an r.m.s. deviation of 0.038 (2) Å and a maximum deviation of −0.030 (2) Å from the mean plane of the triazole ring C atom which is bonded to the benzene ring. The benzene and phenyl rings are twisted by 57.65 (8) and 53.60 (9)°, respectively, with respect to the mean plane of the triazoloisoquinoline ring system. In the crystal structure, mol­ecules are linked by weak aromatic π–π inter­actions [centroid–centroid distance = 3.8074 (12) Å]. In addition, the crystal structure exhibits a nonclassical inter­molecular C—H⋯N hydrogen bond. PMID:21579135

  18. Structure activity optimization of 6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazines as Jak1 kinase inhibitors.

    PubMed

    Friedman, Michael; Frank, Kristine E; Aguirre, Ana; Argiriadi, Maria A; Davis, Heather; Edmunds, Jeremy J; George, Dawn M; George, Jonathan S; Goedken, Eric; Fiamengo, Bryan; Hyland, Deborah; Li, Bin; Murtaza, Anwar; Morytko, Michael; Somal, Gagandeep; Stewart, Kent; Tarcsa, Edit; Van Epps, Stacy; Voss, Jeffrey; Wang, Lu; Woller, Kevin; Wishart, Neil

    2015-10-15

    Previous work investigating tricyclic pyrrolopyrazines as kinase cores led to the discovery that 1-cyclohexyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (12) had Jak inhibitory activity. Herein we describe our initial efforts to develop orally bioavailable analogs of 12 with improved selectivity of Jak1 over Jak2. PMID:26372653

  19. 4,4'-Dichlorodiphenyltrichloroethane (DDT) and 4,4'-dichlorodiphenyldichloroethylene (DDE) promote adipogenesis in 3T3-L1 adipocyte cell culture.

    PubMed

    Kim, Jonggun; Sun, Quancai; Yue, Yiren; Yoon, Kyong Sup; Whang, Kwang-Youn; Marshall Clark, J; Park, Yeonhwa

    2016-07-01

    4,4'-Dichlorodiphenyltrichloroethane (DDT), a chlorinated hydrocarbon insecticide, was extensively used in the 1940s and 1950s. DDT is mainly metabolically converted into 4,4'-dichlorodiphenyldichloroethylene (DDE). Even though most countries banned DDT in the 1970s, due to the highly lipophilic nature and very stable characteristics, DDT and its metabolites are present ubiquitously in the environment, including food. Recently, there are publications on relationships between exposure to insecticides, including DDT and DDE, and weight gain and altered glucose homeostasis. However, there are limited reports regarding DDT or DDE and adipogenesis, thus we investigated effects of DDT and DDE on adipogenesis using 3T3-L1 adipocytes. Treatment of DDT or DDE resulted in increased lipid accumulation accompanied by increased expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome-proliferator activated receptor-γ (PPARγ), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), adipose triglyceride lipase, and leptin. Moreover, treatment of DDT or DDE increased protein levels of C/EBPα, PPARγ, AMP-activated protein kinase-α (AMPKα), and ACC, while significant decrease of phosphorylated forms of AMPKα and ACC were observed. These finding suggest that increased lipid accumulation caused by DDT and DDE may mediate AMPKα pathway in 3T3-L1 adipocytes. PMID:27265825

  20. Basal and 3,3',4,4',5-pentachlorobiphenyl-induced expression of cytochrome P450 1A, 1B and 1C genes in zebrafish

    SciTech Connect

    Joensson, Maria E. . E-mail: mjonsson@whoi.edu; Orrego, Rodrigo; Woodin, Bruce R.; Goldstone, Jared V.; Stegeman, John J.

    2007-05-15

    The cytochrome P4501C (CYP1C) gene subfamily was recently discovered in fish, and zebrafish (Danio rerio) CYP1C1 transcript has been cloned. Here we cloned the paralogous CYP1C2, showing that the amino acid sequence is 78% identical to CYP1C1, and examined gene structure and expression of CYP1A, CYP1B1, CYP1C1, and CYP1C2. Xenobiotic response elements were observed upstream of the coding regions in all four genes. Zebrafish adults and embryos were exposed (24 h) to 100 nM 3,3',4,4',5-polychlorinated biphenyl (PCB126) or 20 ppm acetone and subsequently held in clean water for 24 h (adults) or 48 h (embryos). All adult organs examined (eye, gill, heart, liver, kidney, brain, gut, and gonads) and embryos showed basal expression of the four genes. CYP1A was most strongly expressed in liver, whereas CYP1B1, CYP1C1, and CYP1C2 were most strongly expressed in heart and eye. CYP1B1 and the CYP1C genes showed an expression pattern similar to one another and to mammalian CYP1B1. In embryos CYP1C1 and CYP1C2 tended to have a higher basal expression than CYP1A and CYP1B1. PCB126 induced CYP1A in all organs, and CYP1B1 and CYP1C1 in all organs except gonads, or gonads and brain, respectively. CYP1C2 induction was significant only in the liver. However, in embryos all four genes were induced strongly by PCB126. The results are consistent with CYP1C1 and CYP1C2, as well as CYP1A and CYP1B1, being regulated by the aryl hydrocarbon receptor. While CYP1A may have a protective role against AHR agonists in liver and gut, CYP1B1, CYP1C1, and CYP1C2 may also play endogenous roles in eye and heart and possibly other organs, as well as during development.

  1. A structural study of (1RS,2SR,3RS,4SR,5RS)-2,4-dibenzoyl-1,3,5-triphenylcyclohexan-1-ol chloroform hemisolvate and (1RS,2SR,3RS,4SR,5RS)-2,4-dibenzoyl-1-phenyl-3,5-bis(2-methoxyphenyl)cyclohexan-1-ol.

    PubMed

    Minyaev, Mikhail E; Roitershtein, Dmitrii M; Nifant'ev, Ilya E; Ananyev, Ivan V; Minyaeva, Tatyana V; Mikhaylyev, Timofey A

    2015-06-01

    (1RS,2SR,3RS,4SR,5RS)-2,4-Dibenzoyl-1,3,5-triphenylcyclohexan-1-ol or (4-hydroxy-2,4,6-triphenylcyclohexane-1,3-diyl)bis(phenylmethanone), C38H32O3, (1), is formed as a by-product in the NaOH-catalyzed synthesis of 1,3,5-triphenylpentane-1,5-dione from acetophenone and benzaldehyde. Single crystals of the chloroform hemisolvate, C38H32O3·0.5CHCl3, were grown from chloroform. The structure has triclinic (P1) symmetry. One diastereomer [as a pair of (1RS,2SR,3RS,4SR,5RS)-enantiomers] of (1) has been found in the crystal structure and confirmed by NMR studies. The dichoromethane hemisolvate has been reported previously [Zhang et al. (2007). Acta Cryst. E63, o4652]. (1RS,2SR,3RS,4SR,5RS)-2,4-Dibenzoyl-3,5-bis(2-methoxyphenyl)-1-phenylcyclohexan-1-ol or [4-hydroxy-2,6-bis(2-methoxyphenyl)-4-phenylcyclohexane-1,3-diyl]bis(phenylmethanone), C40H36O5, (2), is also formed as a by-product, under the same conditions, from acetophenone and 2-methoxybenzaldehyde. Crystals of (2) have been grown from chloroform. The structure has orthorhombic (Pca2₁) symmetry. A diastereomer of (2) possesses the same configuration as (1). In both structures, the cyclohexane ring adopts a chair conformation with all bulky groups (benzoyl, phenyl and 2-methoxyphenyl) in equatorial positions. The molecules of (1) and (2) both display one intramolecular O-H···O hydrogen bond. PMID:26044332

  2. Synthesis of 1,4-enamino ketones by [3,3]-rearrangements of dialkenylhydroxylamines.

    PubMed

    Pecak, Wiktoria H; Son, Jongwoo; Burnstine, Amy J; Anderson, Laura L

    2014-07-01

    The synthesis of 1,4-enamino ketones has been achieved through the [3,3]-rearrangement of dialkenylhydroxylamines generated from the addition of N-alkenylnitrones to electron-deficient allenes. The mild conditions required for this reaction, and the simultaneous installation of a fluorenyl imine N-protecting group as a consequence of the rearrangement, avoid spontaneous cyclization of the 1,4-enamino ketones to form the corresponding pyrroles and allow for the isolation and controlled divergent functionalization of these reactive intermediates. The optimization, scope, and tolerance of the new method are discussed with demonstrations of the utility of the products for the synthesis of pyrroles, 1,4-diones, and furans. PMID:24961680

  3. 4-Oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as New Axl Kinase Inhibitors.

    PubMed

    Tan, Li; Zhang, Zhang; Gao, Donglin; Luo, Jinfeng; Tu, Zheng-Chao; Li, Zhengqiu; Peng, Lijie; Ren, Xiaomei; Ding, Ke

    2016-07-28

    Axl is a new potential target for anticancer drug discovery. A series of 4-oxo-1,4-dihydroquinoline-3-carboxamides were designed and synthesized as highly potent Axl kinase inhibitors. One of the most promising compounds, 9im, tightly bound with Axl protein and potently inhibited its kinase function with a Kd value of 2.7 nM and an IC50 value of 4.0 nM, respectively, while was obviously less potent against most of the 403 wild-type kinases evaluated at a relatively high concentration. The compound dose-dependently inhibited the TGF-β1-induced epithelial-mesenchymal transition (EMT) and suppressed the migration and invasion of MDA-MB-231 breast cancer cells. In addition, 9im also demonstrated reasonable pharmacokinetics properties in rats and exhibited in vivo therapeutic effect on hepatic metastasis in a xenograft model of highly metastatic 4T1 murine breast cancer cells. Compound 9im may serve as a lead compound for new anticancer drug discovery and a valuable research probe for further biological investigation on Axl. PMID:27379978

  4. DNA Mismatch Repair Interacts with CAF-1- and ASF1A-H3-H4-dependent Histone (H3-H4)2 Tetramer Deposition.

    PubMed

    Rodriges Blanko, Elena; Kadyrova, Lyudmila Y; Kadyrov, Farid A

    2016-04-22

    DNA mismatch repair (MMR) is required for the maintenance of genome stability and protection of humans from several types of cancer. Human MMR occurs in the chromatin environment, but little is known about the interactions between MMR and the chromatin environment. Previous research has suggested that MMR coincides with replication-coupled assembly of the newly synthesized DNA into nucleosomes. The first step in replication-coupled nucleosome assembly is CAF-1-dependent histone (H3-H4)2 tetramer deposition, a process that involves ASF1A-H3-H4 complex. In this work we used reconstituted human systems to investigate interactions between MMR and CAF-1- and ASF1A-H3-H4-dependent histone (H3-H4)2 tetramer deposition. We have found that MutSα inhibits CAF-1- and ASF1A-H3-H4-dependent packaging of a DNA mismatch into a tetrasome. This finding supports the idea that MMR occurs before the DNA mismatch is packaged into the tetrasome. Our experiments have also revealed that CAF-1- and ASF1A-H3-H4-dependent deposition of the histone (H3-H4)2 tetramers does not interfere with MMR reactions. In addition, we have established that unnecessary degradation of the discontinuous strand that takes place in both DNA polymerase δ (Pol δ)- and DNA polymerase ϵ (Pol ϵ)-dependent MMR reactions is suppressed by CAF-1- and ASF1A-H3-H4-dependent deposition of the histone (H3-H4)2 tetramers. These data suggest that CAF-1- and ASF1A-H3-H4-dependent deposition of the histone (H3-H4)2 tetramers is compatible with MMR and protects the discontinuous daughter strand from unnecessary degradation by MMR machinery. PMID:26945061

  5. Agonist induced formation of myoinositol 1,4,5-P/sub 3/, myoinositol 1,3,4-P/sub 3/ and myoinositol-P/sub 4/ in rat liver parenchymal cells

    SciTech Connect

    Blackmore, P.F.; Bocckino, S.; Jiang, H.; Exton, J.H.

    1986-05-01

    Treatment of hepatocytes with vasopressin (10/sup -7/ M) resulted in a rapid and large (approximately 7-fold) increase in myoinositol 1,4,5-P/sub 3/ (I 1,4,5-P/sub 3/) at 10 s which slowly declined over the next 30 s to reach a steady level (approximately 2-fold increase). IP/sub 4/ also increased (approximately 4-fold) at 10 s. The level of I 1,3,4-P/sub 3/ also increased approximately 100% at 2 min after a lag of approximately 20 s. The increase in I 1,4,5-P/sub 3/ correlates temporally with the increase in cytosolic free Ca/sup 2 +/. The dose response curves of vasopressin to increase I 1,4,5-P/sub 3/, I 1,3,4-P/sub 3/ and IP/sub 4/ measured at 1 min were similar. Other Ca/sup 2 +/ mobilizing agonists (ATP, angiotensin II, epinephrine, AlF/sub 4//sup -/ and glucagon) also increased I 1,4,5-P/sub 3/, I 1,3,4-P/sub 3/ and IP/sub 4/ to varying degrees. Incubation of permeabilized hepatocytes with (2-/sup 3/H)I 1,4,5-P/sub 3/ in the presence of MgATP resulted in the formation of (/sup 3/H)IP/sub 4/ and (/sup 3/H)I 1,3,4-P/sub 3/. Also I 1,4,5-P/sub 3/ was converted to (/sup 32/P)IP/sub 4/ in the presence of (..gamma..-/sup 32/P)ATP. Phosphorylation of I 1,4,5-P/sub 3/ to I 1,3,4,5-P/sub 4/, followed by dephosphorylation could result in the formation of I 1,3,4-P/sub 3/ and would account for the formation of these compounds following hormone stimulation of hepatocytes.

  6. Material Property Correlations: Comparisons between FRAPCON-3.4, FRAPTRAN 1.4, and MATPRO

    SciTech Connect

    Luscher, Walter G.; Geelhood, Kenneth J.

    2010-08-01

    . In addition to describing the material property correlations used in the subroutines of FRAPCON-3 and FRAPTRAN, this report also provides a variety of comparisons between material property correlations and data. Although they are frequently identical, comparisons are made between the material property correlations used in the FRAPCON-3 and FRAPTRAN codes. Comparisons are also made between the material property correlations used in MATPRO, a compilation of fuel and cladding material property correlations with an extensive history of used with various fuel performance and severe accident codes. For a number of reasons, consistency between the material property correlations in FRAPCON-3, FRAPTRAN, and MATPRO has never been complete. However, the current versions of FRAPCON-3 and FRAPTRAN use a relatively consistent set of correlations for the properties that are used by both codes. The material property correlations in the most recent version of MATPRO are documented in Volume 4 of NUREG/CR-6150. In addition to comparison of the various correlations, correlation-to-data comparisons are also made with FRAPCON-3, FRAPTRAN, and MATPRO. All comparisons made in this report are based on the material property correlations used in the most recent version of the FRAPCON-3 and FRAPTRAN codes, FRAPCON-3.4 and FRAPTRAN 1.4. The source code for each material property correlation discussed will be provided for FRAPCON-3.4 and FRAPTRAN 1.4 (see appendix) as well as a range of applicability and an estimate of uncertainty where possible.

  7. Scaling, cumulant ratios, and height distribution of ballistic deposition in 3 +1 and 4 +1 dimensions

    NASA Astrophysics Data System (ADS)

    Alves, Sidiney G.; Ferreira, Silvio C.

    2016-05-01

    We investigate the origin of the scaling corrections in ballistic deposition models in high dimensions using the method proposed by Alves et al. [Phys. Rev. E 90, 052405 (2014), 10.1103/PhysRevE.90.052405] in d =2 +1 dimensions, where the intrinsic width associated with the fluctuations of the height increments during the deposition processes is explicitly taken into account. In the present work, we show that this concept holds for d =3 +1 and 4 +1 dimensions. We have found that growth and roughness exponents and dimensionless cumulant ratios are in agreement with other models, presenting small finite-time corrections to the scaling, that in principle belong to the Kardar-Parisi-Zhang (KPZ) universality class in both d =3 +1 and 4 +1 . Our results constitute further evidence that the upper critical dimension of the KPZ class, if it exists, is larger than 4.

  8. 10 CFR 960.3-1-4 - Evidence for siting decisions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Evidence for siting decisions. 960.3-1-4 Section 960.3-1-4 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4 Evidence for siting decisions. The...

  9. 10 CFR 960.3-1-4 - Evidence for siting decisions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Evidence for siting decisions. 960.3-1-4 Section 960.3-1-4 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4 Evidence for siting decisions. The...

  10. 10 CFR 960.3-1-4 - Evidence for siting decisions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Evidence for siting decisions. 960.3-1-4 Section 960.3-1-4 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4 Evidence for siting decisions. The...

  11. 10 CFR 960.3-1-4 - Evidence for siting decisions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Evidence for siting decisions. 960.3-1-4 Section 960.3-1-4 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4 Evidence for siting decisions. The...

  12. 10 CFR 960.3-1-4 - Evidence for siting decisions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Evidence for siting decisions. 960.3-1-4 Section 960.3-1-4 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4 Evidence for siting decisions. The...

  13. 40 CFR 721.10077 - 3H-1,2,4-Triazol-3-one, 1,2-dihydro-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 3H-1,2,4-Triazol-3-one, 1,2-dihydro-. 721.10077 Section 721.10077 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10077...

  14. Chemistry of the pyrazolidines. 26. Alkylation of 4-benzyliden-1-phenyl-3,5-dioxopyrazolidines

    SciTech Connect

    Moldarev, B.L.; Aronzon, M.E.; Adanin, V.M.; Zyakun, A.M.

    1986-08-01

    The reaction of 4-benzyliden-1-phenyl-3,5-dioxopyrazolidines with alkyl halides in the presence of sodium alkoxide gave 1-phenyl-2-alkyl-4-benzyliden- and 1-phenyl-2,4-dialkyl-4-(..cap alpha..-alkoxybenzyl)-3,4-dioxopyrazolines. The structures of these compounds were confirmed by UV, IR, and PMR spectroscopy, and by mass-spectrometry.

  15. Synthesis and stereochemistry of 1,3,2-oxazaphosphorino[4,3- a]isoquinolines

    NASA Astrophysics Data System (ADS)

    Fülöp, F.; Forró, E.; Martinek, T.; Günther, G.; Sillanpää, R.

    2000-11-01

    1,3,2-Oxazaphosphorino[4,3- a]isoquinolines 8a,b, 9a,b and 10a were synthesized by the reactions of homocalycotomine 7 with appropriate dichlorophosphorus derivatives, such as phenylphosphonic dichloride, bis(2-chloroethyl)phosphonic dichloride or phosphoryl chloride. In spite of the blocking effect of the connecting isoquinoline ring system, the oxazaphosphorinane moiety exists as a chair-twist equilibrium, where the conformer ratios are strongly dependent on the P-4 configuration and the stereoelectronic properties of the substituents.

  16. Amperometric carbon paste enzyme electrodes with Fe(3)O(4) nanoparticles and 1,4-benzoquinone for glucose determination.

    PubMed

    Erden, Pınar Esra; Zeybek, Bülent; Pekyardımcı, Şule; Kılıç, Esma

    2013-06-01

    Two new amperometric carbon paste enzyme electrodes including Fe(3)O(4) nanoparticles with and without 1,4-benzoquinone were developed for glucose determination. Electron transfer properties of unmodified and Fe(3)O(4) nanoparticles and/or 1,4-benzoquinone modified carbon paste electrodes were investigated in 0.1 M KCl support electrolyte containing Fe(CN)6(3-/4-) as redox probe by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods. Fe(3)O(4) nanoparticles increased electron transfer at solution/electrode interface. The parameters affecting the analytical performance of the enzyme electrode have been investigated in detail and optimized for Fe(3)O(4) nanoparticle modified enzyme electrode (Fe(3)O(4)-CPEE). Fe(3)O(4) nanoparticles and 1,4-benzoquinone modified enzyme electrode (BQ-Fe(3)O(4)-CPEE) exhibited linear response from 1.9 × 10(-7) M to 3.7 × 10(-6) M, from 7.2 × 10(-6) M to 1.5 × 10(-4) M and from 1.3 × 10(-3) M to 1.2 × 10(-2) M with an excellent detection limit of 1.9 × 10(-8) M. BQ-Fe(3)O(4)-CPEE was used for determination of glucose in serum samples and results were in good agreement with those obtained by spectrophotometric method. PMID:22889252

  17. Inositol 1,3,4,6-tetrakisphosphate mobilizes calcium in Xenopus oocytes with high potency.

    PubMed Central

    Ivorra, I; Gigg, R; Irvine, R F; Parker, I

    1991-01-01

    Injection of Ins(1,3,4,6)P4 into Xenopus oocytes evoked Ca2(+)-dependent membrane currents with a potency 5-10 times less than Ins(1,4,5)P3, whereas Ins(1,3,4)P3 and Ins(1,3,4,5,6)P5 were almost ineffective. Responses to Ins(1,3,4,6)P4 arose through liberation of intracellular Ca2+ and through entry of extracellular Ca2+. These results, together with the observation that Ins(1,3,4,6)P4 facilitated responses to Ins(1,4,5)P3, suggests that both of these compounds may act on the same intracellular receptors. PMID:1991032

  18. Tin(IV) tetrahalide complexes of 2-amino-1,3,4-thiadiazole and 2-ethylamino-1,3,4-thiadiazole

    NASA Astrophysics Data System (ADS)

    Benedetti, Adriano; Fabretti, Antonio C.; Peyronel, Giorgio; Zanoli, Aline F.

    The following tin(IV) tetrahalide complexes of 2-amino-1,3,4-thiadiazole ( atz, L) and 2-ethylamino-1,3,4-thiadiazole ( eatz, L') have been prepared and investigated by i.r. and Raman spectroscopy: SnCl 4L 1.5, SnBr 4L 1.5, SnBr 4L 4, SnI 4L 3, SnI 4L 6, SnCl 4L' 1.33, SnCl 4L' 2.25·CH 2Cl 2, SnBr 4L' 2, SnBr 4L' 3, SnBr 4L' 5, SnI 4L' 5. The ligands are bonded through the aminic nitrogen atom with ν(SnN) bands in the 555-385 and 520-355 cm -1 regions for the atz and eatz complexes, respectively. In some complexes some bridging ligand molecules may be bonded also through a ring-nitrogen atom. For the first four eatz-complexes a cis-configuration may be established.

  19. Synthesis and antiproliferative activity of imidazo[2,1-b][1,3,4]thiadiazole derivatives.

    PubMed

    Kumar, Sujeet; Gopalakrishnan, Vidya; Hegde, Mahesh; Rana, Vivek; Dhepe, Sharad S; Ramareddy, Sureshbabu A; Leoni, Alberto; Locatelli, Alessandra; Morigi, Rita; Rambaldi, Mirella; Srivastava, Mrinal; Raghavan, Sathees C; Karki, Subhas S

    2014-10-01

    A series of 2,5,6-substituted imidazo[2,1-b][1,3,4]thiadiazole derivatives have been prepared and were tested for antiproliferative activity on cancer cells at the National Cancer Institute. Results showed that molecules with a benzyl group at position 2, exhibited an increase in activity for the introduction of a formyl group at the 5 position. The compound 2-benzyl-5-formyl-6-(4-bromophenyl)imidazo[2,1-b][1,3,4]thiadiazole 22 has been chosen for understanding the mechanism of action by various molecular and cellular biology studies. Results obtained from cell cycle evaluation analysis, analysis of mitochondrial membrane potential and Annexin V-FITC by flow cytometric analysis, ROS production and expression of apoptotic and DNA-repair proteins suggested that compound 22 induced cytotoxicity by activating extrinsic pathway of apoptosis, however, without affecting cell cycle progression. PMID:25205189

  20. 1,4-Dibromo-butane-2,3-dione.

    PubMed

    Zai, De-Xin

    2012-11-01

    The asymmetric unit of the title compound, C(4)H(4)Br(2)O(2), contains one half-mol-ecule, being located about a centre of inversion. In the crystal, there are no significant inter-molecular inter-actions. PMID:23284543

  1. Synthesis and antiestrogenic activity of [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl][4-[2-(1-pyrrolidinyl)ethoxy]-phenyl]methanone, methanesulfonic acid salt.

    PubMed

    Jones, C D; Suarez, T; Massey, E H; Black, L J; Tinsley, F C

    1979-08-01

    Acylation of the sodio anion of beta-tetralone with phenyl anisoate, followed by a Grignard reaction of the resultant 4 with 4-methoxyphenylmagnesium bromide, gave rise to two novel dihydronaphthalene isomers 5 and 6. Regioselective demethylation of either 5 or 6 by NaSEt produced [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl](4-hydroxyphenyl)methanone (7). Etherification of the phenolic group of 7 by N-(2-chloroethyl)pyrrolidine and subsequent methanesulfonate salt formation provided [3,4-dihydro-2-(4-methoxyphenyl)-1-maphthalenyl

  2. Greener and rapid access to bio-active heterocycles: one-pot solvent-free synthesis of 1,3,4-oxadiazoles and 1,3,4-thiadiazoles

    EPA Science Inventory

    A novel one-pot solvent free synthesis of 1,3,4-oxadiazoles and 1,3,4-thiadiazoles by condensation of acid hydrazide and triethyl orthoalkanates under microwave irradiations is reported. This green protocol was catalyzed efficiently by solid supported Nafion®NR50 and phosphorus p...

  3. An efficient, overall [4+1] cycloaddition of 1,3-dienes and nitrene precursors.

    PubMed

    Wu, Qiong; Hu, Jian; Ren, Xinfeng; Zhou, Jianrong

    2011-10-01

    Intermolecular cycloadditions of conjugated dienes and nitrene precursors usually produce aziridines. A generally useful method was lacking to directly provide the [4+1] cycloadducts, 3-pyrrolines. We have realized this transformation by using an uniquely active catalyst, copper(II) 1,1,1,5,5,5-hexafluoroacetylacetonate ([Cu(hfacac)(2)]). The method is applicable to a wide array of dienes with good yields. When 1,4-disubstituted dienes are used as substrates, good-to-excellent cis or trans selectivity can be obtained. Interestingly, the cis or trans preference depends on the nature of the substituents, rather than diene geometry. Mechanistic studies reveal that the [4+1] cycloaddition proceeds through diene aziridination and subsequent ring expansion. Among common copper catalysts, only [Cu(hfacac)(2)] can efficiently catalyze both steps, which explains the unique efficiency of the catalyst. PMID:21887836

  4. Conformational analysis of a nucleoside of 1,4-dihydro-4-oxoquinoline-3-carboxylic acid analogue

    NASA Astrophysics Data System (ADS)

    Zaccur Leal, Kátia; Rudolf Seidl, Peter; Diniz Yoneda, Julliane; Santos, CarlaV. B.; Marques, Isakelly P.; Souza, Maria Cecília B. V.; Francisco Ferreira, Vitor

    2005-06-01

    The synthesis of new ribonucleosides is an essential research area in the investigation of new therapeutically useful agents, particularly those used in the treatment of HIV infection. The conformation of these nucleosides may have direct implications for their ability to bind to receptor targets. We have prepared the 7-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid derivatives and used the ensemble of low-energy minima to develop conformational profiles of quinolonic nucleosides and verify their accuracy in different calculations of structural parameters. Results are compared with experimental data obtained by X-ray and NMR analysis. Finally, we intend to test the applicability of these methods to conformational analysis of other nucleosides and verify if the preferential conformation is the one which gives the best anti-HIV or antiviral activity.

  5. Crystal structure of 1-mesityl-3-methyl-4-phenyl-1H-1,2,3-triazol-3-ium iodide

    PubMed Central

    Canseco-González, Daniel; García, Juventino J.; Flores-Alamo, Marcos

    2015-01-01

    In the cation of the title salt, C18H20N3 +·I−, the mesityl and phenyl rings are inclined to the central triazolium ring by 61.39 (16) and 30.99 (16)°, respectively, and to one another by 37.75 (15)°. In the crystal, mol­ecules are linked via C—H⋯I hydrogen bonds, forming slabs parallel to the ab plane. Within the slabs there are weak π–π inter­actions present involving the mesityl and phenyl rings [inter-centroid distances are 3.8663 (18) and 3.8141 (18) Å]. PMID:26870488

  6. Crystal structure of 1-mesityl-3-methyl-4-phenyl-1H-1,2,3-triazol-3-ium iodide.

    PubMed

    Canseco-González, Daniel; García, Juventino J; Flores-Alamo, Marcos

    2015-12-01

    In the cation of the title salt, C18H20N3 (+)·I(-), the mesityl and phenyl rings are inclined to the central triazolium ring by 61.39 (16) and 30.99 (16)°, respectively, and to one another by 37.75 (15)°. In the crystal, mol-ecules are linked via C-H⋯I hydrogen bonds, forming slabs parallel to the ab plane. Within the slabs there are weak π-π inter-actions present involving the mesityl and phenyl rings [inter-centroid distances are 3.8663 (18) and 3.8141 (18) Å]. PMID:26870488

  7. Fe3O4(110)-(1 × 3) revisited: Periodic (111) nanofacets

    NASA Astrophysics Data System (ADS)

    Parkinson, Gareth S.; Lackner, Peter; Gamba, Oscar; Maaß, Sebastian; Gerhold, Stefan; Riva, Michele; Bliem, Roland; Diebold, Ulrike; Schmid, Michael

    2016-07-01

    The structure of the Fe3O4(110)-(1 × 3) surface was studied with scanning tunneling microscopy (STM), low-energy electron diffraction (LEED), and reflection high-energy electron diffraction (RHEED). The so-called one-dimensional reconstruction is characterized by bright rows that extend hundreds of nanometers in the [ 1 bar10] direction and have a periodicity of 2.52 nm in [001] in STM. It is concluded that this reconstruction is the result of a periodic faceting to expose {111}-type planes with a lower surface energy.

  8. Anticonvulsant activity of a mGlu(4alpha) receptor selective agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid.

    PubMed

    Chapman, A G; Talebi, A; Yip, P K; Meldrum, B S

    2001-07-20

    The metabotropic Group III agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid (ACPT-1), selective for the mGlu(4alpha) receptor, suppresses sound-induced seizures in DBA/2 mice following its intracerebroventricular (i.c.v.) administration (ED(50) 5.6 [2.9-10.7], nmol i.c.v., 15 min, clonic phase) and in genetically epilepsy-prone (GEP) rats following focal administration into the inferior colliculus (ED(50) 0.08 [0.01-0.50], nmol, 60 min, clonic phase). ACPT-1 also protects against clonic seizures induced in DBA/2 mice by the Group I agonist, (RS)-3,5-dihydroxyphenylglycine (3,5-DHPG) (ED(50) 0.60 [0.29-1.2], nmol i.c.v.) and by the Group III antagonist, (RS)-alpha-methylserine-O-phosphate (MSOP) (ED(50) 49.3 [37.9-64.1], nmol i.c.v.). Another Group III agonist, (RS)-4-phosphonophenyl-glycine (PPG), preferentially activating the mGlu(8) receptor, previously shown to protect against sound-induced seizures in DBA/2 mice and GEP rats, also protects against seizures induced in DBA/2 by 3,5-DHPG (ED(50) 3.7 [2.4-5.7], nmol i.c.v.) and by the Group III antagonist, MSOP (ED(50) 40.2 [21.0-77.0], nmol i.c.v.). At very high doses (500 nmol i.c.v. and above), Group III antagonists have pro-convulsant and convulsant activity. The anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(4) receptor agonist ACPT-1, is partially reversed by the co-administration of the Group III antagonists, MSOP, (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) or (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4), in the 20-50 nmol dose range. At doses of 50-200 nmol, MPPG and MAP4 cause further reversal of the ACPT-1 anticonvulsant protection, while the MSOP effect on ACPT-1 protection is abolished at higher doses. In contrast, the anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(8) receptor agonist PPG, is not

  9. STS-1 operational flight profile. Volume 4: Onorbit profile-cycle 3.1.1

    NASA Technical Reports Server (NTRS)

    1980-01-01

    The orbital flight test (OFT) phase of the shuttle program consists of four orbital flights beginning in November 1980and continuing through 1981. The major purpose of the OFT program is to demonstrate and verify shuttle systems and flight capabilities by satisfying the OFT requirements, is presented. The onorbit portion of the operational flight profile (OFP) for the first Space Transportation System-1 (STS-1) flight is presented. This onorbit document (volume 4) is one in a series that, taken together, will define the STS-1 OFP. This OFP onorbit document represents a combination of the STS-1 ground rules and constraints and the initialization data. The STS-1 flight activities described reflect the trajectory, consumable, crew activity, and flight requirement baseline as of May 1, 1980. Flight plans for the ascent, onorbit, and descent phases of the test flight are presented.

  10. Theoretical studies on vicinal-tetrazine compounds: furoxano-1,2,3,4-tetrazine-1,3,5-trioxide (FTTO-α) and furoxano-1,2,3,4-tetrazine-1,3,7-trioxide (FTTO-β).

    PubMed

    Wang, Tianyi; Zhang, Tao; Xu, Liwen; Wu, Xionghui; Gong, Xuedong; Xia, Mingzhu

    2014-12-01

    The derivatives of 1,2,3,4-tetrazine may be promising candidates of high-energy density compounds and are receiving more and more attention. In this study, two 1,2,3,4-tetrazines, furoxano-1,2,3,4-tetrazine-1,3,5-trioxide (FTTO-α) and furoxano-1,2,3,4-tetrazine-1,3,7-trioxide (FTTO-β), were theoretically studied. The geometrical structures in gas phase were studied at the B3LYP/6-311++G(d,p) level of density functional theory (DFT). The gas phase enthalpies of formation were calculated by the homodesmotic reaction method. The enthalpies of sublimation and solid phase enthalpies of formation were predicted with corrections of electrostatic potential method at the B3PW91/6-31G(d,p) level. The detonation properties were estimated with the Kamlet-Jacobs equations based on the predicted densities and enthalpies of formation in solid state. The available free space in the lattice was calculated to evaluate their stability. Calculations of potential energy surface and structure interconversion thermodynamics under different temperatures were carried out to further confirm their stability. FTTOs have better performance than HMX and FTDO but are easy to decompose to 5,6-dinitroso-v-tetrazine 1,3-dioxide. A synthesis route for FTTO-β was proposed to provide a consideration for the further study. We believe FTTOs could be the key compounds to synthesize other v-tetrazines such as TTTO. PMID:25413679

  11. CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_FM1+FM2+FM3+FM4_Edition1)

    NASA Technical Reports Server (NTRS)

    Wielicki, Bruce A. (Principal Investigator)

    The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2003-12-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

  12. Interconversion of inositol (1,4,5)-trisphosphate to inositol (1,3,4,5)-tetrakisphosphate and (1,3,4)-trisphosphate in permeabilized adrenal glomerulosa cells is calcium-sensitive and ATP-dependent

    SciTech Connect

    Rossier, M.F.; Dentand, I.A.; Lew, P.D.; Capponi, A.M.; Vallotton, M.B.

    1986-08-29

    The metabolism of (/sub 3/H)inositol (1,4,5)-trisphosphate was followed in permeabilized bovine adrenal glomerulosa cells. At low Ca++ concentration (pCa = 7.2), more than 90% of (/sub 3/H)inositol (1,4,5)-trisphosphate had disappeared within 2 min, while two other metabolites, (/sub 3/H)inositol (1,3,4)-trisphosphate and (/sub 3/H)inositol (1,3,4,5)-tetrakisphosphate appeared progressively. At higher Ca++ concentrations (pCa = 5.7 and 4.8), the formation of these two metabolites was markedly increased, but completely abolished if the medium was ATP-depleted. The peak levels for the generation of (/sub 3/H)inositol (1,3,4,5)-tetrakisphosphate (1 min) preceded those of (3H)inositol (1,3,4)-trisphosphate and were closely correlated. These results suggest that, in adrenal glomerulosa cells, the isomer inositol (1,3,4)-trisphosphate is generated from inositol (1,4,5)-trisphosphate via a calcium-sensitive and ATP-dependent phosphorylation/dephosphorylation pathway involving the formation of inositol (1,3,4,5)-tetrakisphosphate.

  13. Synthesis and antifungal activity of 2H-1,4-benzoxazin-3(4H)-one derivatives.

    PubMed

    Śmist, Małgorzata; Kwiecień, Halina; Krawczyk, Maria

    2016-06-01

    A series of 2-alkyl-2H-1,4-benzoxazin-3(4H)-ones (4a-l) was easily synthesized by two-step process involving O-alkylation of 2-nitrophenols with methyl 2-bromoalkanoates and next "green" catalytic reductive cyclization of the obtained 2-nitro ester intermediates (3a-l). Further, 6,7-dibromo (5a-c) and N-acetyl (6) derivatives were prepared by bromination and acetylation of unsubstituted 2-alkyl-2H-1,4-benzoxazin-3(4H)-ones (4a-c). The novel compounds (3a-l, 4d-l, 5a-c and 6) were fully characterized by spectroscopic methods (MS, (1)H and (13)C NMR). 2-Alkyl-2H-1,4-benzoxazin-3(4H)-ones (4a-l, 5a-c and 6) were screened for antifungal activity. Preliminary assays were performed using two methods: in vitro against seven phytopathogenic fungi-Botrytis cinerea, Phythophtora cactorum, Rhizoctonia solani, Phoma betae, Fusarium culmorum, Fusarium oxysporum and Alternaria alternata-and in vivo against barley powdery mildew Blumeria graminis. The tested compounds displayed moderate to good antifungal activity at high concentration (200 mg L(-1)). The most potent compounds were 2-ethyl-2H-1,4-benzoxazin-3(4H)-one (4a), 2-ethyl-7-fluoro-2H-1,4-benzoxazin-3(4H)-one (4g) and 4-acetyl-2-ethyl-2H-1,4-benzoxazin-3(4H)-one (6), which completely inhibited the mycelial growth of seven agricultural fungi at the concentration of 200 mg L(-1) in the in vitro tests. Moreover, 2-ethyl-2H-1,4-benzoxazin-3(4H)-one (4a) and 4-acetyl-2-ethyl-2H-1,4-benzoxazin-3(4H)-one (6) were also screened for antifungal activity at concentrations of 100 mg L(-1) and 20 mg L(-1). In the concentration of 100 mg L(-1), the N-acetyl derivative (6) completely inhibited the growth of three strains of fungi (F. culmorum, P. cactorum and R. solani), while 2-ethyl-2H-1,4-benzoxazin-3(4H)-one (4a) completely inhibited only R. solani strain. At the concentration of 20 mg L(-1), compound 6 showed good activity only against P. cactorum strain (72%). PMID:26963527

  14. Immunologically active (1-->3)-(1-->4)-alpha-D-glucan from Cetraria islandica.

    PubMed

    Olafsdottir, E S; Ingolfsdottir, K; Barsett, H; Paulsen, B S; Jurcic, K; Wagner, H

    1999-03-01

    A polysaccharide, Ci-3, resembling isolichenan except with a much higher degree of polymerization, has been isolated from the water extract, as well as from the alkali extract, of the lichen Cetraria islandica (L.) using ethanol fractionation, dialysis, ion-exchange chromatography and gel filtration. The mean M(r) of Ci-3 was determined to be 2000 kD, compared to 6-8 kD reported for isolichenan. The structure of Ci-3 was elucidated and found to be composed of (1-->3)- and (1-->4)-alpha-D-glucopyranosyl units in the ratio of 2:1, using methanolysis, methylation analysis, optical rotation and NMR spectroscopy. The immunomodulating activity of Ci-3 was tested in an in vitro phagocytosis assay and anti-complementary, and proved to be active in both tests. PMID:10228609

  15. SUZUKI-MIYAURA COUPLING REACTIONS OF 3,5-DICHLORO-1,2,4-THIADIAZOLE

    PubMed Central

    Farahat, Abdelbasset A.; Boykin, David W.

    2014-01-01

    3,5-Dichloro-1,2,4-thiadiazole was allowed to react with different arylboronic acids under different Suzuki-Miyaura coupling conditions: at room temperature 5-aryl-3-chloro-1,2,4-thiadiazoles were obtained and at toluene reflux temperature the products were 3,5-diaryl-1,2,4-thiadiazoles. Sequential coupling reactions lead to 3,5-diaryl-1,2,4-thiadiazoles with non-identical aryl groups. The structure of 3-methoxy-5-(4-methoxyphenyl)-1,2,4-thiadiazole was established from X-ray crystallographic data. PMID:24644388

  16. Crystal structure of benzene-1,3,5-tri-carb-oxy-lic acid-4-pyridone (1/3).

    PubMed

    Staun, Selena L; Oliver, Allen G

    2015-11-01

    Slow co-crystallization of a solution of benzene-1,3,5-tri-carb-oxy-lic acid with a large excess of 4-hy-droxy-pyridine produces an inter-penetrating, three-dimensional, hydrogen-bonded framework consisting of three 4-pyridone and one benzene-1,3,5-tri-carb-oxy-lic acid mol-ecules, C9H6O6·3C5H5NO. This structure represents an ortho-rhom-bic polymorph of the previously reported C-centered, monoclinic structure [Campos-Gaxiola et al. (2014 ▸). Acta Cryst. E70, o453-o454]. PMID:26594492

  17. Synthesis and conformational analysis of phenyl-substituted 1,3,2-oxazaphosphino[4,3- a]- and 1,2,3-oxathiazino[4,3- a]isoquinolines

    NASA Astrophysics Data System (ADS)

    Schuster, Ildikó; Koch, Andreas; Heydenreich, Matthias; Kleinpeter, Erich; Lázár, László; Fülöp, Ferenc

    2008-10-01

    Through the ring closures of tetrahydroisoquinoline 1,3-amino alcohols bearing a phenyl group in the side-chain, diastereomers of novel 1- or 2-phenyl-substituted 1,3,2-oxazaphosphino[4,3- a]isoquinoline 4-oxides, and 1,2,3-oxathiazino[4,3- a]isoquinoline 4-oxides and 4,4-dioxides were prepared. NMR analysis and DFT calculations on the prepared tetrahydroisoquinoline-condensed 1,2,3-heterocycles revealed that their conformational equilibria of cis 1-trans-cis 2 type are influenced by the relative configuration of P-4 in the 1,3,2-oxazaphosphinanes, and by the position of the phenyl group in the 1,2,3-oxathiazines.

  18. Capacity improvement by deficit of transition metals in inverse spinel LiNi1/3Co1/3Mn1/3VO4 cathodes

    NASA Astrophysics Data System (ADS)

    Kitajou, Ayuko; Yoshida, Jun; Nakanishi, Shinji; Matsuda, Yasuaki; Kanno, Ryoji; Okajima, Toshihiro; Okada, Shigeto

    2016-01-01

    Although inverse spinel materials have attracted attention because of their unusually high voltage characteristics, their rechargeable capacities are generally less than 50 mAh g-1, as a result of the coexistence of Li and transition metal ions at 16d octahedral sites. This work attempted to improve cathode functioning by optimizing the quantities of Li and transition metal ions residing at the 16d sites of LiNi1/3Co1/3Mn1/3VO4. The rechargeable capacity of the LiNi0.28Co0.28Mn0.26V0.80O4 synthesized in the present study was found to be above 120 mAh g-1, representing the largest capacity reported to date for an inverse spinel material. The results of in-situ XANES analysis demonstrated that the charge-discharge reactions of LiNi1/3Co1/3Mn1/3VO4 corresponds to the Mn2+/Mn4+ and Co2+/Co3+ redox couples, mainly.

  19. 1,1,4,4-Tetra-tert-butyl-1,4-dichloro-2,2,3,3-tetra-phenyl-tetra-silane.

    PubMed

    Otsuka, Kyohei; Ishida, Shintaro; Kyushin, Soichiro

    2012-02-01

    The title compound, C(40)H(56)Cl(2)Si(4), was synthesized by the coupling of 1,1-di-tert-butyl-1,2-dichloro-2,2-diphenyl-disilane with lithium. The asymmetric unit contains one half-mol-ecule, which is completed by an inversion centre. In the mol-ecule, the tetra-silane skeleton adopts a perfect anti conformation and the Si-Si bonds [2.4355 (5) and 2.4328 (7) Å] are longer than the standard Si-Si bond length (2.34 Å). The Si-Si-Si angle [116.09 (2)°] is larger than the tetra-hedral bond angle (109.5°). These long bond lengths and the wide angle are favorable for reducing the steric hindrance among the tert-butyl and the phenyl groups. The dihedral angle between the phenyl rings in the asymmetric unit is 37.36 (8)°. PMID:22347038

  20. 1,1,4,4-Tetra-tert-butyl-1,4-dichloro-2,2,3,3-tetra­phenyl­tetra­silane

    PubMed Central

    Otsuka, Kyohei; Ishida, Shintaro; Kyushin, Soichiro

    2012-01-01

    The title compound, C40H56Cl2Si4, was synthesized by the coupling of 1,1-di-tert-butyl-1,2-dichloro-2,2-diphenyl­disilane with lithium. The asymmetric unit contains one half-mol­ecule, which is completed by an inversion centre. In the mol­ecule, the tetra­silane skeleton adopts a perfect anti conformation and the Si—Si bonds [2.4355 (5) and 2.4328 (7) Å] are longer than the standard Si—Si bond length (2.34 Å). The Si—Si—Si angle [116.09 (2)°] is larger than the tetra­hedral bond angle (109.5°). These long bond lengths and the wide angle are favorable for reducing the steric hindrance among the tert-butyl and the phenyl groups. The dihedral angle between the phenyl rings in the asymmetric unit is 37.36 (8)°. PMID:22347038

  1. Chemically induced Parkinson's disease: intermediates in the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the 1-methyl-4-phenyl-pyridinium ion

    SciTech Connect

    Chacon, J.N.; Chedekel, M.R.; Land, E.J.; Truscott, T.G.

    1987-04-29

    Various unstable intermediate oxidation states have been postulated in the metabolic activation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the 1-methyl-4-phenyl pyridinium ion. We now report the first direct observation of these free radical intermediates by pulse radiolysis and flash photolysis. Studies are described of various reactions of such species, in particular with dopamine whose autoxidation to dopamine quinone is reported to be potentiated by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine.

  2. Formal Asymmetric (4+1) Annulation Reaction between Sulfur Ylides and 1,3-Dienes.

    PubMed

    Rousseau, Olivier; Delaunay, Thierry; Dequirez, Geoffroy; Trieu-Van, Tran; Robeyns, Koen; Robiette, Raphaël

    2015-09-01

    A highly enantioselective synthesis of functionalized cyclopentanoids by a formal asymmetric (4+1) annulation strategy was developed. The methodology consists of a stereoselective cyclopropanation reaction between chiral sulfur ylides and 1,3-dienes followed by a, in situ, stereospecific MgI2 -catalyzed rearrangement of vinylcyclopropanes. This method is distinguished by a remarkable compatibility with functional groups and a high stereocontrol. PMID:26235566

  3. Crystal structure of 4-[(E)-(4-fluoro­benzyl­idene)amino]-3-methyl-1H-1,2,4-triazole-5(4H)-thione

    PubMed Central

    Manjula, P. S.; Sarojini, B. K.; Narayana, B.; Byrappa, K.; Madan Kumar, S.

    2015-01-01

    The title compound, C10H9FN4S, crystallizes with two mol­ecules (A and B) in the asymmetric unit. The dihedral angle between the planes of the trizole and fluoro­benzene rings is 7.3 (3)° in mol­ecule A and 41.1 (3)° in mol­ecule B. Mol­ecule A features an intra­molecular C—H⋯S hydrogen bond, which closes an S(6) ring. In the crystal, A+B dimers linked by pairs of N—H⋯S hydrogen bonds occur, generating R 2 2(8) loops. Weak π–π stacking contacts [centroid–centroid separation = 3.739 (6) Å] are also observed. PMID:26870523

  4. Synthesis and Antimicrobial Activity of Some New 2-(3-(4-Aryl)-1-phenyl-1H-pyrazol-4-yl) Chroman-4-ones.

    PubMed

    Prakash, O; Hussain, K; Aneja, K R; Sharma, C

    2011-09-01

    Seven new 2-(3-(4-aryl)-1-phenyl-1H-pyrazol-4-yl) chroman-4-ones (4a-4g) have been synthesized by cyclization of 2-hydroxychalcone analogues of pyrazole 3a-3g using conc. HCl in acetic acid. The structures of the compounds 4a-4g were established by the combined use of (1)HNMR, IR and mass spectra. All the seven compounds were tested in vitro for their antibacterial activity against two Gram positive bacteria namely Staphylococcus aureus and Bacillus subtilis and two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. The compounds 4b, 4c, 4e, 4f, 4g have displayed good antibacterial activity when compared with commercially available antibiotic, ciprofloxacin. These compounds also were screened for their antifungal activity against two ear pathogenic fungi, namely Aspergillus Niger and A. flavus. The compounds 4a, 4c, 4d, 4g exhibited good antifungal activity when compared with commercially available antifungal, fluconazole. PMID:22923876

  5. Synthesis and Antimicrobial Activity of Some New 2-(3-(4-Aryl)-1-phenyl-1H-pyrazol-4-yl) Chroman-4-ones

    PubMed Central

    Prakash, O.; Hussain, K.; Aneja, K. R.; Sharma, C.

    2011-01-01

    Seven new 2-(3-(4-aryl)-1-phenyl-1H-pyrazol-4-yl) chroman-4-ones (4a-4g) have been synthesized by cyclization of 2-hydroxychalcone analogues of pyrazole 3a-3g using conc. HCl in acetic acid. The structures of the compounds 4a-4g were established by the combined use of 1HNMR, IR and mass spectra. All the seven compounds were tested in vitro for their antibacterial activity against two Gram positive bacteria namely Staphylococcus aureus and Bacillus subtilis and two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. The compounds 4b, 4c, 4e, 4f, 4g have displayed good antibacterial activity when compared with commercially available antibiotic, ciprofloxacin. These compounds also were screened for their antifungal activity against two ear pathogenic fungi, namely Aspergillus Niger and A. flavus. The compounds 4a, 4c, 4d, 4g exhibited good antifungal activity when compared with commercially available antifungal, fluconazole. PMID:22923876

  6. Molecular and crystal structure of 3-benzyl-4-(4-carboxyphenyl)-4,5-dihydro-1 H-1,2,4-triazol-5-one

    NASA Astrophysics Data System (ADS)

    Tanak, H.

    2014-12-01

    The molecular structure of the title compound C16H13N3O3 was characterized by single crystal X-ray diffraction method. The compound crystallizes in the triclinic space group with Z = 4 in the unit cell. In the asymmetric unit of the title compound, there are two crystallographically independent molecules, designated A and B. In the crystal structure, the phenyl and benzoic acid ring systems are bridged by 1,2,4-triazole ring for both independent molecules. The ring systems are perfectly planar for both molecules but the whole molecule is not planar. The crystal structure is stabilized by N-H⋯O and O-H⋯O type classical intermolecular hydrogen bonds. In the crystal, N-H⋯O and O-H⋯O hydrogen bonds link the molecules into one-dimensional infinite chains along direction. The crystal packing is also stabilized by C-H⋯π interactions.

  7. Conformational analysis, intramolecular hydrogen bonding, and vibrational assignment of 4,4-dimethyl-1-phenylpentane-1,3-dione

    NASA Astrophysics Data System (ADS)

    Afzali, R.; Vakili, M.; Tayyari, S. F.; Eshghi, H.; Nekoei, A.-R.

    2014-01-01

    Molecular structure, conformational stabilities, and intramolecular hydrogen bonding (IHB) of 4,4-dimethyl-1-phenylpentane-1,3-dione (DMPD), have been investigated by means of density functional theory (DFT) calculations and experimental results. The geometries and electronic energies of different cis-enol forms of DMPD have been obtained with the ab initio (MP2 level) and DFT (B3LYP and TPSSh levels) methods, using various basis sets. The energy differences between three stable E1, E2, and E3 chelated enol forms are negligible. According to the theoretical calculations, DMPD has a hydrogen bond strength of about 16.8 kcal/mol, calculated at the B3LYP/6-311++G** level, which is about 0.7 kcal/mol stronger than that of benzoylacetone (BA). The theoretical and experimental results obtained for stable enol forms of DMPD have been compared with each other and also with those of BA and 5,5-dimethylhexane-2,4-dione (DMHD). The molecular stability and the hydrogen bond strength were investigated by applying the NBO, topological analysis, geometry calculations, and spectroscopic results.

  8. Antigenic and 3D structural characterization of soluble X4 and hybrid X4-R5 HIV-1 Env trimers

    PubMed Central

    2014-01-01

    Background HIV-1 is decorated with trimeric glycoprotein spikes that enable infection by engaging CD4 and a chemokine coreceptor, either CCR5 or CXCR4. The variable loop 3 (V3) of the HIV-1 envelope protein (Env) is the main determinant for coreceptor usage. The predominant CCR5 using (R5) HIV-1 Env has been intensively studied in function and structure, whereas the trimeric architecture of the less frequent, but more cytopathic CXCR4 using (X4) HIV-1 Env is largely unknown, as are the consequences of sequence changes in and near V3 on antigenicity and trimeric Env structure. Results Soluble trimeric gp140 Env constructs were used as immunogenic mimics of the native spikes to analyze their antigenic properties in the context of their overall 3D structure. We generated soluble, uncleaved, gp140 trimers from a prototypic T-cell line-adapted (TCLA) X4 HIV-1 strain (NL4-3) and a hybrid (NL4-3/ADA), in which the V3 spanning region was substituted with that from the primary R5 isolate ADA. Compared to an ADA (R5) gp140, the NL4-3 (X4) construct revealed an overall higher antibody accessibility, which was most pronounced for the CD4 binding site (CD4bs), but also observed for mAbs against CD4 induced (CD4i) epitopes and gp41 mAbs. V3 mAbs showed significant binding differences to the three constructs, which were refined by SPR analysis. Of interest, the NL4-3/ADA construct with the hybrid NL4-3/ADA CD4bs showed impaired CD4 and CD4bs mAb reactivity despite the presence of the essential elements of the CD4bs epitope. We obtained 3D reconstructions of the NL4-3 and the NL4-3/ADA gp140 trimers via electron microscopy and single particle analysis, which indicates that both constructs inherit a propeller-like architecture. The first 3D reconstruction of an Env construct from an X4 TCLA HIV-1 strain reveals an open conformation, in contrast to recently published more closed structures from R5 Env. Exchanging the X4 V3 spanning region for that of R5 ADA did not alter the open

  9. Reactions of organyl and silyl alanes with 1,3,4,5,6-pentamethyl-2-aminoborazine.

    PubMed

    Fan, Maomin; Duesler, Eileen N; Nöth, Heinrich; Paine, Robert T

    2010-03-15

    The reactions of (Me(3)Si)(3)Al, Me(3)Al, Et(3)Al, and i-Bu(3)Al with 1,3,4,5,6-pentamethyl-2-aminoborazine have been examined. An amine alane adduct (Me(3)Si)(3)Al.NH(2)B(3)(Me)(2)N(3)Me(3) (1) and several elimination products [(Me(3)Si)(2)AlN(H)B(3)(Me)(2)N(3)Me(3)](2) (2), [(Me(3)SiAl)(4)(Me(3)SiN)(3)NH] (3), [Me(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (4), [Et(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (5), and [i-Bu(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (6) have been isolated. Compounds 1, 2, 4-6 have been spectroscopically characterized, and single crystal X-ray diffraction structure determinations have been completed for 1-4 and 6. The molecular chemistry provides insight into the reaction of Me(3)Al and 1,3,5-N-trimethyl-2,4,6-B-triaminoborazine that, upon pyrolysis, produces AlN/BN composite ceramic materials. PMID:20158196

  10. Benchmarking ENDF/B-VII.1, JENDL-4.0 and JEFF-3.1

    SciTech Connect

    Van Der Marck, S. C.

    2012-07-01

    Three nuclear data libraries have been tested extensively using criticality safety benchmark calculations. The three libraries are the new release of the US library ENDF/B-VII.1 (2011), the new release of the Japanese library JENDL-4.0 (2011), and the OECD/NEA library JEFF-3.1 (2006). All calculations were performed with the continuous-energy Monte Carlo code MCNP (version 4C3, as well as version 6-beta1). Around 2000 benchmark cases from the International Handbook of Criticality Safety Benchmark Experiments (ICSBEP) were used. The results were analyzed per ICSBEP category, and per element. Overall, the three libraries show similar performance on most criticality safety benchmarks. The largest differences are probably caused by elements such as Be, C, Fe, Zr, W. (authors)

  11. 3-Acetyl-5-phenyl-1-p-tolyl-1H-pyrazole-4-carbonitrile

    PubMed Central

    Abdel-Aziz, Hatem A.; Ghabbour, Hazem A.; Chantrapromma, Suchada; Fun, Hoong-Kun

    2012-01-01

    In the title pyrazole derivative, C19H15N3O, the central pyrazole ring makes dihedral angles of 42.71 (9) and 61.34 (9)°, respectively, with the phenyl and p-tolyl rings. The dihedral angle between the phenyl and p-tolyl rings is 58.22 (9)°. The 3-acetyl-1H-pyrazole-4-carbonitrile unit is essentially planar, with an r.m.s. deviation of 0.0295 (1) Å for the ten non-H atoms. PMID:22606111

  12. 5-(4-Fluoro-benzyl-idene)-2,2-dimethyl-1,3-dioxane-4,6-dione.

    PubMed

    Zeng, Wu-Lan

    2010-01-01

    The title compound, C(13)H(11)FO(4), was prepared by the reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione and 4-fluoro-benz-alde-hyde in ethanol. The 1,3-dioxane ring adopts an envelope conformation. The crystal structure is stabilized by weak inter-molecular C-H⋯O hydrogen bonds. PMID:21588707

  13. Is inositol (1,3,4,5)-tetrakisphosphate a new second messenger

    SciTech Connect

    Hansen, C.A.; Williamson, J.R.

    1986-05-01

    Hormone-stimulated hydrolysis of inositol (Ins) lipids results in the rapid formation of Ins(1,4,5)P/sub 3/, the second messenger for intracellular Ca/sup 2 +/ mobilization. Recently, a more polar inositol phosphate, Ins(1,3,4,5)P/sub 4/ as well as its probable hydrolysis product Ins(1,3,4)P/sub 3/ have been reported to accumulate in carbachol-stimulated brain slices. Vasopressin addition to hepatocytes prelabeled with (/sup 3/H)-Ins also showed a rapid increase of Ins(1,3,4,5)P/sub 4/, which was similar to that of Ins(1,4,5)P/sub 3/, while the accumulation of Ins(1,3,4)P/sub 3/ was slower. In order to examine whether Ins(1,3,4,5)P/sub 4/ has any functional effects on Ca/sup 2 +/ homeostasis, it was synthesized enzymatically from (/sup 3/H)-Ins(1,4,5)P/sub 3/ using a partially purified phosphoinositol kinase activity from rat brain cortex. (/sup 3/H)-labeled inositol phosphates were separated by anion exchange chromatography and analyzed by HPLC using ammonium formate/phosphoric acid gradient elution. Preliminary experiments indicate that Ins(1,3,4,5)P/sub 4/ up to 10 ..mu..M does not release Ca/sup 2 +/ from vesicular pools in saponin-permeabilized hepatocytes. It has a slight inhibitory effect on Ins(1,4,5)P/sub 3/-induced Ca/sup 2 +/ release. The effect of Ins(1,3,4,5)P/sub 4/ on plasma membrane Ca/sup 2 +/ fluxes are presently being investigated.

  14. The 3-3-1 model with A{sub 4} flavor symmetry

    SciTech Connect

    Dong, P. V.; Hue, L. T.; Long, H. N.; Soa, D. V.

    2010-03-01

    We argue that the A{sub 4} symmetry as required by three flavors of fermions may well-embed in the SU(3){sub C} x SU(3){sub L} x U(1){sub X} gauge model. The new neutral fermion singlets as introduced in a canonical seesaw mechanism can be combined with the standard model lepton doublets to perform SU(3){sub L} triplets. Various leptoscalar multiplets such as singlets, doublets, and triplets as played in the models of A{sub 4} are unified in single SU(3){sub L} antisextets. As a result, naturally light neutrinos with various kinds of mass hierarchies are obtained as a combination of type I and type II seesaw contributions. The observed neutrino mixing pattern in terms of the Harrison-Perkins-Scott proposal is obtained by enforcing the A{sub 4} group. The quark masses and Cabibbo-Kobayashi-Maskawa mixing matrix are also discussed. By virtue of very heavy antisextets, the nature of the vacuum alignments of scalar fields can be given.

  15. Anisotropic Molecular Orientation of Poly [4, 4'-oxydiphenylene- 1, 2, 3, 4-cyclobutanetetracarboximide] Films Irradiated by Linearly Polarized UV Light

    NASA Astrophysics Data System (ADS)

    Sakamoto, Kenji; Usami, Kiyoaki; Araya, Takeshi; Ushioda, Sukekatsu

    1999-12-01

    We have investigated the anisotropic molecular orientation of poly [4, 4'-oxydiphenylene-1, 2, 3, 4-cyclobutanetetracarboximide] (CBDA-ODA) films induced by irradiation with linearly polarized ultraviolet light (LPUVL). The molecular orientation was monitored by measuring the polarized infrared (IR) absorption spectra of a 10-nm-thick film. The anisotropy of the molecular orientation exceeded that of a rubbed film with the same film thickness. From the LPUVL exposure dependence of IR absorption we found that preferential cleavage occurs to the cyclobutane ring in the polyimide backbone structure oriented parallel to the polarization direction of LPUVL. Then the orientation of the cleaved polyimide molecule is randomized. We conclude that the large anisotropy of the LPUVL-exposed film is caused by the anisotropic cleavage of the cyclobutane rings and the orientational randomization of the cleaved polyimide molecules.

  16. Expression of NR1I3 in mouse lung tumors induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone

    PubMed Central

    Fukumasu, H.; Cordeiro, Y.G.; Rochetti, A.L.; Barra, C.N.; Sámora, T.S.; Strefezzi, R.F.; Dagli, M.L.Z.

    2015-01-01

    Nuclear receptor subfamily 1, group I, member 3 (NR1I3) is reported to be a possible novel therapeutic target for some cancers, including lung, brain and hematopoietic tumors. Here, we characterized expression of NR1I3 in a mouse model of lung carcinogenesis induced by 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone (NNK), the most potent tobacco carcinogen. Lung tumors were collected from mice treated with NNK (400 mg/kg) and euthanized after 52 weeks. Benign and malignant lesions were formalin-fixed and paraffin-embedded for histology and immunohistochemistry, with samples snap-frozen for mRNA analysis. Immunohistochemically, we found that most macrophages and type I and II pneumocytes expressed NR1I3, whereas fibroblasts and endothelial cells were NR1I3−. Compared with benign lesions, malignant lesions had less NR1I3+ tumor cells. Gene expression analysis also showed an inverse correlation between NR1I3 mRNA expression and tumor size (P=0.0061), suggesting that bigger tumors expressed less NR1I3 transcripts, in accordance with our immunohistochemical NR1I3 tests. Our results indicate that NR1I3 expression decreased during progression of malignant lung tumors induced by NNK in mice. PMID:25714878

  17. Entry of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into the rat brain

    SciTech Connect

    Riachi, N.J.; LaManna, J.C.; Harik, S.I.

    1989-06-01

    We studied blood-to-brain entry of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium (MPP+) and butanol in anesthetized rats using the indicator-fractionation method with right atrial bolus injection. Minimal amounts of MPP+, which has low octanol/water partition coefficient, crossed the blood-brain barrier. MPTP and butanol, both of which have high octanol/water partition coefficients, were almost completely extracted by all regions of the brain on the first pass. The main difference between the MPTP and butanol tracers is that butanol rapidly left the brain with an exponential rate constant of 1.24 min-1, whereas MPTP was avidly retained by the brain with a washout rate constant of 0.10 min-1 (mean values for the four brain regions that we studied). Early retention of MPTP by the brain was not due to its rapid metabolism by monoamine oxidase because pargyline pretreatment did not affect this rate constant. However, 30 min after (/sup 3/H)MPTP injection, brain retention of the 3H tracer was reduced significantly by pargyline treatment, and the ratio of brain MPTP/MPP+ was increased markedly.

  18. Controlling stereoselectivity by enzymatic and chemical means to access enantiomerically pure (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinoline derivatives☆

    PubMed Central

    Orden, Alejandro A.; Schrittwieser, Joerg H.; Resch, Verena; Mutti, Francesco G.; Kroutil, Wolfgang

    2013-01-01

    A chemoenzymatic strategy for the synthesis of enantiomerically pure novel alkaloids (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinolines is presented. The key steps are the biocatalytic stereoselective reductive amination of substituted 1-phenylpropan-2-one derivatives to yield chiral amines employing microbial ω-transaminases, and the diastereoselective reduction of a Bischler–Napieralski imine intermediate by catalytic hydrogenation in the presence of palladium on charcoal, leading exclusively to the desired cis-isomer. PMID:24503964

  19. Phosphate Ca1/4Sr1/4Zr2(PO4)3 of the NaZr2(PO4)3 structure type: Synthesis of a dense ceramic material and its radiation testing

    NASA Astrophysics Data System (ADS)

    Orlova, A. I.; Volgutov, V. Yu.; Mikhailov, D. A.; Bykov, D. M.; Skuratov, V. A.; Chuvil'deev, V. N.; Nokhrin, A. V.; Boldin, M. S.; Sakharov, N. V.

    2014-03-01

    The powder of phosphate Ca1/4Sr1/4Zr2(PO4)3 was synthesized by sol-gel processes in the presence of citric acid and ethylene glycol. Ceramic samples were prepared from this powder by Spark Plasma Sintering (SPS), their relative densities were found to be 99.5 ± 0.3% after the isothermal treatment at 860 °С for 3 min.

  20. Synthesis of 1,4,5,6-tetrahydropyridine derivatives starting from trans-3-chloro-1,3-alkadien-5-ones

    SciTech Connect

    Melikyan, G.G.; Atanesyan, K.A.; Aslanyan, G.Kh.; Tirakyan, M.R.; Khachatryan, L.A.; Badanyan, Sh.O.

    1987-10-01

    A method has been developed for the synthesis of 3-carbethoxy-2-methyl-6-(oxo-alkylidene)-1,4,5,6-tetrahydropyridines by reaction of trans-3-chloro-1,3-alkadien-5-ones with ethyl aminocrotonate. It is shown that the corresponding vinylacetylanic ketones are intermediate products of the reactions. PMR spectra in CCl/sub 4/ were obtained on a Perkin-Elmer R12B (60 MHz) spectrometer, with TMS as internal standard. /sup 13/C NMR spectra were recordeed on a Bruker WH-90 instrument (22.63 MHz) without suppression and with complete suppression of spin-spin coupling. IR spectra were recorded in CCl/sub 4/ on a UR-10 instrument, mass spectra were recorded on a MX-1303 spectrometer with electron ionization energy of 30 eV.

  1. A predictive 3-3-1 model with A4 flavor symmetry

    NASA Astrophysics Data System (ADS)

    Cárcamo Hernández, A. E.; Martinez, R.

    2016-04-01

    We propose a predictive model based on the SU (3)C ⊗ SU (3)L ⊗ U(1)X gauge group supplemented by the A4 ⊗Z3 ⊗Z4 ⊗Z6 ⊗Z16 discrete group, which successfully describes the SM fermion mass and mixing pattern. The small active neutrino masses are generated via inverse seesaw mechanism with three very light Majorana neutrinos. The observed charged fermion mass hierarchy and quark mixing pattern are originated from the breaking of the Z4 ⊗Z6 ⊗Z16 discrete group at very high scale. The obtained values for the physical observables for both quark and lepton sectors are in excellent agreement with the experimental data. The model predicts a vanishing leptonic Dirac CP violating phase as well as an effective Majorana neutrino mass parameter of neutrinoless double beta decay, with values mββ = 2 and 48 meV for the normal and the inverted neutrino mass hierarchies, respectively.

  2. Synthesis of 3-Methyl-4-(4-methylbenzoyl)-1-phenyl-pyrazol-5-One: How to Avoid O-Acylation

    ERIC Educational Resources Information Center

    Kurteva, Vanya B.; Petrova, Maria A.

    2015-01-01

    In this laboratory experiment, students synthesize 3-methyl-4-(4-methylbenzoyl)-1-phenyl-pyrazol-5-one by selective C-acylation of 3-methyl-1-phenyl-1H-pyrazol-5-one. Calcium hydroxide is used to push the tautomeric equilibrium toward the enol form, to protect the hydroxyl functionality as a complex, to trap the liberated hydrogen chloride, and to…

  3. Synthesis and pharmacological properties of 1-(4-substituted)butyl derivatives of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimi dine-5 -carboxylic acid.

    PubMed

    Sladowska, H; Sieklucka-Dziuba, M; Rejdak, R; Kleinrok, Z

    2000-01-01

    The synthesis of 1-(4-substituted)butyl derivatives of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimid ine-5- carboxylic acid and the results of the preliminary pharmacological screening are described in this paper. Some of them showed a weak analgesic action and caused suppression of the spontaneous locomotor activity of mice. PMID:10755225

  4. 26 CFR 1.702-3T - 4-Year spread (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false 4-Year spread (temporary). 1.702-3T Section 1.702-3T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Partners and Partnerships § 1.702-3T 4-Year spread (temporary). (a) Applicability. This section applies to...

  5. Molecular structures of antiviral agents, 2,3-dihydroxybenzaldehyde 2,4-dinitrophenylhydrazone and 4-[(4-methylpiperazin-1-yl)imino]methyl-1,2-benzodiol

    SciTech Connect

    Gurskaya, G. V.; Zavodnik, V. E.; Zhukhlistova, N. E.; Kozlov, M. V.

    2008-07-15

    Two antiviral agents, namely, 2,3-dihydroxybenzaldehyde 2,4-dinitrophenylhydrazone and 4-[(4-methylpiperazin-1-yl)imino]methyl-1,2-benzodiol, are studied by X-ray diffraction. The stereochemical features of the molecular structures of the compounds under investigation are discussed, and the possible correlation between the structure and biological activity with respect to hepatitis C virus RNA-dependent RNA polymerase is analyzed.

  6. STS-109 Mission Highlights Resource Tape. Part 1 of 4; Flight Days 1 - 3

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This video, Part 1 of 4, shows the activities of the STS-109 crew (Scott Altman, Commander; Duane Carey, Pilot; John Grunsfeld, Payload Commander; Nancy Currie, James Newman, Richard Linnehan, Michael Massimino, Mission Specialists) during flight days 1 through 3. The activities from other flight days can be seen on 'STS 109 Mission Highlights Resource Tape' Part 2 of 4 (internal ID 2002137664), 'STS 109 Mission Highlights Resource Tape' Part 3 of 4 (internal ID 2002139471), and 'STS-109 Mission Highlights Resource Tape' Part 4 of 4 (internal ID 2002137577). The main activity recorded during flight day 1 is the liftoff of Columbia. Attention is given to suit-up, boarding, and pre-flight procedures. The pre-launch crew meal has no sound. The crew members often wave to the camera before liftoff. The jettisoning of the solid rocket boosters is shown, and the External Tank is seen as it falls to Earth, moving over African dunes in the background. There are liftoff replays, including one from inside the cockpit. The opening of the payload bay doors is seen from the rear of the shuttle's cockpit. The footage from flight day 2 shows the Flight Support System for bearthing the HST (Hubble Space Telescope). Crew preparations for the bearthing are shown. Flight day 3 shows the tracking of and approach to the HST by Columbia, including orbital maneuvers, the capture of the HST, and its lowering onto the Flight Support System. Many views of the HST are shown, including one which reveals an ocean and cloud background as the HST retracts a solar array.

  7. Synthesis and Antimicrobial Activity of Bis-[4-methoxy-3-(6-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]-thiadiazin-3-yl)phenyl]methanes and Bis-[(triazolo[3,4-b]thiadiazipin-3-yl)phenyl]methanes.

    PubMed

    Srinivas, Avula

    2016-01-01

    A series of novel Bis-[4-methoxy-3-(6-aryl-7H-[1,2,4]tria zolo[3,4-b][1,3,4]-thiadiazin-3-yl)phenyl]methanes and Bis-[(triazolo[3,4-b]thiadiazipin-3-yl)phenyl]methanes ( 5a-e & 6a-e ) has been synthesized and characterized by IR, (1)H NMR, (13)C NMR, MS and elemental analysis. All the newly synthesized compounds were screened for their antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Klobsinella aerogenes and Chromobacteriumviolaceum and antifungal activity against Candida albicans, Aspergillus fumigatus, Trichophyton rubrum and Trichophyton mentagrophytes. Compounds 5b, 5d,5e, 6b, 6c and 6e exhibited potent activity against the test bacteria and fungi, and emerged as potential molecules for further development. PMID:26970802

  8. Synthesis, Antimitotic and Antivascular Activity of 1-(3′,4′,5′-Trimethoxybenzoyl)-3-arylamino-5-amino-1,2,4-triazoles

    PubMed Central

    Romagnoli, Romeo; Baraldi, Pier Giovanni; Salvador, Maria Kimatrai; Prencipe, Filippo; Bertolasi, Valerio; Cancellieri, Michela; Brancale, Andrea; Hamel, Ernest; Castagliuolo, Ignazio; Consolaro, Francesca; Porcú, Elena; Basso, Giuseppe; Viola, Giampietro

    2014-01-01

    A new class of compounds that incorporated the structural motif of the 1-(3′,4′,5′-trimethoxtbenzoyl)-3-arylamino-5-amino-1,2,4-triazole molecular skeleton was synthesized and evaluated for their antiproliferative activity in vitro, interactions with tubulin, and cell cycle effects. The most active agent, 3c, was evaluated for antitumor activity in vivo. Structure-activity relationships were elucidated with various substituents on the phenyl ring of the anilino moiety at the C-3 position of the 1,2,4-triazole ring. The best results for inhibition of cancer cell growth were obtained with the p-Me, m,p-diMe, and p-Et phenyl derivatives 3c, 3e, and 3f, respectively, and overall, these compounds were more or less as active as CA-4. Their vascular disrupting activity was evaluated in HUVEC cells, with compound 3c showing activity comparable with that of CA-4. Compound 3c almost eliminated the growth of syngeneic hepatocellular carcinoma in Balb/c mice, suggesting that 3c could be a new antimitotic agent with clinical potential. PMID:25025853

  9. GBF1- and ACBD3-Independent Recruitment of PI4KIIIβ to Replication Sites by Rhinovirus 3A Proteins

    PubMed Central

    Dorobantu, Cristina M.; Ford-Siltz, Lauren A.; Sittig, Simone P.; Lanke, Kjerstin H. W.; Belov, George A.; van der Schaar, Hilde M.

    2014-01-01

    PI4KIIIβ recruitment to Golgi membranes relies on GBF1/Arf and ACBD3. Enteroviruses such as poliovirus and coxsackievirus recruit PI4KIIIβ to their replication sites via their 3A proteins. Here, we show that human rhinovirus (HRV) 3A also recruited PI4KIIIβ to replication sites. Unlike other enterovirus 3A proteins, HRV 3A failed to bind GBF1. Although HRV 3A was previously shown to interact with ACBD3, our data suggest that PI4KIIIβ recruitment occurred independently of both GBF1 and ACBD3. PMID:25410869

  10. Outcomes of the 5-4-3-2-1 Go Childhood Obesity Community Trial

    ERIC Educational Resources Information Center

    Evans, W. Douglas; Christoffel, Katherine K.; Necheles, Jonathan; Becker, Adam B.; Snider, Jeremy

    2011-01-01

    Objectives: To determine effects of the "5-4-3-2-1 Go" community social marketing campaign on obesity risk factors. Methods: We randomly assigned 524 parents of 3- to 7-year-old children to receive "5-4-3-2-1 Go" counseling or not. We surveyed parents about "5-4-3-2-1 Go!" behaviors and perceptions of children's behaviors at baseline and one year…

  11. 2-{4-[(1,3-Benzodioxol-5-yl)meth-yl]piperazin-1-yl}pyrimidine.

    PubMed

    Wu, Chunli; Li, Jieming; Wei, Huijie; Hang, Ye; Jiang, Yueming

    2013-01-01

    In the title compound, C16H18N4O2, known also as peribedil, the dihedral angle between the mean planes of the pyrimidine and benzene rings is 56.5 (8)°. The 1,3-dioxole fragment adopts an envelope conformation with the methyl-ene C atom forming the flap; this atom deviates by 0.232 (3) Å from the plane defined by the remaining atoms of the 1,3-benzodioxole unit. In the crystal, C-H⋯π inter-actions between c-glide-related mol-ecules arrange them into columns extending along the c-axis direction. The columns related by a unit translation along the b axis are packed into (100) layers via another C-H⋯π inter-action involving the pyrimidine ring as an acceptor. PMID:24046690

  12. Enhanced Sinterability and Microwave Dielectric Performance of (1 - x)ZnAl2O4- xLi4/3Ti5/3O4 Ceramics

    NASA Astrophysics Data System (ADS)

    Wang, Nan; Zhou, Huanfu; Gong, Jianzhang; Fan, Guangchao; Chen, Xiuli

    2016-06-01

    (1 - x)ZnAl2O4- xLi4/3Ti5/3O4 (ZALT) ( x = 0.2, 0.4, 0.6, 0.8) microwave dielectric ceramics were prepared by a solid state reaction method. The preparation, sintering behavior, phase composition and microwave dielectric properties of ZALT ceramics were investigated. ZnAl2O4 could not form a solid solution with Li4Ti5O12. With x increasing from 0.2 to 0.8, the phase compositions of ZALT ceramics changed: (ZnAl2O4 and Li2ZnTi3O8, x = 0.2, 0.4) → (ZnAl2O4, Li2ZnTi3O8 and Li4Ti5O12, x = 0.6) → (Li2ZnTi3O8 and Li4Ti5O12, x = 0.8), and the main phase changed from ZnAl2O4 ( x = 0.2, 0.4) to Li2ZnTi3O8 ( x = 0.6, 0.8). With increasing x values, the sintering temperature was reduced from 1250°C to 1100°C. ZALT ceramics exhibited microwave dielectric properties with ɛ r of 13.0-29.0, Q × f values of 30,220-65,580 GHz and τ f values of -51.4 ppm/°C to -20.9 ppm/°C.

  13. High coverage hydrogen adsorption on the Fe3O4(1 1 0) surface

    NASA Astrophysics Data System (ADS)

    Yu, Xiaohu; Zhang, Xuemei; Wang, Shengguang

    2015-10-01

    Hydrogen adsorption on the A and B termination layers of the Fe3O4(1 1 0) surface at different coverage has been systematically studied by density functional theory calculations including an on-site Hubbard term (GGA + U). The adsorption of hydrogen prefers surface oxygen atoms on both layers. The more stable A layer has stronger adsorption energy than the less stable B layer. The saturation coverage has two dissociatively adsorbed H2 on the A layer, and one dissociatively adsorbed H2 on the B layer. The adsorption mechanism has been analyzed on the basis of projected density of states (PDOS).

  14. NMR study on cis-N-[4-[4-(1,2-benzisozole-3-yl)-1-piperazinyl] butyl]cyclohexane-1,2-dicarboximide monohydrochloride dihydrate.

    PubMed

    Feng, Yongbin; Lin, Jimao; Lin, Zhenguang; Li, Hongmei

    2006-02-01

    Cis-N-[4-[4-(1,2-benzisozole-3-yl)-1-piperazinyl]butyl]cyclohexane-1,2-dicarboximide monohydrochloride dihydrate was studied spectroscopically. Complete NMR assignments were made using DEPT, H-H COSY, as well as HMQC and HMBC heteronuclear correlation techniques. The hydrochloride salt was found at delta > 10. The dihydrate was present in the region delta 3-4 in DMSO-d6 solvent. Asymmetry carbon C3 brought chemical-shift-nonequivalent of cis-cyclohexanyl group, splitting four systems H1, H1', H2 and H2'. Diamagnetic anisotropy of benzisozolyl group results in three troops peaks of piperazinyl group. PMID:16406787

  15. Synthesis, Preferentially Hypoxic Apoptosis and Anti-Angiogenic Activity of 3-Amino-1,2,4-Benzotriazine-1,4-Dioxide Bearing Alkyl Linkers with a 3-Amino-1,2,4-Benzotriazine-1-Oxide Moiety

    PubMed Central

    Lee, Chun-I; Huang, Chien-Ming; Huang, Wen-Hsin; Lee, An-Rong

    2014-01-01

    3-(Aminoalkylamino)-1,2,4-benzotriazine-1,4-dioxide-extended derivatives were synthesized by the structural modification of 3-amino-1,2,4-benzotriazine-1,4-dioxide (tirapazamine, TPZ) that incorporated homologue-alkyl linkers, without or with an extended 3-amino-1,2,4-benzotriazine-1-oxide moiety at the 3-position of the TPZ. According to sequential evaluation of preferentially normoxic and hypoxic cytotoxicities against MCF-7, NCI-H460 and HCT-116, most of the synthesized compounds exhibited hypoxic cytotoxicity greater than or comparable to that of TPZ. Among them, compounds 9a and 9b more powerfully inhibited the proliferation of MCF-7, NCI-H460 and HCT-116 in hypoxia than did TPZ. The representative of 3-(aminoalkylamino)-1,2,4-benzotriazine-1,4-dioxide-extended derivatives, 9a exhibited greater hypoxic cytotoxicity than TPZ, mediated by cell cycle arrest. The induction of DNA damage, the activation of caspase 3/7 and cleaved poly(ADP-ribose) polymerase-related apoptosis, which were detected in HCT-116 cells in both normoxia and hypoxia. In vitro anti-angiogenic assay of co-cultured HUVECs and fibroblasts that were exposed to the selected 7b, 8g, 9a and 9b exhibited 80-90% inhibition of tube formation at 20 μM, whereas TPZ exhibited approximately 50% inhibition of tube formation at 20 μM. At 2 μM, 9a and 9b significantly reduced the areas, lengths, paths and joints of tube formation by 70-80% and 45-50%, respectively. These results reveal that most of synthesized TPZ derivatives in this study exhibited more potent anti-angiogenesis than TPZ.

  16. 1-{(Z)-1-[3-(4-Bromo-phen-oxy)prop-oxy]-1-(2,4-difluoro-phen-yl)prop-1-en-2-yl}-1H-1,2,4-triazol-4-ium nitrate.

    PubMed

    Shen, Fei; Guo, Song; Luan, Yuan-Yuan; Wang, Kai; Hu, Yong-Hong

    2012-07-01

    In the title mol-ecular salt, C(20)H(19)BrF(2)N(3)O(2) (+)·NO(3) (-), the N atom at position 4 of the heterocyclic ring is protonated. The triazole ring makes dihedral angles of 96.6 (4) and 54.4 (3)° with the 4-bromo-phenyl and 2,4-difluoro-phenyl rings, respectively, and the mol-ecule adopts a Z conformation about the C=C double bond. In the crystal, cations and anions are linked by N-H⋯O and C-H⋯O hydrogen bonds. PMID:22807838

  17. 1,1'-Diethyl-4,4'-bipyridine-1,1'-diium bis(1,1,3,3-tetracyano-2-ethoxypropenide): multiple C-H...N hydrogen bonds form a complex sheet structure.

    PubMed

    Setifi, Zouaoui; Lehchili, Fouzia; Setifi, Fatima; Beghidja, Adel; Ng, Seik Weng; Glidewell, Christopher

    2014-03-01

    In the title salt, C14H18N2(2+) · 2C9H5N4O(-), the 1,1'-diethyl-4,4'-bipyridine-1,1'-diium dication lies across a centre of inversion in the space group P21/c. In the 1,1,3,3-tetracyano-2-ethoxypropenide anion, the two independent -C(CN)2 units are rotated, in conrotatory fashion, out of the plane of the central propenide unit, making dihedral angles with the central unit of 16.0(2) and 23.0(2)°. The ionic components are linked by C-H...N hydrogen bonds to form a complex sheet structure, within which each cation acts as a sixfold donor of hydrogen bonds and each anion acts as a threefold acceptor of hydrogen bonds. PMID:24594730

  18. Assimilatory Sulfate Reduction in C3, C3-C4, and C4 Species of Flaveria1

    PubMed Central

    Koprivova, Anna; Melzer, Michael; von Ballmoos, Peter; Mandel, Therese; Brunold, Christian; Kopriva, Stanislav

    2001-01-01

    The activity of the enzymes catalyzing the first two steps of sulfate assimilation, ATP sulfurylase and adenosine 5′-phosphosulfate reductase (APR), are confined to bundle sheath cells in several C4 monocot species. With the aim to analyze the molecular basis of this distribution and to determine whether it was a prerequisite or a consequence of the C4 photosynthetic mechanism, we compared the intercellular distribution of the activity and the mRNA of APR in C3, C3-C4, C4-like, and C4 species of the dicot genus Flaveria. Measurements of APR activity, mRNA level, and protein accumulation in six Flaveria species revealed that APR activity, cysteine, and glutathione levels were significantly higher in C4-like and C4 species than in C3 and C3-C4 species. ATP sulfurylase and APR mRNA were present at comparable levels in both mesophyll and bundle sheath cells of C4 species Flaveria trinervia. Immunogold electron microscopy demonstrated the presence of APR protein in chloroplasts of both cell types. These findings, taken together with results from the literature, show that the localization of assimilatory sulfate reduction in the bundle sheath cells is not ubiquitous among C4 plants and therefore is neither a prerequisite nor a consequence of C4 photosynthesis. PMID:11598228

  19. 40 CFR 721.1637 - 1,2-Propanediol, 3-(2-propenyloxy)-, bis(4-methylbenzene sulfonate); 2-propanol, 1-[2-[[(4...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1,2-Propanediol, 3-(2-propenyloxy)-, bis(4-methylbenzene sulfonate); 2-propanol, 1- oxy]ethoxy]-3-(2-propenyloxy)-4-methylbenzenesulfonate... Substances § 721.1637 1,2-Propanediol, 3-(2-propenyloxy)-, bis(4-methylbenzene sulfonate); 2-propanol, 1-...

  20. 40 CFR 721.1637 - 1,2-Propanediol, 3-(2-propenyloxy)-, bis(4-methylbenzene sulfonate); 2-propanol, 1-[2-[[(4...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 1,2-Propanediol, 3-(2-propenyloxy)-, bis(4-methylbenzene sulfonate); 2-propanol, 1- oxy]ethoxy]-3-(2-propenyloxy)-4-methylbenzenesulfonate... Substances § 721.1637 1,2-Propanediol, 3-(2-propenyloxy)-, bis(4-methylbenzene sulfonate); 2-propanol, 1-...

  1. Crystal structure of 2-(1,3-dioxoindan-2-yl)iso­quinoline-1,3,4-trione

    PubMed Central

    Ghalib, Raza Murad; Chidan Kumar, C. S.; Hashim, Rokiah; Sulaiman, Othman; Fun, Hoong-Kun

    2015-01-01

    In the title iso­quinoline-1,3,4-trione derivative, C18H9NO5, the five-membered ring of the indane fragment adopts an envelope conformation with the nitro­gen-substituted C atom being the flap. The planes of the indane benzene ring and the iso­quinoline-1,3,4-trione ring make a dihedral angle of 82.06 (6)°. In the crystal, mol­ecules are linked into chains extending along the bc plane via C—H⋯O hydrogen-bonding inter­actions, enclosing R 2 2(8) and R 2 2(10) loops. The chains are further connected by π–π stacking inter­ations, with centroid-to-centroid distances of 3.9050 (7) Å, forming layers parallel to the b axis. PMID:25705509

  2. Crystal structure of 2-ethyl-4-methyl-1-(2-oxido-3,4-dioxo-cyclo-but-1-en-1-yl)-1H-imidazol-3-ium.

    PubMed

    Korkmaz, Ufuk; Bulut, Iclal; Bulut, Ahmet

    2016-07-01

    In the title inner salt molecule, C10H10N2O3, the four-membered cyclobutene ring is twisted by 7.1 (2)° with respect to the five-membered imidazole ring. The crystal packing exhibits an R 2 (2)(9) hydrogen-bonding ring motif through N-H⋯O and C-H⋯O inter-actions. The potential non-linear optical properties were studied by a computational ab initio calculations performed at the DFT/B3LYP/6-31++G(d,p) level of theory. PMID:27555949

  3. Nucleosides of 4-methylthio-1,2,3-triazol-5-yl-carboxylic acid derivatives

    SciTech Connect

    Shingarova, I.D.; Yartseva, I.V.; Preobrazhenskaya, M.N.

    1987-08-01

    2-..beta..-D-Ribofuranosyl-4-methylthio-5-methoxycarbonyl-1,2,3-triazole was obtained by fusing 4-methylthio-5-methoxycarbonyl-1,2,3-triazole together with tetraacyl-D-ribofuranose, followed by deacylation, and its amide and hydrazide were prepared. The structures of the new nucleosides were established by converting them into known 2-nucleosides of 1,2,3-triazol-4-yl-carboxylic acid derivatives. By comparing PMR spectra with previously reported PMR spectra for the isomeric 1- and 2-nucleosides of 1,2,3-triazol-4-yl-carboxylic acid derivatives, the synthesized nucleosides could be assigned to 2-substituted triazoles.

  4. Exendin-4 induces myocardial protection through MKK3 and Akt-1 in infarcted hearts.

    PubMed

    Du, Jianfeng; Zhang, Ling; Wang, Zhengke; Yano, Naohiro; Zhao, Yu Tina; Wei, Lei; Dubielecka-Szczerba, Patrycja; Liu, Paul Y; Zhuang, Shougang; Qin, Gangjian; Zhao, Ting C

    2016-02-15

    We have demonstrated that glucagon like peptide-1 (GLP-1) protects the heart against ischemic injury. However, the physiological mechanism by which GLP-1 receptor (GLP-1R) initiates cardioprotection remains to be determined. The objective of this study is to elucidate the functional roles of MAPK kinase 3 (MKK3) and Akt-1 in mediating exendin-4-elicited protection in the infarcted hearts. Adult mouse myocardial infarction (MI) was created by ligation of the left descending artery. Wild-type, MKK3(-/-), Akt-1(-/-), and Akt-1(-/-);MKK3(-/-) mice were divided into one of several groups: 1) sham: animals underwent thoracotomy without ligation; 2) MI: animals underwent MI and received a daily dose of intraperitoneal injection of vehicle (saline); 3) MI + exendin-4: infarcted mice received daily injections of exendin-4, a GLP-1R agonist (0.1 mg/kg, ip). Echocardiographic measurements indicate that exendin-4 treatment resulted in the preservation of ventricular function and increases in the survival rate, but these effects were diminished in MKK3(-/-), Akt-1(-/-), and Akt-1(-/-);MKK3(-/-) mice. Exendin-4 treatments suppressed cardiac hypotrophy and reduced scar size and cardiac interstitial fibrosis, respectively, but these beneficial effects were lost in genetic elimination of MKK3, Akt-1, or Akt-1(-/-);MKK3(-/-) mice. GLP-1R stimulation stimulated angiogenic responses, which were also mitigated by deletion of MKK3 and Akt-1. Exendin-4 treatment increased phosphorylation of MKK3, p38, and Akt-1 at Ser129 but decreased levels of active caspase-3 and cleaved poly (ADP-ribose) polymerase; these proteins were diminished in MKK3(-/-), Akt-1(-/-), and Akt-1(-/-);MKK3(-/-) mice. These results reveal that exendin-4 treatment improves cardiac function, attenuates cardiac remodeling, and promotes angiogenesis in the infarcted myocardium through MKK3 and Akt-1 pathway. PMID:26739490

  5. 3-(4-Bromo-benzyl-idene)-1,5-dioxaspiro-[5.5]undecane-2,4-dione.

    PubMed

    Zeng, Wu-Lan

    2011-01-01

    The title mol-ecule, C(16)H(15)BrO(4), was prepared by the reaction of (R)-2,4-dioxo-1,5-dioxaspiro-[5.5]undecane and 4-bromo-benzaldehyde with ethanol. The 1,3-dioxane ring exhibits a distorted boat and the fused cyclo-hexane ring exhibits a chair conformation. PMID:21523094

  6. 49 CFR 173.124 - Class 4, Divisions 4.1, 4.2 and 4.3-Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... § 173.124, see the List of CFR Sections Affected, which appears in the Finding Aids section of the... exothermic decomposition even without participation of oxygen (air). A material is excluded from this...: (1) Its heat of decomposition is less than 300 J/g; or (2) Its self-accelerating...

  7. 4-{4-[(4-Oxoquinazolin-3-yl)meth­yl]-1H-1,2,3-triazol-1-yl}butyl acetate

    PubMed Central

    Ouahrouch, Abdelaaziz; Taourirte, Moha; Lazrek, Hassan B.; El Azhari, Mohamed; Saadi, Mohamed; El Ammari, Lahcen

    2011-01-01

    In the heterocyclic title compound, C17H19N5O3, the quinazolinone ring system forms a dihedral angle of 67.22 (7)° with the triazole ring. The butyl acetate group has a non-linear conformation, with an alternation of synclinal and anti­periplanar torsion angles [N—C—C—C = 58.5 (2)°, C—C—C—C = 170.72 (19)° and C—C—C—O = −65.9 (3)°]. The crystal structure features inter­molecular C—H⋯N and C—H⋯O non-classical hydrogen bonds, building an infinite one-dimensional network along the [100] direction. PMID:22199711

  8. Interactions of arabinoxylan and (1,3)(1,4)-β-glucan with cellulose networks.

    PubMed

    Mikkelsen, Deirdre; Flanagan, Bernadine M; Wilson, Sarah M; Bacic, Antony; Gidley, Michael J

    2015-04-13

    To identify interactions of relevance to the structure and properties of the primary cell walls of cereals and grasses, we used arabinoxylan and (1,3)(1,4)-β-glucan, major polymers in cereal/grass primary cell walls, to construct composites with cellulose produced by Gluconacetobacter xylinus. Both polymers associated prolifically with cellulose without becoming rigid or altering the nature or extent of cellulose crystallinity. Mechanical properties were modestly affected compared with xyloglucan or pectin (characteristic components of nongrass primary cell walls) composites with cellulose. In situ depletion of arabinoxylan arabinose side chains within preformed cellulose composites resulted in phase separation, with only limited enhancement of xylan-cellulose interactions. These results suggest that arabinoxylan and (13)(14)-β-d-glucan are not functional homologues for either xyloglucan or pectin in the way they interact with cellulose networks. Association of cell-wall polymers with cellulose driven by entropic amelioration of high energy cellulose/water interfaces should be considered as a third type of interaction within cellulose-based cell walls, in addition to molecular binding (enthalpic driving force) exhibited by, for example, xyloglucans or mannans, and interpenetrating networks based on, for example, pectins. PMID:25756836

  9. Comparison crystal structure conformations of two structurally related biphenyl analogues: 4,4′-bis­[3-(pyrrolidin-1-yl)prop-1-yn-1-yl]-1,1′-biphenyl and 4,4′-bis­{3-[(S)-2-methyl­pyrrolidin-1-yl]prop-1-yn-1-yl}-1,1′-biphen­yl

    PubMed Central

    Wan, Anqi; Penthala, Narsimha Reddy; Fifer, E. Kim; Parkin, Sean; Crooks, Peter A.

    2015-01-01

    The title compounds, C26H28N2, (I), and C28H32N2, (II), were designed based on the structure of the potent α9α10 nicotinic acetyl­choline receptor antagonist ZZ161C {1,1′-[[1,1′-biphen­yl]-4,4′-diylbis(prop-2-yne-3,1-di­yl)]bis­(3,4-di­methyl­pyridin-1-ium) bromide}. In order to improve the druglikeness properties of ZZ161C for potential oral administration, the title compounds (I) and (II) were prepared by coupling 4,4′-bis­(3-bromo­prop-1-yn-1-yl)-1,1′-biphenyl with pyrrol­idine, (I), and (S)-2-methyl­pyrrolidine, (II), respectively, in aceto­nitrile at room temperature. The asymmetric unit of (I) contains two half mol­ecules that each sit on sites of crystallographic inversion. As a result, the biphenyl ring systems in compound (I) are coplanar. The biphenyl ring system in compound (II), however, has a dihedral angle of 28.76 (11)°. In (I), the two independent mol­ecules differ in the orientation of the pyrrolidine ring (the nitro­gen lone pair points towards the biphenyl rings in one mol­ecule, but away from the rings in the other). The torsion angles about the ethynyl groups between the planes of the phenyl rings and the pyrrolidine ring N atoms are 84.15 (10) and −152.89 (10)°. In compound (II), the corresponding torsion angles are 122.0 (3) and 167.0 (3)°, with the nitro­gen lone pairs at both ends of the mol­ecule directed away from the central biphenyl rings. PMID:26594393

  10. 40 CFR 721.8940 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Chromate(3-), bis phenyl]sulfonyl... Specific Chemical Substances § 721.8940 Chromate(3-), bis phenyl]sulfonyl] amino]-4-(oxo-.kappa.O)-5... substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  11. 40 CFR 721.8940 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Chromate(3-), bis phenyl]sulfonyl... Specific Chemical Substances § 721.8940 Chromate(3-), bis phenyl]sulfonyl] amino]-4-(oxo-.kappa.O)-5... substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  12. 40 CFR 721.8940 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Chromate(3-), bis phenyl]sulfonyl... Specific Chemical Substances § 721.8940 Chromate(3-), bis phenyl]sulfonyl] amino]-4-(oxo-.kappa.O)-5... substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  13. Pyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazines as Selective, Brain Penetrant Phosphodiesterase 2 (PDE2) Inhibitors

    PubMed Central

    2015-01-01

    A novel series of pyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazines is reported as potent PDE2/PDE10 inhibitors with drug-like properties. Selectivity for PDE2 was obtained by introducing a linear, lipophilic moiety on the meta-position of the phenyl ring pending from the triazole. The SAR and protein flexibility were explored with free energy perturbation calculations. Rat pharmacokinetic data and in vivo receptor occupancy data are given for two representative compounds 6 and 12. PMID:25815146

  14. Pyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazines as Selective, Brain Penetrant Phosphodiesterase 2 (PDE2) Inhibitors.

    PubMed

    Rombouts, Frederik J R; Tresadern, Gary; Buijnsters, Peter; Langlois, Xavier; Tovar, Fulgencio; Steinbrecher, Thomas B; Vanhoof, Greet; Somers, Marijke; Andrés, José-Ignacio; Trabanco, Andrés A

    2015-03-12

    A novel series of pyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazines is reported as potent PDE2/PDE10 inhibitors with drug-like properties. Selectivity for PDE2 was obtained by introducing a linear, lipophilic moiety on the meta-position of the phenyl ring pending from the triazole. The SAR and protein flexibility were explored with free energy perturbation calculations. Rat pharmacokinetic data and in vivo receptor occupancy data are given for two representative compounds 6 and 12. PMID:25815146

  15. Crystal structures of three substituted 3-aryl-2-phenyl-2,3-di-hydro-4H-1,3-benzo-thia-zin-4-ones.

    PubMed

    Yennawar, Hemant P; Coyle, David J; Noble, Duncan J; Yang, Ziwei; Silverberg, Lee J

    2016-08-01

    Three ring-substituted 3-aryl analogs of 2-phenyl-2,3-di-hydro-4H-1,3-benzo-thia-zin-4-one, namely 3-(4-meth-oxy-phen-yl)-2-phenyl-4H-1,3-benzo-thia-zin-4-one, C21H17NO2S, (I), 2-phenyl-3-[4-(tri-fluoro-meth-yl)phen-yl]-2,3-di-hydro-4H-1,3-benzo-thia-zin-4-one toluene hemisolvate, C21H14F3NOS·0.5C7H8, (II), and 3-(3-bromo-phen-yl)-2-phenyl-2,3-di-hydro-4H-1,3-benzo-thia-zin-4-one toluene hemisolvate, C20H14BrNOS·0.5C7H8, (III), were synthesized and their crystal structures determined. The hemisolvates differ in that in (II), the asymmetric unit comprises two molecules of the benzo-thia-zinone compound and a toluene solvent mol-ecule, whereas in (III), the unit comprises one benzo-thia-zinone mol-ecule and a half-occupancy toluene solvent mol-ecule. All crystals are of racemic mixtures of the chiral 2-C atom of the thia-zine moiety, which in all structures has a screw-boat puckering, with the puckering amplitude values within the range 0.575-0.603 Å. In all three structures, the benzene plane of the benzo-thia-zine system makes a dihedral angle in the range 78.60 (5) to 98.40 (5)° with the unsubstituted benzene plane and in the range 70.50 (1) to 121.00 (5)° with the substituted benzene plane. The CF3 substituent group in one of the mol-ecules of (II) shows positional disorder, with an occupancy ratio of 0.57 (3):0.43 (3). In the crystals of (I) and (II), weak inter-molecular C-H⋯O inter-actions are present, giving in (I), mol-ecules arranged in a plane parallel to (010), and in (II), chains along a. In addition, all three structures show weak C-H⋯π inter-actions involving various aromatic rings. PMID:27536392

  16. ERIC/CRESS News Letter, Volume 4, Nos. 1, 2, 3, & 4, 1969.

    ERIC Educational Resources Information Center

    ERIC Clearinghouse on Rural Education and Small Schools, Las Cruces, NM.

    Included in this publication are the 4 issues of the ERIC/CRESS (Educational Research Information Center/Clearinghouse on Rural Education and Small Schools) newsletter published during 1969. Articles in issue Number 1 include: "Office of Education Summer Training Institutes"; "Migrant Education Conference"; "The Principalship-Fellowship…

  17. Preparation and properties of polyformals obtained from 2,2-bis(4-hydroxyphenyl)-1,1,1,3,3,3,-hexafluoropropane and dichloromethane

    SciTech Connect

    Nakamura, S.; Suzuki, Y.; Tamura, E.; Kuriki, M.; Saegusa, Y.

    1993-12-31

    Fluorine-containing aromatic polyformal and copolyformals were prepared from 2,2-bis(4-hydroxyphenyl)-1,1,1,3,3,3,-hexafluoropropane (bis-phenol AF) and/or 2,2-bis(4-hydroxyphenyl)-propane (bisphenol A) with dichloromethane. High molecular-weight polyformal and copolyformals were obtained by using NMP as solvent and in the presence of KOH. The thermal stability was lowered with increasing fluorine content. The Tg increased monotonically with fluorine content from 89{degrees}C for bisphenol A polyformal to 17{degrees}C for bisphenol AF polyformal. Bisphenol a polyformal was soluble in limited solvents, whereas bisphenol AF polyformal was soluble in a wide variety of solvents such aprotic polar solvents, aromatic solvents and chlorinated hydrocarbons.

  18. Preparation of 3-substituted-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines as RET kinase inhibitors.

    PubMed

    Dinér, Peter; Alao, John P; Söderlund, Johan; Sunnerhagen, Per; Grøtli, Morten

    2012-05-24

    A series of 3-substituted-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines have been designed, synthesized, and evaluated as RET protein kinase inhibitors. On the basis of docking results, a small library of pyrazolopyrimidine compounds with an extended hydrophobic side arm was synthesized. The most promising of the compounds (7a) displayed efficient inhibition in vitro and good selectivity when tested on a panel of kinases. Furthermore, 7a inhibited GDNF-induced RET phosphorylation of ERK1/2 in MCF-7 breast cancer cells at concentrations as low as 100 nM. PMID:22559926

  19. (2E)-1-[5-Methyl-1-(4-methyl­phen­yl)-1H-1,2,3-triazol-4-yl]-3-[4-(piperidin-1-yl)phen­yl]prop-2-en-1-one1

    PubMed Central

    Abdel-Wahab, Bakr F.; Abdel-Latif, Ehab; Ng, Seik Weng; Tiekink, Edward R. T.

    2013-01-01

    Two independent mol­ecules comprise the asymmetric unit of the title compound, C24H26N4O. The major difference between them is found in the relative orientation of the triazole-bound p-tolyl group which have the opposite sense of twist [N—N—C—C torsion angles = 55.8 (3) and −49.8 (3)°]. The chalcone residue is almost coplanar with the triazole ring [N—C—C—O and C—C—C—C torsion angles = −178.9 (2) and −178.5 (2)°, respectively; cf. 177.9 (3) and 168.5 (3)°, respectively, in the second mol­ecule]. The conformation about each C=C double bond is E and in each case the triazole methyl group is syn to the carbonyl O atom. In the crystal, mol­ecules aggregate into layers parallel to (-113). The first independent mol­ecule self-associates into a layer via C—H⋯O and C—H⋯π inter­actions. By contrast, layers comprising the second independent mol­ecule do not feature specific inter­actions between mol­ecules. The global crystal packing comprises alternating layers. PMID:23723806

  20. Synthesis and pharmacological properties of 1-[2-hydroxy-3-(4-o,m,p-halogenophenyl)- and 3-(4-m-chlorophenyl)-1-piperazinyl]propyl derivatives of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d]pyrimidine-5-carboxylic acid with analgesic and sedative activities.

    PubMed

    Sabiniarz, Aleksandra; Sladowska, Helena; Filipek, Barbara; Sapa, Jacek; Dudek, Magdalena; Slepokura, Katarzyna

    2007-01-01

    Synthesis of 1-[2-hydroxy-3-(4-o,m,p-halogenophenyl)- and 3-(4-m-chlorophenyl)-1-piperazinyl]propyl derivatives of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acid (18, 20-23, 25, 27-30 and 19, 24, 26) is described. All substances were active as analgesic agents in "writhing syndrome" test and except of 18 and 23 they acted stronger than acetylsalicylic acid. All final derivatives tested significantly suppressed the spontaneous locomotor activity of mice. PMID:18536164

  1. Spin liquid state in the S=1 vanadium kagome YCa3(VO)3(BO3)4

    NASA Astrophysics Data System (ADS)

    Wiebe, Christopher; Silverstein, Harlyn; Gardner, Jason; Zhou, Haidong

    2015-03-01

    Over the last decade, the search for model kagome compounds has been fruitful for S=1/2 Cu2+ spins in the minerals Herbertsmithite and Volborthite. There are fewer comparable materials for S=1 analogues, but recent progress has been made with the discovery of YCa3(VO)3(BO3)4, which has a network of V3+ kagome spins. Previous reports were made of no magnetic ordering down to 1.5 K in this compound, despite strong antiferromagnetic exchange. Here we report a new synthesis method for this material which reduces impurity levels, resulting in high quality polycrystalline samples of YCa3(VO)3(BO3)4. Neutron scattering experiments show no evidence for long-ranged magnetic ordering down to 50 mK, with gapped inelastic excitations developing similar to S=1/2 kagome compounds. Heat capacity and susceptibility measurements also show a lack of long-range magnetic order and a lack of spin glassiness, placing this compound as a new spin liquid candidate.

  2. 26 CFR 1.4-3 - Husband and wife filing separate returns.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Husband and wife filing separate returns. 1.4-3... TAXES Normal Taxes and Surtaxes § 1.4-3 Husband and wife filing separate returns. (a) In general. If the separate adjusted gross income of a husband is less than $5,000 and the separate adjusted gross income...

  3. 26 CFR 1.702-3T - 4-Year spread (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false 4-Year spread (temporary). 1.702-3T Section 1... (CONTINUED) INCOME TAXES Partners and Partnerships § 1.702-3T 4-Year spread (temporary). (a) Applicability... spread. A partner may elect out of the rules of paragraph (b) of this section by meeting the...

  4. 26 CFR 1.702-3T - 4-Year spread (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false 4-Year spread (temporary). 1.702-3T Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Partners and Partnerships § 1.702-3T 4-Year spread (temporary). (a... taxable year for the first taxable year beginning after December 31, 1986 (partnership's year of...

  5. 2-(4-Chloro-3-nitro­phen­yl)-4-(4-chloro­phen­yl)-1,3-thia­zole

    PubMed Central

    Nayak, Susanta K.; Venugopala, K. N.; Chopra, Deepak; Govender, Thavendran; Kruger, Hendrik G.; Maguire, Glenn E. M.; Guru Row, T. N.

    2009-01-01

    The title compound, C15H8Cl2N2O2S, crystallizes with two mol­ecules in the asymmetric unit. The dihedral angles between the 4-chloro-3-nitro­phenyl ring and the thia­zole ring are 0.5 (1) and 7.1 (1)° and those between the 4-chloro­phenyl ring and the thia­zole ring are 7.1 (1) and 7.4 (1)° in the two mol­ecules. The crystal structure is stabilized by inter­molecular C—H⋯Cl and C—H⋯O hydrogen bonds. PMID:21578228

  6. Synthesis and Anticonvulsant Activity Evaluation of 3-alkoxy-4-(4-(hexyloxy/heptyloxy)phenyl)-4H-1,2,4 -triazole

    PubMed Central

    Fang, Ying-Quan; Sun, Chun-Ling; Liu, Da-Chuan; Wang, Shi-Ben; Quan, Zhe-San

    2015-01-01

    A series of 3-alkoxy-4-(4-(hexyloxy/heptyloxy) phenyl)-4H-1,2,4-triazole was synthesized. The anticonvulsant effect and neurotoxicity of the compounds were calculated with maximal electroshock (MES) test and rotarod tests with intraperitoneally injected mice. Among the synthesized compounds, compound 3-heptyloxy-4-(4-(hexyloxy) phenyl)-4H-1,2,4-triazole (5f) was the most active one and also had the lowest toxicity. In the anti-MES potency test, it showed median effective dose (ED50) of 37.3 mg/Kg, median toxicity dose (TD50) of 422.5 mg/Kg, and the protective index (PI) of 11.3 which is much greater than the reference drug carbamazepine with PI value of 6.4. As well as demonstrating the anti-MES efficacy of compound 5f, its potency against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline were also established, with the results suggesting that GABA-mediated mechanisms might be involved in its anticonvulsant activity, such as enhancing of GABAergic neurotransmission or activity, activate GAD or inhibit GABA-T, and GABAA-mediated mechanisms. PMID:25561914

  7. Vicarious nucleophilic substitution using 4-amino-1,2,4-triazole, hydroxylamine or O-alkylhydroxylamine to prepare 1,3-diamino-2,4,6-trinitrobenzene or 1,3,5-triamino-2,4,6-trinitrobenzene

    DOEpatents

    Mitchell, Alexander R.; Pagoria, Philip F.; Schmidt, Robert D.

    1997-01-01

    The present invention relates to a process to produce 1,3-diamino-2,4,6-trinitrobenzene (DATB) or 1,3,5-triamino-2,4,6,-trinitrobenzene (TATB) by: (a) reacting at ambient pressure and a temperature of between about 0.degree. and 50.degree. C. for between about 0.1 and 24 hr, a trinitroaromatic compound of structure V: ##STR1## wherein X, Y, and Z are each independently selected from the group consisting of --H and --NH.sub.2, with the proviso that at least 1 or 2 of X, Y, and Z are hydrogen; with an effective amount of 1-amino-1,2,4-triazole, hydroxylamine or O-alkylhydroxamine to produce DATB or TATB; in the presence of a strong base selected from sodium butoxide, potassium butoxide, potassium propoxide, sodium propoxide, sodium ethoxide, potassium ethoxide, sodium methoxide, potassium methoxide, and combinations thereof; in a solvent selected from the group consisting of methanol, ethanol, propanol, butanol, dimethylsulphoxide, N-methylpyrrolidone, hexamethylphosphoramide, dimethylformide, dimethylacetamide and mixtures thereof, provided that when alcohols are present or when hydroxylamine or its O-alkyl derivatives replace ATA primarily DATB is formed; and (b) isolating the DATB or TATB produced. DATB and TATB are important and useful specialty explosives and intermediates for other materials.

  8. Synthesis and structure of spiro[2-(2-methylphenyl)-4 H-1,3-benzoxazine-4,2'-adamantane

    NASA Astrophysics Data System (ADS)

    Osyanin, V. A.; Ivleva, E. A.; Rybakov, V. B.; Klimochkin, Yu. N.

    2015-01-01

    Synthesis and an X-ray diffraction study of spiro[2-(2-methylphenyl)-4 H-1,3-benzoxazine-4,2'-adamantane] C24H25NO are performed: monoclinic crystal system, space group P21/ c, a = 13.9424(3) Å, b = 7.56554(17) Å, c = 17.0155(3) Å, β = 99.6457(18)°, Z = 4, V = 1769.45(6) Å3. ρcalcd = 1.244 g/cm3, R = 0.0339 [ T = 100(2) K]. The oxazine ring of the molecule adopts the boat conformation. The bond lengths and angles are standard for this class of compounds.

  9. Synthesis and properties of new derivatives of ethyl 7-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d]pyrimidine-5-carboxylate.

    PubMed

    Sladowska, H; Bartoszko-Malik, A; Zawisza, T

    1990-01-01

    Condensation of diethyl 2-amino-6-methylpyridine-3,4-dicarboxylate with phenyl or cyclohexyl isocyanates gave the corresponding derivatives of ethyl 7-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d]pyrimidine- 5-carboxylate[(V), (VI)]. Alkylation of (V) and (VI) afforded the corresponding N-1 substituted derivatives (XI-XIX). PMID:2337441

  10. Difurazano[3,4-b:3',4'-f]-4,5-diaza-1,8-dioxacyclododecine and an acyclic analogue.

    PubMed

    Averkiev, Boris B; Timofeeva, Tatiana V; Sheremetev, Aleksey B; Shatunova, Elena V; Antipin, Mikhail Yu

    2004-07-01

    The novel title furazan-containing macrocycle (systematic name: 6,9,14,17-tetraoxa-2,3,5,7,16,18-hexaazatricyclo[13.3.0.0(4,8)]octadeca-4,7,15,18-tetraene), C8H10N6O4, (I), is the first macrocycle where the furazan rings are connected via a hydrazine group. In spite of the strain in the 12-membered macrocycle of (I), the geometry of the furazan fragment is the same in (I) and in its acyclic analogue 1,8-bis(5-aminofurazan-4-yloxy)-3,6-dioxaoctane, C10H16N6O6, (II). In both compounds, the participation of the furazan rings in intermolecular hydrogen bonding equalizes the N-O bonds within the furazan rings, in contrast with rings which do not participate in such interactions. PMID:15237185

  11. Cd(II) complexes with different nuclearity and dimensionality based on 3-hydrazino-4-amino-1,2,4-triazole

    SciTech Connect

    Xu, Cai-Xia; Zhang, Jian-Guo Yin, Xin; Jin, Xin; Li, Tong; Zhang, Tong-Lai; Zhou, Zun-Ning

    2015-03-15

    A series of zero- to two-dimensional Cd(II) coordination compounds have been synthesized by the reaction of Cd(II) salts and 3-hydrazino-4-amino-1,2,4-triazole di-hydrochloride (HATr·2HCl). [CdCl{sub 2}(HATr){sub 2}] (1) and [Cd{sub 2}Cl{sub 4}(HATr){sub 2}(H{sub 2}O){sub 2}] (2) have discrete mononuclear and binuclear structures, respectively. [Cd(HATr){sub 2}(ClO{sub 4}){sub 2}]{sub n} (3) presents polymeric 1-D chain and [Cd{sub 2}(NO{sub 3}){sub 2}Cl{sub 2}(HATr){sub 2}]{sub n} (4) shows 2-D frameworks. All Cd(II) ions exhibit distorted octahedral configurations in 13, whilst both hexa and heptacoordinated Cd(II) are formed in 4. The HATr ligands adopt chelating coordinated mode in 1, while tri-dentate bridging–chelating mode in 2–4. The chloride ion is a mono-coordinated ligand in 1 and 2, but it bridges two adjacent metal ions in 4. Furthermore, thermal behaviors have been investigated and the results reveal that all complexes have good thermal stability. The impact sensitivity test indicates that complex 3 is sensitive to impact stimuli. - Graphical abstract: Four Cd(II) complexes based on 3-hydrazino-4-amino-1,2,4-triazole ligands exhibit diverse structures from mononuclear to 2D networks. - Highlights: • Cd(II) complexes containing 3-hydrazino-4-amino-1,2,4-triazole ligands. • Mononuclear, binuclear, 1-D and 2-D structures. • Good thermal stability. • Thermal decomposition kinetics.

  12. 40 CFR 721.7280 - 1,3-Propanediamine, N,N′-1,2-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl...-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl-4..., reaction products with N-butyl-2,2,6,6-tetramethyl-4-piperidinamine (PMN P-89-632) is subject to...

  13. 40 CFR 721.7280 - 1,3-Propanediamine, N,N′-1,2-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl...-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl-4..., reaction products with N-butyl-2,2,6,6-tetramethyl-4-piperidinamine (PMN P-89-632) is subject to...

  14. 40 CFR 721.7280 - 1,3-Propanediamine, N,N′-1,2-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl...-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl-4..., reaction products with N-butyl-2,2,6,6-tetramethyl-4-piperidinamine (PMN P-89-632) is subject to...

  15. 40 CFR 721.7280 - 1,3-Propanediamine, N,N′-1,2-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl...-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl-4..., reaction products with N-butyl-2,2,6,6-tetramethyl-4-piperidinamine (PMN P-89-632) is subject to...

  16. Asymmetric synthesis of bicyclo[4.3.1]decadienes and bicyclo[3.3.2]decadienes via [6 + 3] trimethylenemethane cycloaddition with tropones.

    PubMed

    Trost, Barry M; McDougall, Patrick J; Hartmann, Olaf; Wathen, Peter T

    2008-11-12

    The cyanosubstituted trimethylenemethane donor undergoes palladium-catalyzed [6 + 3] cycloaddition with a variety of tropones to yield bicyclo[4.3.1]decadienes in excellent regio-, diastereo-, and enantioselectivity. Products of the Pd-TMM [6 + 3] cycloaddition participate in a thermal [3,3] sigmatropic rearrangement to yield bicyclo[3.3.2]decadienes in good yield. PMID:18937462

  17. Syntheses and biological evaluation of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib.

    PubMed

    Li, Yong-Tao; Wang, Jing-Han; Pan, Cheng-Wen; Meng, Fan-Fei; Chu, Xiao-Qian; Ding, Ya-hui; Qu, Wen-Zheng; Li, Hui-ying; Yang, Cheng; Zhang, Quan; Bai, Cui-Gai; Chen, Yue

    2016-03-01

    Three novel series of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib were prepared and evaluated in vitro for their cytostatic effects against a human chronic myeloid leukemia (K562), acute myeloid leukemia (HL60), and human leukemia stem-like cell line (KG1a). The structure-activity relationship was analyzed by determining the inhibitory rate of each imatinib analog. Benzene and piperazine rings were necessary groups in these compounds for maintaining inhibitory activities against the K562 and HL60 cell lines. Introducing a trifluoromethyl group significantly enhanced the potency of the compounds against these two cell lines. Surprisingly, some compounds showed significant inhibitory activities against KG1a cells without inhibiting common leukemia cell lines (K562 and HL60). These findings suggest that these compounds are able to inhibit leukemia stem-like cells. PMID:26850004

  18. A role for 3-O-sulfotransferase isoform-4 in assisting HSV-1 entry and spread

    SciTech Connect

    Tiwari, Vaibhav; O'Donnell, Christopher D.; Oh, Myung-Jin; Valyi-Nagy, Tibor; Shukla, Deepak . E-mail: dshukla@uic.edu

    2005-12-16

    Many heparan sulfate (HS) 3-O-sulfotransferase (3-OST) isoforms generate cellular receptors for herpes simplex virus type-1 (HSV-1) glycoprotein D (gD). Interestingly, the ability of 3-OST-4 to mediate HSV-1 entry and cell-to-cell fusion has not been determined, although it is predominantly expressed in the brain, a primary target of HSV-1 infections. We report that expression of 3-OST-4 can render Chinese hamster ovary K1 (CHO-K1) cells susceptible to entry of wild-type and a mutant (Rid1) strain of HSV-1. Evidence for generation of gD receptors by 3-OST-4 was suggested by gD-mediated interference assay and the ability of 3-OST-4 expressing CHO-K1 cells to preferentially bind HSV-1 gD, which could be reversed by prior treatment of cells with HS lyases (heparinases-II/III). In addition, 3-OST-4 expressing CHO-K1 cells acquired the ability to fuse with cells-expressing HSV-1 glycoproteins. Demonstrating specificity, the cell fusion was inhibited by soluble 3-O-sulfated forms of HS, but not unmodified HS. Taken together our results suggest a role of 3-OST-4 in HSV-1 pathogenesis.

  19. Vicarious nucleophilic substitution using 4-amino-1,2,4-triazole, hydroxylamine or O-alkylhydroxylamine to prepare 1,3-diamino-2,4,6-trinitrobenzene or 1,3,5-triamino-2,4,6-trinitrobenzene

    DOEpatents

    Mitchell, A.R.; Pagoria, P.F.; Schmidt, R.D.

    1997-05-27

    The present invention relates to a process to produce 1,3-diamino-2,4,6-trinitrobenzene (DATB) or 1,3,5-triamino-2,4,6,trinitrobenzene (TATB) by: (a) reacting at ambient pressure and a temperature of between about 0 and 50 C for between about 0.1 and 24 hr, a trinitroaromatic compound of the structure shown where X, Y, and Z are each independently selected from the group consisting of -H and -NH{sub 2}, with the proviso that at least 1 or 2 of X, Y, and Z are hydrogen; with an effective amount of 1-amino-1,2,4-triazole, hydroxylamine or O-alkylhydroxamine to produce DATB or TATB; in the presence of a strong base selected from sodium butoxide, potassium butoxide, potassium propoxide, sodium propoxide, sodium ethoxide, potassium ethoxide, sodium methoxide, potassium methoxide, and combinations thereof; in a solvent selected from the group consisting of methanol, ethanol, propanol, butanol, dimethylsulphoxide, N-methylpyrrolidone, hexamethylphosphoramide, dimethylformide, dimethylacetamide and mixtures thereof, provided that when alcohols are present or when hydroxylamine or its O-alkyl derivatives replace ATA primarily DATB is formed; and (b) isolating the DATB or TATB produced. DATB and TATB are important and useful specialty explosives and intermediates for other materials.

  20. Hydrogenous Zintl phase Ba3Si4Hx (x = 1-2): transforming Si4 "butterfly" anions into tetrahedral moieties.

    PubMed

    Kranak, Verina F; Benson, Daryn E; Wollmann, Lukas; Mesgar, Milad; Shafeie, Samrand; Grins, Jekabs; Häussermann, Ulrich

    2015-02-01

    The hydride Ba(3)Si(4)H(x) (x = 1-2) was prepared by sintering the Zintl phase Ba(3)Si(4), which contains Si(4)(6-) butterfly-shaped polyanions, in a hydrogen atmosphere at pressures of 10-20 bar and temperatures of around 300 °C. Initial structural analysis using powder neutron and X-ray diffraction data suggested that Ba(3)Si(4)H(x) adopts the Ba(3)Ge(4)C(2) type [space group I4/mcm (No. 140), a ≈ 8.44 Å, c ≈ 11.95 Å, Z = 8] where Ba atoms form a three-dimensional array of corner-condensed octahedra, which are centered by H atoms. Tetrahedron-shaped Si(4) polyanions complete a perovskite-like arrangement. Thus, hydride formation is accompanied by oxidation of the butterfly polyanion, but the model with the composition Ba(3)Si(4)H is not charge-balanced. First-principles computations revealed an alternative structural scenario for Ba(3)Si(4)H(x), which is based on filling pyramidal Ba5 interstices in Ba(3)Si(4). The limiting composition is x = 2 [space group P4(2)/mmm (No. 136), a ≈ 8.4066 Å, c ≈ 12.9186 Å, Z = 8], and for x > 1, Si atoms also adopt tetrahedron-shaped polyanions. Transmission electron microscopy investigations showed that Ba(3)Si(4)H(x) is heavily disordered in the c direction. Most plausible is to assume that Ba(3)Si(4)H(x) has a variable H content (x = 1-2) and corresponds to a random intergrowth of P- and I-type structure blocks. In either form, Ba(3)Si(4)H(x) is classified as an interstitial hydride. Polyanionic hydrides in which H is covalently attached to Si remain elusive. PMID:25247666

  1. Practical and Efficient Synthesis of α-Aminophosphonic Acids Containing 1,2,3,4-Tetrahydroquinoline or 1,2,3,4-Tetrahydroisoquinoline Heterocycles.

    PubMed

    Ordóñez, Mario; Arizpe, Alicia; Sayago, Fracisco J; Jiménez, Ana I; Cativiela, Carlos

    2016-01-01

    We report here a practical and efficient synthesis of α-aminophosphonic acid incorporated into 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline heterocycles, which could be considered to be conformationally constrained analogues of pipecolic acid. The principal contribution of this synthesis is the introduction of the phosphonate group in the N-acyliminium ion intermediates, obtained from activation of the quinoline and isoquinoline heterocycles or from the appropriate δ-lactam with benzyl chloroformate. Finally, the hydrolysis of phosphonate moiety with simultaneous cleavage of the carbamate afforded the target compounds. PMID:27589713

  2. Crystallographic analysis of the intact metal centres [3Fe-4S](1+/0) and [4Fe-4S](2+/1+) in a Zn(2+) -containing ferredoxin.

    PubMed

    Frazão, Carlos; Aragão, David; Coelho, Ricardo; Leal, Sónia S; Gomes, Cláudio M; Teixeira, Miguel; Carrondo, Maria Arménia

    2008-03-01

    Detailed structural models of di-cluster seven-iron ferredoxins constitute a valuable resource for folding and stability studies relating the metal cofactors' role in protein stability. The here reported, hemihedric twinned crystal structure at 2.0 A resolution from Acidianus ambivalens ferredoxin, shows an integral 103 residues, physiologically relevant native form composed by a N-terminal extension comprising a His/Asp Zn(2+) site and the ferredoxin (betaalphabeta)(2) core, which harbours intact clusters I and II, a [3Fe-4S](1+/0) and a [4Fe-4S](2+/1+) centres. This is in contrast with the previously available ferredoxin structure from Sulfolofus tokodai, which was obtained from an artificial oxidative conversion with two [3Fe-4S](1+/0) centres and poor definition around cluster II. PMID:18258200

  3. Li-Ion Conduction and Stability of Perovskite Li3/8Sr7/16Hf1/4Ta3/4O3.

    PubMed

    Huang, Bing; Xu, Biyi; Li, Yutao; Zhou, Weidong; You, Ya; Zhong, Shengwen; Wang, Chang-An; Goodenough, John B

    2016-06-15

    A solid Li-ion conductor with a high room temperature Li-ion conductivity and small interfacial resistance is required for its application in next-generation Li-ion batteries. Here, we prepared a cubic perovskite-related oxide with the general formula Li3/8Sr7/16Hf1/4Ta3/4O3 (LSHT) by a conventional solid-state reaction method, which was studied by X-ray diffraction, electrochemical impedance spectroscopy, and (7)Li MAS NMR. Li3/8Sr7/16Hf1/4Ta3/4O3 has a high Li-ion conductivity of 3.8 × 10(-4) S cm(-1) at 25 °C and a low activation energy of 0.36 eV in the temperature range 298-430 K. It exhibits both high stability and small interfacial resistance with commercial organic liquid electrolytes, which makes it promising as a separator in Li-ion batteries. PMID:27215282

  4. Preparation of 1,3,5-triamino-2,4,6-trinitrobenzene from 3,5-dichloroanisole

    DOEpatents

    Ott, D.G.; Benziger, T.M.

    1991-03-05

    Preparation of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) from 3,5-dichloroanisole is described. Nitration of 3,5-dichloroanisole under relatively mild conditions gave 3,5-dichloro-2,4,6-trinitroanisole in high yield and purity. Ammonolysis of this latter compound gave the desired TATB. Another route to TATB was through the treatment of the 3,5-dichloro-2,4,6-trinitroanisole with thionyl chloride and dimethylformamide to yield 1,3,5-trichloro-2,4,6-trinitrobenzene. Ammonolysis of this product produced TATB. 8 figures.

  5. 3-tert-Butyl 5-methyl (2R,4S,5R)-2-(4-methoxyphenyl)-4-(3-nitrophenyl)-1,3-oxazolidine-3,5-dicarboxylate

    PubMed Central

    Montiel-Smith, Sara; Bernès, Sylvain; Sandoval-Ramírez, Jesús; Meza-Reyes, Socorro; Dubois, Joëlle

    2012-01-01

    The title mol­ecule, C23H26N2O8, was synthesized in three steps starting from m-nitro­cinnamic acid. The central oxazolidine ring adopts an almost perfect envelope conformation with the O atom as the flap [puckering parameter ϕ = 0.3 (6)°]. The dihedral angle formed by the benzene rings is 61.81 (9)°. In the crystal, mol­ecules are connected into double chains parallel to [010] by C—H⋯O hydrogen bonds. The absolute configuration was assigned from the synthetic procedure. PMID:23284466

  6. Mitochondria Targeted Peptides Protect Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Neurotoxicity

    PubMed Central

    Yang, Lichuan; Zhao, Kesheng; Calingasan, Noel Y.; Luo, Guoxiong; Szeto, Hazel H.

    2009-01-01

    Abstract A large body of evidence suggests that mitochondrial dysfunction and oxidative damage play a role in the pathogenesis of Parkinson's disease (PD). A number of antioxidants have been effective in animal models of PD. We have developed a family of mitochondria-targeted peptides that can protect against mitochondrial swelling and apoptosis (SS peptides). In this study, we examined the ability of two peptides, SS-31 and SS-20, to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice. SS-31 produced dose-dependent complete protection against loss of dopamine and its metabolites in striatum, as well as loss of tyrosine hydroxylase immunoreactive neurons in substantia nigra pars compacta. SS-20, which does not possess intrinsic ability in scavenging reactive oxygen species, also demonstrated significant neuroprotective effects on dopaminergic neurons of MPTP-treated mice. Both SS-31 and SS-20 were very potent (nM) in preventing MPP+ (1-methyl-4-phenylpyridinium)-induced cell death in cultured dopamine cells (SN4741). Studies with isolated mitochondria showed that both SS-31 and SS-20 prevented MPP+-induced inhibition of oxygen consumption and ATP production, and mitochondrial swelling. These findings provide strong evidence that these neuroprotective peptides, which target both mitochondrial dysfunction and oxidative damage, are a promising approach for the treatment of PD. Antioxid. Redox Signal. 11, 2095–2104. PMID:19203217

  7. All-Carbon [3+3] Oxidative Annulations of 1,3-Enynes by Rhodium(III)-Catalyzed C-H Functionalization and 1,4-Migration.

    PubMed

    Burns, David J; Best, Daniel; Wieczysty, Martin D; Lam, Hon Wai

    2015-08-17

    1,3-Enynes containing allylic hydrogens cis to the alkyne function as three-carbon components in rhodium(III)-catalyzed, all-carbon [3+3] oxidative annulations to produce spirodialins. The proposed mechanism of these reactions involves the alkenyl-to-allyl 1,4-rhodium(III) migration. PMID:26224377

  8. All-Carbon [3+3] Oxidative Annulations of 1,3-Enynes by Rhodium(III)-Catalyzed C–H Functionalization and 1,4-Migration**

    PubMed Central

    Burns, David J; Best, Daniel; Wieczysty, Martin D; Lam, Hon Wai

    2015-01-01

    1,3-Enynes containing allylic hydrogens cis to the alkyne function as three-carbon components in rhodium(III)-catalyzed, all-carbon [3+3] oxidative annulations to produce spirodialins. The proposed mechanism of these reactions involves the alkenyl-to-allyl 1,4-rhodium(III) migration. PMID:26224377

  9. Biodegradation of the Hexahydro-1,3,5-Trinitro-1,3,5-Triazine Ring Cleavage Product 4-Nitro-2,4-Diazabutanal by Phanerochaete chrysosporium

    PubMed Central

    Fournier, Diane; Halasz, Annamaria; Spain, Jim; Spanggord, Ronald J.; Bottaro, Jeffrey C.; Hawari, Jalal

    2004-01-01

    Initial denitration of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by Rhodococcus sp. strain DN22 produces CO2 and the dead-end product 4-nitro-2,4-diazabutanal (NDAB), OHCNHCH2NHNO2, in high yield. Here we describe experiments to determine the biodegradability of NDAB in liquid culture and soils containing Phanerochaete chrysosporium. A soil sample taken from an ammunition plant contained RDX (342 μmol kg−1), HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine; 3,057 μmol kg−1), MNX (hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine; 155 μmol kg−1), and traces of NDAB (3.8 μmol kg−1). The detection of the last in real soil provided the first experimental evidence for the occurrence of natural attenuation that involved ring cleavage of RDX. When we incubated the soil with strain DN22, both RDX and MNX (but not HMX) degraded and produced NDAB (388 ± 22 μmol kg−1) in 5 days. Subsequent incubation of the soil with the fungus led to the removal of NDAB, with the liberation of nitrous oxide (N2O). In cultures with the fungus alone NDAB degraded to give a stoichiometric amount of N2O. To determine C stoichiometry, we first generated [14C]NDAB in situ by incubating [14C]RDX with strain DN22, followed by incubation with the fungus. The production of 14CO2 increased from 30 (DN22 only) to 76% (fungus). Experiments with pure enzymes revealed that manganese-dependent peroxidase rather than lignin peroxidase was responsible for NDAB degradation. The detection of NDAB in contaminated soil and its effective mineralization by the fungus P. chrysosporium may constitute the basis for the development of bioremediation technologies. PMID:14766596

  10. Biodegradation of the hexahydro-1,3,5-trinitro-1,3,5-triazine ring cleavage product 4-nitro-2,4-diazabutanal by Phanerochaete chrysosporium.

    PubMed

    Fournier, Diane; Halasz, Annamaria; Spain, Jim; Spanggord, Ronald J; Bottaro, Jeffrey C; Hawari, Jalal

    2004-02-01

    Initial denitration of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by Rhodococcus sp. strain DN22 produces CO2 and the dead-end product 4-nitro-2,4-diazabutanal (NDAB), OHCNHCH2NHNO2, in high yield. Here we describe experiments to determine the biodegradability of NDAB in liquid culture and soils containing Phanerochaete chrysosporium. A soil sample taken from an ammunition plant contained RDX (342 micromol kg(-1)), HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine; 3,057 micromol kg(-1)), MNX (hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine; 155 micromol kg(-1)), and traces of NDAB (3.8 micromol kg(-1)). The detection of the last in real soil provided the first experimental evidence for the occurrence of natural attenuation that involved ring cleavage of RDX. When we incubated the soil with strain DN22, both RDX and MNX (but not HMX) degraded and produced NDAB (388 +/- 22 micromol kg(-1)) in 5 days. Subsequent incubation of the soil with the fungus led to the removal of NDAB, with the liberation of nitrous oxide (N2O). In cultures with the fungus alone NDAB degraded to give a stoichiometric amount of N2O. To determine C stoichiometry, we first generated [14C]NDAB in situ by incubating [14C]RDX with strain DN22, followed by incubation with the fungus. The production of 14CO2 increased from 30 (DN22 only) to 76% (fungus). Experiments with pure enzymes revealed that manganese-dependent peroxidase rather than lignin peroxidase was responsible for NDAB degradation. The detection of NDAB in contaminated soil and its effective mineralization by the fungus P. chrysosporium may constitute the basis for the development of bioremediation technologies. PMID:14766596

  11. Synthesis, molecular structure and photoluminescence properties of 1,2-diphenyl-4-(3-methoxyphenyl)-1,3-cyclopentadiene

    NASA Astrophysics Data System (ADS)

    Ye, Junwei; Deng, Dai; Gao, Yuan; Wang, Xiaoxiao; Yang, Lijian; Lin, Yuan; Ning, Guiling

    2015-01-01

    1,2-Diphenyl-4-(3-methoxyphenyl)-1,3-cyclopentadiene (DPMPCP) was synthesized via aldol condensation reaction followed by cyclization and dehydration reaction. Its structure was characterized by 1H NMR, 13C NMR spectra, high-resolution mass spectrometry and single-crystal X-ray diffraction. The UV-vis absorption and photoluminescence spectra of DPMPCP in solution and aggregation state were studied. It shows solvent-dependent fluorescence emission and aggregation-induced emission enhancement (AIEE) characteristic when DPMPCP aggregated in water/acetonitrile mixture or in crystals. The crystal structure analysis reveals combination effects of J-aggregation molecule stacking and restriction of intramolecular rotation by intermolecular interactions on AIEE. Additionally, the thermal stability, electrochemical property and DFT calculation of DPMPCP were investigated.

  12. Regulation of autophagy in cardiomyocytes by Ins(1,4,5)P(3) and IP(3)-receptors.

    PubMed

    Wong, Albert; Grubb, David R; Cooley, Nicola; Luo, Jieting; Woodcock, Elizabeth A

    2013-01-01

    Autophagy is a process that removes damaged proteins and organelles and is of particular importance in terminally differentiated cells such as cardiomyocytes, where it has primarily a protective role. We investigated the involvement of inositol(1,4,5)trisphosphate (Ins(1,4,5)P(3)) and its receptors in autophagic responses in neonatal rat ventricular myocytes (NRVM). Treatment with the IP(3)-receptor (IP(3)-R) antagonist 2-aminoethoxydiphenyl borate (2-APB) at 5 or 20 μmol/L resulted in an increase in autophagosome content, defined as puncta labeled by antibody to microtubule associated light chain 3 (LC3). 2-APB also increased autophagic flux, indicated by heightened LC3II accumulation, which was further enhanced by bafilomycin (10nmol/L). Expression of Ins(1,4,5)P(3) 5-phosphatase (IP(3)-5-Pase) to deplete Ins(1,4,5)P(3) also increased LC3-labeled puncta and LC3II content, suggesting that Ins(1,4,5)P(3) inhibits autophagy. The IP(3)-R can act as an inhibitory scaffold sequestering the autophagic effector, beclin-1 to its ligand binding domain (LBD). Expression of GFP-IP(3)-R-LBD inhibited autophagic signaling and furthermore, beclin-1 co-immunoprecipitated with the IP(3)-R-LBD. A mutant GFP-IP(3)-R-LBD with reduced ability to bind Ins(1,4,5)P(3) bound beclin-1 and inhibited autophagy similarly to the wild type sequence. These data provide evidence that Ins(1,4,5)P(3) and IP(3)-R act as inhibitors of autophagic responses in cardiomyocytes. By suppressing autophagy, IP(3)-R may contribute to cardiac pathology. PMID:23137780

  13. Design, synthesis, and characterization of (1-(4-aryl)- 1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates against Mycobacterium tuberculosis.

    PubMed

    Venugopala, Katharigatta N; Dharma Rao, G B; Bhandary, Subhrajyoti; Pillay, Melendhran; Chopra, Deepak; Aldhubiab, Bandar E; Attimarad, Mahesh; Alwassil, Osama Ibrahim; Harsha, Sree; Mlisana, Koleka

    2016-01-01

    The novel (1-(4-aryl)-1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives were synthesized by the click reaction of the dihydropyrimidinones, bearing a terminal alkynyl group, with various substituted aryl azides at room temperature using a catalytic amount of Cu(OAc)2 and sodium ascorbate in a 1:2 ratio of acetone and water as a solvent. The newly synthesized compounds were characterized by a number of spectroscopic techniques, such as infrared, liquid chromatography-mass spectrometry, (1)H, and (13)C nuclear magnetic resonance along with single crystal X-ray diffraction. The current procedure for the synthesis of 1,2,3-triazole hybrids with dihydropyrimidinones is appropriate for the synthesis of a library of analogs 7a-l and the method accessible here is operationally simple and has excellent yields. The title compounds 7a-l were evaluated for their in vitro antitubercular activity against H37RV and multidrug-resistant strains of Mycobacterium tuberculosis by resazurin microplate assay plate method and it was found that compound 7d was promising against H37RV and multidrug-resistant strains of M. tuberculosis at 10 and 15 μg/mL, respectively. PMID:27601885

  14. Design, synthesis, and characterization of (1-(4-aryl)- 1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates against Mycobacterium tuberculosis

    PubMed Central

    Venugopala, Katharigatta N; Dharma Rao, G B; Bhandary, Subhrajyoti; Pillay, Melendhran; Chopra, Deepak; Aldhubiab, Bandar E; Attimarad, Mahesh; Alwassil, Osama Ibrahim; Harsha, Sree; Mlisana, Koleka

    2016-01-01

    The novel (1-(4-aryl)-1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives were synthesized by the click reaction of the dihydropyrimidinones, bearing a terminal alkynyl group, with various substituted aryl azides at room temperature using a catalytic amount of Cu(OAc)2 and sodium ascorbate in a 1:2 ratio of acetone and water as a solvent. The newly synthesized compounds were characterized by a number of spectroscopic techniques, such as infrared, liquid chromatography-mass spectrometry, 1H, and 13C nuclear magnetic resonance along with single crystal X-ray diffraction. The current procedure for the synthesis of 1,2,3-triazole hybrids with dihydropyrimidinones is appropriate for the synthesis of a library of analogs 7a-l and the method accessible here is operationally simple and has excellent yields. The title compounds 7a-l were evaluated for their in vitro antitubercular activity against H37RV and multidrug-resistant strains of Mycobacterium tuberculosis by resazurin microplate assay plate method and it was found that compound 7d was promising against H37RV and multidrug-resistant strains of M. tuberculosis at 10 and 15 μg/mL, respectively. PMID:27601885

  15. Tunable Aryl Alkyl Ionic Liquids with Weakly Coordinating Tetrakis((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)borate [B(hfip)4 ] Anions.

    PubMed

    Kaliner, Maria; Rupp, Alexander; Krossing, Ingo; Strassner, Thomas

    2016-07-11

    Weakly coordinating borate or aluminate anions have recently been shown to yield interesting properties of the resulting ionic liquids (ILs). The same is true for large phenyl-substituted imidazolium cations, which can be tuned by the choice, position, or number of substituents on the aromatic ring. We were therefore interested to combine these aryl alkyl imidazolium cations with the weakly coordinating tetrakis((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)borate [B(hfip)4 ](-) anions to study the physical properties and viscosities of these ionic liquids. Despite the large size and high molecular weight of these readily available ILs, they are liquid at room temperature and show remarkably low glass transition points and relatively high decomposition temperatures. PMID:27333433

  16. RELAP5-3D Developmental Assessment: Comparison of Versions 4.3.4i and 4.2.1i

    SciTech Connect

    Bayless, Paul David

    2015-10-01

    Figures have been generated comparing the parameters used in the developmental assessment of the RELAP5-3D code using versions 4.3.4i and 4.2.1i. The figures, which are the same as those used in Volume III of the RELAP5-3D code manual, compare calculations using the semi-implicit solution scheme with available experiment data. These figures provide a quick, visual indication of how the code predictions changed between these two code versions and can be used to identify cases in which the assessment judgment may need to be changed in Volume III of the code manual. Changes to the assessment judgments made after reviewing all of the assessment cases are also provided.

  17. New 1,3,4-bisthiadiazolines: Synthesis, characterization and antimicrobial evaluations

    NASA Astrophysics Data System (ADS)

    Yusuf, Mohamad; Kaur, Manvinder; Jain, Payal; Solanki, Indu

    2012-11-01

    The bisthiadiazolines 4a-4g have been synthesized in good yields from the cyclization reactions of bisthiosemicarbazones 3a-3g with acetic anhydride. The condensation reaction of dibenzaldehydes 2a-2g with thiosemicarbazide in alcoholic medium provided 3a-3g and former were obtained from the O-alkylation of 3-hydroxybenzaldehyde with suitable 1,ω-dibromoalkanes under alkaline conditions in the presence of dry EtOH/DMF. The intermediates 3a-3g and bishetrocyclics 4a-4g were also screened for their in vitro antimicrobial activities against seven bacterial strains (Klubsellia pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Straphylococcus aureus, Bacillius subtilis, Pseudomonas fluorescens and Streptoccus pyrogens) and five fungi strains (Aspergillius janus, Pencillium glabrum, Fusarium oxysporum, Aspergillus sclerotiorum, Aspergillus niger). The compounds 3f, 3g, 4f &4g were found to be significantly active against the tested microorganisms.

  18. Prevention of the nigrostriatal toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by inhibitors of 3,4-dihydroxyphenylethylamine transport.

    PubMed

    Mayer, R A; Kindt, M V; Heikkila, R E

    1986-10-01

    The 3,4-dihydroxyphenylethylamine (DA, dopamine) uptake inhibitors GBR 13,069, amfonelic acid, WIN-35,065-2, WIN-35,428, nomifensine, mazindol, cocaine, McN-5908, McN-5847, and McN-5292 were effective in preventing [3H]DA and [3H]1-methyl-4-phenylpyridinium (MPP+) uptake in rat and mouse neostriatal tissue slices. These DA uptake inhibitors also were effective in attenuating the MPP+-induced release of [3H]DA in vitro. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration to mice (6 X 25 mg/kg i.p.) resulted in a large (70-80%) decrement in neostriatal DA. WIN-35,428 (5 mg/kg), GBR 13,069 (10 mg/kg), McN-5292 (5 mg/kg), McN-5908 (2 mg/kg), and amfonelic acid (2 mg/kg), when administered intraperitoneally 30 min prior to each MPTP injection, fully protected against MPTP-induced neostriatal damage. Other DA uptake inhibitors showed partial protection in vivo at the doses selected. Desmethylimipramine did not prevent [3H]MPP+ uptake or MPP+-induced release of [3H]DA in vitro, and did not protect against MPTP neurotoxicity in vivo. These results support the hypothesis put forth previously by others that the active uptake of MPP+ by dopaminergic neurons is necessary for toxicity. PMID:3489072

  19. Synthesis and structural study on (1E,2E,1'E,2'E)-3,3'-bis[(4-bromophenyl)-3,3'-(4-methy-1,2-phenylene diimine)] acetaldehyde dioxime: A combined experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    Topal, T.; Kart, H. H.; Tunay Taşlı, P.; Karapınar, E.

    2015-06-01

    Tetradentate (1E,2E,1'E,2'E)-3,3'-bis[(4-bromophenyl)-3,3'-(4-methy-1,2-phenylene diimine)] acetaldehyde dioxime which possess N4 donor sets derived from the condensation of isonitroso- p-bromoacetophenone and 3,4-diaminotoluene are synthesized and characterized. The characterization of tetradentate Schiff base ligand has been deduced from LC-MS, FTIR, 13C and 1H NMR spectra and elemental analysis. Furthermore, the molecular geometry, infrared and NMR spectra of the title molecule in the ground state have been calculated by using the quantum chemical computational methods such as density functional theory (DFT) and ab initio Hartree-Fock (HF) methods with the 6-31G(d) and 6-311G(d) basis sets. The computed bond lengths and bond angles by using the both methods show the good agreement with each other. Moreover, the vibrational frequencies have been calculated and the scaled values have been compared with the experimental FTIR spectroscopic data. Assignments of the vibrational modes are made on the basis of potential energy distribution (PED) calculated from by using VEDA program. The correlations between the observed and calculated frequencies are in good agreement with each other as well as the correlation of the NMR data.

  20. Translation control during prolonged mTORC1 inhibition mediated by 4E-BP3.

    PubMed

    Tsukumo, Yoshinori; Alain, Tommy; Fonseca, Bruno D; Nadon, Robert; Sonenberg, Nahum

    2016-01-01

    Targeting mTORC1 is a highly promising strategy in cancer therapy. Suppression of mTORC1 activity leads to rapid dephosphorylation of eIF4E-binding proteins (4E-BP1-3) and subsequent inhibition of mRNA translation. However, how the different 4E-BPs affect translation during prolonged use of mTOR inhibitors is not known. Here we show that the expression of 4E-BP3, but not that of 4E-BP1 or 4E-BP2, is transcriptionally induced during prolonged mTORC1 inhibition in vitro and in vivo. Mechanistically, our data reveal that 4E-BP3 expression is controlled by the transcription factor TFE3 through a cis-regulatory element in the EIF4EBP3 gene promoter. CRISPR/Cas9-mediated EIF4EBP3 gene disruption in human cancer cells mitigated the inhibition of translation and proliferation caused by prolonged treatment with mTOR inhibitors. Our findings show that 4E-BP3 is an important effector of mTORC1 and a robust predictive biomarker of therapeutic response to prolonged treatment with mTOR-targeting drugs in cancer. PMID:27319316

  1. Translation control during prolonged mTORC1 inhibition mediated by 4E-BP3

    PubMed Central

    Tsukumo, Yoshinori; Alain, Tommy; Fonseca, Bruno D.; Nadon, Robert; Sonenberg, Nahum

    2016-01-01

    Targeting mTORC1 is a highly promising strategy in cancer therapy. Suppression of mTORC1 activity leads to rapid dephosphorylation of eIF4E-binding proteins (4E-BP13) and subsequent inhibition of mRNA translation. However, how the different 4E-BPs affect translation during prolonged use of mTOR inhibitors is not known. Here we show that the expression of 4E-BP3, but not that of 4E-BP1 or 4E-BP2, is transcriptionally induced during prolonged mTORC1 inhibition in vitro and in vivo. Mechanistically, our data reveal that 4E-BP3 expression is controlled by the transcription factor TFE3 through a cis-regulatory element in the EIF4EBP3 gene promoter. CRISPR/Cas9-mediated EIF4EBP3 gene disruption in human cancer cells mitigated the inhibition of translation and proliferation caused by prolonged treatment with mTOR inhibitors. Our findings show that 4E-BP3 is an important effector of mTORC1 and a robust predictive biomarker of therapeutic response to prolonged treatment with mTOR-targeting drugs in cancer. PMID:27319316

  2. Synthesis and cytotoxicity testing of novel 2-(3-substituted-6-chloro-1,1-dioxo-1,4,2-benzodithiazin-7-yl)-3-phenyl-4(3H)-quinazolinones.

    PubMed

    Pomarnacka, Elzbieta; Maruszak, Magdalena; Langowska, Karolina; Reszka, Przemyslaw; Bednarski, Patrick J

    2008-08-01

    A new series of thirteen 2-[3-(substituted amino)-6-chloro-1,1-dioxo-1,4,2-benzodithiazin-7-yl]-3-phenyl-4(3H)-quinazolinones 4-16 were prepared in order to evaluate their cytotoxic activity against 12 human cancer cell lines. The bioassay indicated that the quinazolinone derivatives 5, 8-12, 15, and 16 possess cancer-cell growth-inhibitory properties. Compounds 5 and 12 showed a high level of selectivity for certain cell lines. The most active compounds 9, 10, 15, and 16 showed moderate antiproliferative activity and were approximately 4-fold less potent than cisplatin. PMID:18618486

  3. Cd(II) complexes with different nuclearity and dimensionality based on 3-hydrazino-4-amino-1,2,4-triazole

    NASA Astrophysics Data System (ADS)

    Xu, Cai-Xia; Zhang, Jian-Guo; Yin, Xin; Jin, Xin; Li, Tong; Zhang, Tong-Lai; Zhou, Zun-Ning

    2015-03-01

    A series of zero- to two-dimensional Cd(II) coordination compounds have been synthesized by the reaction of Cd(II) salts and 3-hydrazino-4-amino-1,2,4-triazole di-hydrochloride (HATr·2HCl). [CdCl2(HATr)2] (1) and [Cd2Cl4(HATr)2(H2O)2] (2) have discrete mononuclear and binuclear structures, respectively. [Cd(HATr)2(ClO4)2]n (3) presents polymeric 1-D chain and [Cd2(NO3)2Cl2(HATr)2]n (4) shows 2-D frameworks. All Cd(II) ions exhibit distorted octahedral configurations in 1-3, whilst both hexa and heptacoordinated Cd(II) are formed in 4. The HATr ligands adopt chelating coordinated mode in 1, while tri-dentate bridging-chelating mode in 2-4. The chloride ion is a mono-coordinated ligand in 1 and 2, but it bridges two adjacent metal ions in 4. Furthermore, thermal behaviors have been investigated and the results reveal that all complexes have good thermal stability. The impact sensitivity test indicates that complex 3 is sensitive to impact stimuli.

  4. Syntheses, spectral, X-ray and DFT studies of 5-benzyl-N-phenyl-1,3,4-thiadiazol-2-amine, 2-(5-phenyl-1,3,4-thiadiazol-2-yl) pyridine and 2-(5-methyl-1,3,4-thiadiazole-2-ylthio)-5-methyl-1,3,4-thiadiazole obtained by Mn(II) catalyzed reactions

    NASA Astrophysics Data System (ADS)

    Dani, R. K.; Bharty, M. K.; Kushawaha, S. K.; Paswan, S.; Prakash, Om; Singh, Ranjan K.; Singh, N. K.

    2013-12-01

    New compounds 5-benzyl-N-phenyl-1,3,4-thiadiazol-2-amine (Bptha, 1), 2-(5-phenyl-1,3,4-thiadiazol-2-yl) pyridine (Pthp, 2) and 2-(5-methyl-1,3,4-thiadiazole-2-ylthio)-5-methyl-1,3,4-thiadiazole (Mtmth, 3) have been synthesized and characterized with the aid of elemental analyses, IR, NMR and single crystal X-ray data. The structure of compounds 1, 2 and 3 are stabilized via intramolecular as well as intermolecular hydrogen bonding and crystallize in monoclinic system with space group P 1, P21/n and P 1, respectively. During the course of reaction, the substituted thiosemicarbazide/thiohydrazide get cyclized into the corresponding thiadiazole in the presence of manganese(II) nitrate via loss of H2O to yield compounds 1 and 2. However condensation occurred in the case of 5-methyl-1,3,4-thiadiazole-2-thiol which yielded 2-(5-methyl-1,3,4-thiadiazole-2-ylthio)-5-methyl-1,3,4-thiadiazole (3) by loss of one mole of H2S from two moles of 5-methyl-1,3,4-thiadiazole-2-thiol in the presence of manganese(II) acetate. The geometry optimization has been performed using DFT method and geometrical parameters thus obtained for the compounds have been compared with their single crystal X-ray data. The negative values of HOMO and LUMO energies for the molecules indicate that they are stable. The electronic transition from the ground state to the excited state due to a transfer of electrons from the HOMO to LUMO levels is mainly associated with the π⋯π transition.

  5. Interaction of TIM4 and TIM3 induces T helper 1 cell apoptosis.

    PubMed

    Ge, Rong-Ti; Zeng, Lu; Mo, Li-Hua; Xu, Ling-Zhi; Zhang, Huan-Ping; Yu, Hai-Qiong; Zhang, Min; Liu, Zhi-Gang; Liu, Zhan-Ju; Yang, Ping-Chang

    2016-04-01

    The T helper 1 (Th1) polarization plays a critical role in the pathogenesis of a number of inflammatory disorders in the body; the remedies in the correction of polarized Th1 cells are limited. This study aims to investigate the role of T cell immunoglobulin mucin domain molecule 4 (TIM4) in the induction of Th1 cell apoptosis. In this study, polarized Th1 cells were generated from naive Th1 cells from the mouse spleen. Recombinant TIM4 was added to the culture to stimulate the polarized Th1 cells. The apoptosis of Th1 cells was assessed by flow cytometry. The expression of FasL was analyzed by chromatin immunoprecipitation, real time RT-PCR, and Western blotting. The results showed that the polarized Th1 cells expressed high levels of TIM3. After exposure of the polarized Th1 cells to TIM4 in the culture, a complex of TIM3 and TIM4 was detected on the surface of Th1 cells, which induced the Th1 cell apoptosis. The engagement of TIM3 by TIM4 increased p300 phosphorylation in Th1 cells, which further increased the levels of Fas ligand in the cells and induced Th1 cell apoptosis. In conclusion, TIM4 binds TIM3 on the surface of polarized Th1 cells to induce Th1 cell apoptosis, which may contribute to the development of Th2-dominant immune disorders. PMID:26403707

  6. Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist.

    PubMed

    De Savi, Chris; Bradbury, Robert H; Rabow, Alfred A; Norman, Richard A; de Almeida, Camila; Andrews, David M; Ballard, Peter; Buttar, David; Callis, Rowena J; Currie, Gordon S; Curwen, Jon O; Davies, Chris D; Donald, Craig S; Feron, Lyman J L; Gingell, Helen; Glossop, Steven C; Hayter, Barry R; Hussain, Syeed; Karoutchi, Galith; Lamont, Scott G; MacFaul, Philip; Moss, Thomas A; Pearson, Stuart E; Tonge, Michael; Walker, Graeme E; Weir, Hazel M; Wilson, Zena

    2015-10-22

    The discovery of an orally bioavailable selective estrogen receptor downregulator (SERD) with equivalent potency and preclinical pharmacology to the intramuscular SERD fulvestrant is described. A directed screen identified the 1-aryl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole motif as a novel, druglike ER ligand. Aided by crystal structures of novel ligands bound to an ER construct, medicinal chemistry iterations led to (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid (30b, AZD9496), a clinical candidate with high oral bioavailability across preclinical species that is currently being evaluated in phase I clinical trials for the treatment of advanced estrogen receptor (ER) positive breast cancer. PMID:26407012

  7. Preparation data of the bromodomains BRD3(1), BRD3(2), BRD4(1), and BRPF1B and crystallization of BRD4(1)-inhibitor complexes

    PubMed Central

    Hügle, Martin; Lucas, Xavier; Weitzel, Gerhard; Ostrovskyi, Dmytro; Breit, Bernhard; Gerhardt, Stefan; Schmidtkunz, Karin; Jung, Manfred; Schüle, Roland; Einsle, Oliver; Günther, Stefan; Wohlwend, Daniel

    2016-01-01

    This article presents detailed purification procedures for the bromodomains BRD3(1), BRD3(2), BRD4(1), and BRPF1B. In addition we provide crystallization protocols for apo BRD4(1) and BRD4(1) in complex with numerous inhibitors. The protocols described here were successfully applied to obtain affinity data by isothermal titration calorimetry (ITC) and by differential scanning fluorimetry (DSF) as well as structural characterizations of BRD4(1) inhibitor complexes (PDB codes: PDB: 4LYI, PDB: 4LZS, PDB: 4LYW, PDB: 4LZR, PDB: 4LYS, PDB: 5D24, PDB: 5D25, PDB: 5D26, PDB: 5D3H, PDB: 5D3J, PDB: 5D3L, PDB: 5D3N, PDB: 5D3P, PDB: 5D3R, PDB: 5D3S, PDB: 5D3T). These data have been reported previously and are discussed in more detail elsewhere [1], [2]. PMID:27158652

  8. Preparation data of the bromodomains BRD3(1), BRD3(2), BRD4(1), and BRPF1B and crystallization of BRD4(1)-inhibitor complexes.

    PubMed

    Hügle, Martin; Lucas, Xavier; Weitzel, Gerhard; Ostrovskyi, Dmytro; Breit, Bernhard; Gerhardt, Stefan; Schmidtkunz, Karin; Jung, Manfred; Schüle, Roland; Einsle, Oliver; Günther, Stefan; Wohlwend, Daniel

    2016-06-01

    This article presents detailed purification procedures for the bromodomains BRD3(1), BRD3(2), BRD4(1), and BRPF1B. In addition we provide crystallization protocols for apo BRD4(1) and BRD4(1) in complex with numerous inhibitors. The protocols described here were successfully applied to obtain affinity data by isothermal titration calorimetry (ITC) and by differential scanning fluorimetry (DSF) as well as structural characterizations of BRD4(1) inhibitor complexes (PDB codes: PDB: 4LYI, PDB: 4LZS, PDB: 4LYW, PDB: 4LZR, PDB: 4LYS, PDB: 5D24, PDB: 5D25, PDB: 5D26, PDB: 5D3H, PDB: 5D3J, PDB: 5D3L, PDB: 5D3N, PDB: 5D3P, PDB: 5D3R, PDB: 5D3S, PDB: 5D3T). These data have been reported previously and are discussed in more detail elsewhere [1], [2]. PMID:27158652

  9. Synthesis and Antimicrobial Screening of Novel 4-Substituted Phenyl-5-[1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl]-2H-1,2,4-triazole-3-thiones

    PubMed Central

    Bhandari, Namratha; Gaonkar, Santosh L.

    2014-01-01

    The paper describes a convenient method for the preparation of 4-substituted phenyl-5-[1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl]-2H-1,2,4-triazole-3-thiones. The structures of the synthesized compounds are established by the results of LCMS, 1H NMR, 13C NMR, and IR and elemental analyses. The mercaptotriazoles are indicated to be in thione form by 1H NMR spectra. All the synthesized compounds have been screened for antibacterial and antifungal activities. Compounds 12d and 12h exhibit encouraging results, while the remaining compounds show moderate activities. On the basis of spectral studies, formation of 2-amino-1,3,4-thiadiazoles from the isobenzofuran acyl thiosemicarbazides 11(a–h) is ruled out. PMID:27379269

  10. Synthesis and pharmacological investigation of novel 4-(2-methylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H(1)-antihistaminic agents.

    PubMed

    Alagarsamy, V; Rupeshkumar, M; Kavitha, K; Meena, S; Shankar, D; Siddiqui, A A; Rajesh, R

    2008-11-01

    A series of novel 1-substituted-4-(2-methylphenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones were synthesized by the cyclization of 2-hydrazino-3-(2-methylphenyl)-3H-quinazolin-4-one with various one carbon donors. The starting material 2-hydrazino-3-(2-methylphenyl)-3H-quinazolin-4-one was synthesized from 2-methyl aniline by a novel innovative route. The title compounds were tested for their in vivo H(1)-antihistaminic activity on guinea pigs; all the tested compounds protected the animals from histamine-induced bronchospasm significantly. Compound 1-methyl-4-(2-methylphenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (II) emerged as the most active compound of the series and it is more potent (72.45%) when compared to the reference standard chlorpheniramine maleate (71%). Compound II showed negligible sedation (11%) when compared to chlorpheniramine maleate (30%). Hence it could serve as the prototype molecule for further development as a new class of H(1)-antihistaminic agents. PMID:18031870

  11. CYP4Z1 3'UTR represses migration of human breast cancer cells.

    PubMed

    Wang, Bingyu; Zheng, Lufeng; Chou, Jinjiang; Li, Cheng; Zhang, Yan; Meng, Xia; Xi, Tao

    2016-09-16

    To investigate the effects of CYP4Z1 3'UTR in migration of breast cancer cells, a series of assays were used to confirm that overexpression of CYP4Z1 3'UTR could suppress the capacity of migration and adhesion of MCF-7 and MDA-MB-231 cells. EMT (Epithelial-mesenchymal transition)-related proteins were regulated by CYP4Z1 3'UTR. Mesenchyma markers like Vimentin, MMP-2, and MMP-9 were down-regulated, while the expression of E-cadherin was up-regulated with CYP4Z1 3'UTR overexpression. Notably, luciferase reporter and qRT-PCR assays were applied to verify that CYP4Z1 3'UTR was the potential target of miR-9. In addition, our results showed that CYP4Z1 3'UTR repressed the expression of E-cadherin in a miRNA-dependent manner. Combining with our previous study, we have discovered the underlying link between CYP4Z1 and E-cadherin. Therefore, those preliminary data suggest that CYP4Z1 3'UTR could inhibit the migration and EMT of breast cancer cells via acting as a ceRNA for E-cadherin. PMID:27520371

  12. 4-Salicylideneamino-3-methyl-1,2,4-triazole-5-thione as a sensor for aniline recognition

    NASA Astrophysics Data System (ADS)

    Kumar, M. Saravana; Tamilarasan, R.; Sreekanth, A.

    2011-07-01

    Tridentate triazole based Schiff base 4-salicylideneamino-3-methyl-1,2,4-triazole-5-thione has been found to selectively detect toxic aromatic amines such as aniline and benzene-1,4-diamine by simple titration techniques like UV-visible, fluorescence spectral studies (PL) and 1H NMR titrations. The Schiff base receptor utilizes, thione sulfur, NH-thione and the phenolic hydroxyl group to form hydrogen bonded adduct of aniline and benzene-1,4-diamine with high binding affinity, followed by a slow removal of the corresponding hydrogens thus providing a promising candidate and an unique receptor for toxic aromatic amines.

  13. A toxological study of 3,6-BIS(3,5-Dimethyl-1-1-Pyrazolyl)1,2-Dihydro-1,2,4,5-Tetrazine

    SciTech Connect

    London, J.E.

    1993-03-01

    The acute oral LD[sub 30/50] values for 3,6-BIS(3,5-Dimethyl-1-Pyrazolyl)-1,2-Dihydro-1,2,4,5-Tetrazine BIS(DMP)DHT are greater than 5g/kg. According to classical guidelines, the material would be considered only slightly toxic or practically nontoxic in both rats and mice. The sensitization study in the guinea pig did not show BIS(DMP)SHT to have potential sensitizing effects. Skin application studies on the rabbit demonstrated the material was cutaneously nonirritating. This material was also nonirritating in the rabbit eye application studies.

  14. A toxological study of 3,6-BIS(3,5-Dimethyl-1-1-Pyrazolyl)1,2-Dihydro-1,2,4,5-Tetrazine

    SciTech Connect

    London, J.E.

    1993-03-01

    The acute oral LD{sub 30/50} values for 3,6-BIS(3,5-Dimethyl-1-Pyrazolyl)-1,2-Dihydro-1,2,4,5-Tetrazine BIS(DMP)DHT are greater than 5g/kg. According to classical guidelines, the material would be considered only slightly toxic or practically nontoxic in both rats and mice. The sensitization study in the guinea pig did not show BIS(DMP)SHT to have potential sensitizing effects. Skin application studies on the rabbit demonstrated the material was cutaneously nonirritating. This material was also nonirritating in the rabbit eye application studies.

  15. 2-(4-Chlorobenzyl)-6-arylimidazo[2,1-b][1,3,4]thiadiazoles: synthesis, cytotoxic activity and mechanism of action.

    PubMed

    Kumar, Sujeet; Hegde, Mahesh; Gopalakrishnan, Vidya; Renuka, Vinaya Kumar; Ramareddy, Sureshbabu A; De Clercq, Erik; Schols, Dominique; Gudibabande Narasimhamurthy, Anil Kumar; Raghavan, Sathees C; Karki, Subhas S

    2014-09-12

    The cytotoxic activity of a new series of 2-(4'-chlorobenzyl)-5,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazoles against different human and murine cancer cell lines is reported. Among the tested compounds, two derivatives namely 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde 4i and 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate 5i emerged as the most potent against all the cell lines. To investigate the mechanism of action, we selected compounds 4i for cell cycle study, analysis of mitochondrial membrane potential and Annexin V-FITC flow cytometric analysis and DNA fragmentation assay. Results showed that 4i induced cytotoxicity by inducing apoptosis without arresting the cell cycle. PMID:25064346

  16. 2,6-Dihy-droxy-4-oxo-2-(pyridin-1-ium-3-yl)-4H-1,3,2-benzodioxaborinin-2-ide 0.67-hydrate.

    PubMed

    Garcia-Grajeda, Blanca A; Höpfl, Herbert; Guerrero-Alvarez, Jorge A; Campos-Gaxiola, José J; Cruz-Enríquez, Adriana

    2014-04-01

    The asymmetric unit of the title compound, C12H10BNO5·0.67H2O, contains three independent pyridinylboronic acid esters adopting zwitterionic forms and two water mol-ecules. The six-membered heterocyclic rings in the boronic esters have half-chair conformations and the deviations of the B atoms from the boronate mean planes range from 0.456 (3) to 0.657 (3) Å. All of the B atoms have tetra-hedral coordination environments, with B-O and B-C bond lengths of 1.446 (4)-1.539 (3) and 1.590 (5)-1.609 (5) Å, respectively. In the crystal, the ester and water mol-ecules are linked into a three-dimensional network by a large number of O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds. The crystal packing is further accomplished by π-π inter-actions, with centroid-centroid distances of 3.621 (4)-3.787 (4) Å. PMID:24826112

  17. 2,6-Dihy­droxy-4-oxo-2-(pyridin-1-ium-3-yl)-4H-1,3,2-benzodioxaborinin-2-ide 0.67-hydrate

    PubMed Central

    Garcia-Grajeda, Blanca A.; Höpfl, Herbert; Guerrero-Alvarez, Jorge A.; Campos-Gaxiola, José J.; Cruz-Enríquez, Adriana

    2014-01-01

    The asymmetric unit of the title compound, C12H10BNO5·0.67H2O, contains three independent pyridinylboronic acid esters adopting zwitterionic forms and two water mol­ecules. The six-membered heterocyclic rings in the boronic esters have half-chair conformations and the deviations of the B atoms from the boronate mean planes range from 0.456 (3) to 0.657 (3) Å. All of the B atoms have tetra­hedral coordination environments, with B—O and B—C bond lengths of 1.446 (4)–1.539 (3) and 1.590 (5)–1.609 (5) Å, respectively. In the crystal, the ester and water mol­ecules are linked into a three-dimensional network by a large number of O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds. The crystal packing is further accomplished by π–π inter­actions, with centroid–centroid distances of 3.621 (4)–3.787 (4) Å. PMID:24826112

  18. A survey of the lone pair effect on the ring geometry of 1,2,4-triazoles and analogous 1,2,3-triazoles and imidazoles. The structures of 1-methyl-5-amino-3-methylthio-1,2,4-triazole, 1-phenyl-5-amino-3-methylthio-1,2,4-triazole and 1-(4-methylbenzyl)-3-amino-5-methylthio-1,2,4-triazole

    NASA Astrophysics Data System (ADS)

    Kálmán, A.; Argay, Gy.

    1983-11-01

    The structures of the title compounds have been established by X-ray crystallography from diffractometer data. Crystals of the first ( I), C 4H 8N 4S, are monoclinic, space group P2 1/ c, with a = 8.166(2), b = 10.481(1), c = 8.585(1) Å, β = 109.33(2)°, Z = 4, D c = 1.381 g cm -3. Crystals of the second ( II), C 9H 10N 4S, are monoclinic, space group P2 1/ c, with a = 11.850(4), b = 7.898(1), c = 23.981 (6) Å, β = 117.23(2)°, Z = 8, D c = 1.373 g cm -3. Crystals of the third ( III), C 11H 14N 4S 1 are also monoclinic, space group P2 1/ c with a = 12.829(3), b = 8.348(1), c = 11.088(4) Å, β = 94.40(4)°, Z = 4, Dc = 1.314 g cm -3. The structures, determined by direct methods ( I, III) and Patterson synthesis ( II) were refined to R = 0.039 for 1070 reflections of I, R = 0.040 for 2792 reflections of II and R = 0.041 for 1900 reflections of III. The characteristic features of the planar five-membered rings are studied in comparison with the analogous 1,2,3-triazoles and imidazoles. It is shown that these planar rings exhibit only two patterns of the endocyclic bond angles induced dominantly by the number and relative position of the N-lone pairs. A similar effect of the double bonds (attached to C atoms) is also discussed.

  19. DIETHYLDITHIOCARBAMATE POTENTIATES THE NEUROTOXICITY OF IN VIVO 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE AND OF IN VITRO 1-METHYL-4-PHENYLPYRIDINIUM

    EPA Science Inventory

    Diethyldithiocarbamic acid (DDC), a dithiocarbamate, potentiates the neurotoxicity of 1-methyl-r-pheny-1,2,3,6-tetrahydropyridine (MPTP) in vivo and of its major metabolite, 1,-methyl-4-phenylpyridinium (MPP+), in bovine adrenal medullary (BAM) cells maintained in culture. ale C5...

  20. Enantiomers of myo-inositol-1,3,4-trisphosphate and myo-inositol-1,4,6 -trisphosphate: stereospecific recognition by cerebellar and platelet myo-inositol-1,4,5-trisphosphate receptors.

    PubMed

    Murphy, C T; Bullock, A J; Lindley, C J; Mills, S J; Riley, A M; Potter, B V; Westwick, J

    1996-11-01

    The naturally occurring tetrakisphosphate myo-inositol-1,3,4, 6-tetrakisphosphate [Ins(1,3,4,6)P4] was able to release Ca2+ from the intracellular stores of permeabilized rabbit platelets but was 40-fold less potent than D-myo-inositol-1,4,5-trisphosphate [Ins(1,4,5)P3]. The Ca2+ releasing activity of Ins(1,3,4,6)P4 was rationalized by envisaging two alternative receptor binding orientations in which the vicinal D-1,6-bisphosphate of Ins(1,3,4,6)P4 mimics the D-4,5-bisphosphate in the Ins(1,4,5)P3 binding conformation. This rationalization predicted that Ins(1,4,5)P3 regioisomers [i.e, D-myo-inositol -1,4,6-trisphosphate [D-Ins(1,4,6)P3] and D-myo-inositol-1,3,6 -trisphosphate [D-Ins(1,3,6)P3

  1. Docking and quantitative structure-activity relationship studies for 3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)aniline, 3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline, and 4-(4-amino-2-fluorophenoxy)-2-pyridinylamine derivatives as c-Met kinase inhibitors.

    PubMed

    Caballero, Julio; Quiliano, Miguel; Alzate-Morales, Jans H; Zimic, Mirko; Deharo, Eric

    2011-04-01

    We have performed docking of 3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)aniline (FPTA), 3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline (FPPA), and 4-(4-amino-2-fluorophenoxy)-2-pyridinylamine (AFPP) derivatives complexed with c-Met kinase to study the orientations and preferred active conformations of these inhibitors. The study was conducted on a selected set of 103 compounds with variations both in structure and activity. Docking helped to analyze the molecular features which contribute to a high inhibitory activity for the studied compounds. In addition, the predicted biological activities of the c-Met kinase inhibitors, measured as IC(50) values were obtained by using quantitative structure-activity relationship (QSAR) methods: Comparative molecular similarity analysis (CoMSIA) and multiple linear regression (MLR) with topological vectors. The best CoMSIA model included steric, electrostatic, hydrophobic, and hydrogen bond-donor fields; furthermore, we found a predictive model containing 2D-autocorrelation descriptors, GETAWAY descriptors (GETAWAY: Geometry, Topology and Atom-Weight AssemblY), fragment-based polar surface area (PSA), and MlogP. The statistical parameters: cross-validate correlation coefficient and the fitted correlation coefficient, validated the quality of the obtained predictive models for 76 compounds. Additionally, these models predicted adequately 25 compounds that were not included in the training set. PMID:21487786

  2. 3-(4-Methoxybenzyl)-1,5-benzo-thiazepin-4(5H)-one.

    PubMed

    Selvakumar, R; Bakthadoss, M; Vijayakumar, S; Murugavel, S

    2013-05-01

    In the title compound, C17H15NO2S, the thia-zepine ring adopts a slightly distorted twist-boat conformation. The dihedral angle between the mean plane of the benzo-thia-zepin ring system and the benzene ring is 65.7 (1)°. In the crystal, pairs of N-H⋯O hydrogen bonds link inversion-related mol-ecules into dimers, generating R2 (2) (8) ring motifs. These dimers are further linked by C-H⋯π and π-π inter-actions [inter-centroid distance between the benzene rings of the benzo-thia-zepine unit = 3.656 (3) Å] into a three-dimensional supra-molecular network. PMID:23723850

  3. 5-(4-Hy-droxy-benzyl-idene)-2,2-dimethyl-1,3-dioxane-4,6-dione.

    PubMed

    Zeng, Wu-Lan

    2010-01-01

    The title compound, C(13)H(12)O(5), was prepared by the reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione and 4-hy-droxy-benz-alde-hyde in ethanol. The 1,3-dioxane ring is in a distorted boat conformation. In the crystal, inversion dimers linked by pairs of O-H⋯O hydrogen bonds generate R(2) (2)(20) rings. PMID:21588666

  4. 4-(4-fluoro-3-phenoxyphenyl)-6-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile and the 6-(4-methylphenyl)- analogue.

    PubMed

    Chopra, Deepak; Mohan, T P; Vishalakshi, B; Guru Row, T N

    2006-09-01

    The crystal structures of the title compounds, viz. C24H14F2N2O2, (I), and C25H17FN2O2, (II), respectively, have been determined in order to unravel the role of an ordered F atom in generating stable supramolecular assemblies. On changing the substitution from fluorine to a methyl group, C-H...F interactions are replaced by C-H...pi interactions, revealing the importance of such weak interactions when present alongside N-H...O and C-H...O hydrogen bonds. The dihedral angle between the planes of the 4-fluorophenyl ring and the pyridine ring is 26.8 (1) degrees in (I), while that between the planes of the 4-methylphenyl and pyridine rings is 29.5 (1) degrees in (II). PMID:16954636

  5. One-dimensional Cu(II) coordination polymers containing C2h-symmetric 1,1':4',1''-terphenyl-3,3'-dicarboxylate linkers.

    PubMed

    Kim, Hyun Chul; Gu, Ja Min; Huh, Seong; Yo, Chul Hyun; Kim, Youngmee

    2015-10-01

    Two new one-dimensional Cu(II) coordination polymers (CPs) containing the C2h-symmetric terphenyl-based dicarboxylate linker 1,1':4',1''-terphenyl-3,3'-dicarboxylate (3,3'-TPDC), namely catena-poly[[bis(dimethylamine-κN)copper(II)]-μ-1,1':4',1''-terphenyl-3,3'-dicarboxylato-κ(4)O,O':O'':O'''] monohydrate], {[Cu(C20H12O4)(C2H7N)2]·H2O}n, (I), and catena-poly[[aquabis(dimethylamine-κN)copper(II)]-μ-1,1':4',1''-terphenyl-3,3'-dicarboxylato-κ(2)O(3):O(3')] monohydrate], {[Cu(C20H12O4)(C2H7N)2(H2O)]·H2O}n, (II), were both obtained from two different methods of preparation: one reaction was performed in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) as a potential pillar ligand and the other was carried out in the absence of the DABCO pillar. Both reactions afforded crystals of different colours, i.e. violet plates for (I) and blue needles for (II), both of which were analysed by X-ray crystallography. The 3,3'-TPDC bridging ligands coordinate the Cu(II) ions in asymmetric chelating modes in (I) and in monodenate binding modes in (II), forming one-dimensional chains in each case. Both coordination polymers contain two coordinated dimethylamine ligands in mutually trans positions, and there is an additional aqua ligand in (II). The solvent water molecules are involved in hydrogen bonds between the one-dimensional coordination polymer chains, forming a two-dimensional network in (I) and a three-dimensional network in (II). PMID:26422225

  6. Synthesis, experimental and theoretical study of the spectroscopic properties in (2E)-3-{3-methoxy-4-[(3-methylbut-2-en-1-yl)oxy]phenyl}-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one

    NASA Astrophysics Data System (ADS)

    Espinoza-Hicks, J. C.; Rodríguez-Valdez, L. M.; Nevárez-Moorillón, G. V.; Camacho-Dávila, A.

    2012-08-01

    We reported the synthesis of (2E)-3-{3-methoxy-4-[(3-methylbut-2-en-1-yl)oxy]phenyl}-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one. The molecular structure and spectroscopic properties of this compound were calculated using the density functional theory (DFT) method with the B3LYP hybrid functional in combination with Pople type 6-311++G(d,p) basis set. The geometry analysis shows that the calculated bond angles and bond distances have a satisfactory relation compared with experimental values. The NMR studies were realized using the GIAO Method, a satisfactory linear correlation was observed for 1H with r = 0.993 and 13C with r = 0.988, finding the highest value for 1H NMR spectrum. The analysis of IR spectra shows a good correlation with the theoretical spectrum. The results show that the DFT-B3LYP/6-311++G(d,p) can describe with a good correlation the spectroscopic properties of the chalcone analyzed.

  7. 3,4-DGE is cytotoxic and decreases HSP27/HSPB1 in podocytes.

    PubMed

    Sanchez-Niño, Maria Dolores; Poveda, Jonay; Sanz, Ana Belen; Carrasco, Susana; Ruiz-Ortega, Marta; Selgas, Rafael; Egido, Jesus; Ortiz, Alberto

    2014-03-01

    Hyperglycemia is the key driver of diabetic complications and increased concentrations of glucose degradation products. The study of peritoneal dialysis solution biocompatibility has highlighted the adverse biological effects of glucose degradation products. Recently, 3,4-dideoxyglucosone-3-ene (3,4-DGE) was identified as the most toxic glucose degradation product in peritoneal dialysis fluids. In addition, 3,4-DGE is present in high-fructose corn syrup, and its precursor 3-deoxyglucosone is increased in diabetes. The role of 3,4-DGE in glomerular injury had not been addressed. We studied the effects of 3,4-DGE on cultured human podocytes and in vivo in mice. 3,4-DGE induced apoptosis in podocytes in a dose- and time-dependent manner. 3,4-DGE promoted the release of cytochrome c from mitochondria and activation of caspase-3. While high glucose concentrations increased the levels of the podocyte intracellular antiapoptotic protein HSP27/HSPB1, 3,4-DGE decreased the expression of podocyte HSP27/HSPB1. Apoptosis induced by 3,4-DGE was caspase-dependent and could be prevented by the broad-spectrum caspase inhibitor zVAD-fmk. Antagonism of Bax by a Ku-70-derived peptide also prevented apoptosis. Intravenous administration of 3,4-DGE to healthy mice resulted in a decreased expression of HSP27/HSPB1 and caspase-3 activation in whole kidney and in podocytes in vivo. In conclusion, 3,4-DGE induces apoptotic cell death in cultured human podocytes, suggesting a potential role in glomerular injury resulting from metabolic disorders. PMID:24337777

  8. New short and general synthesis of three key Maillard flavour compounds: 2-Acetyl-1-pyrroline, 6-acetyl-1,2,3,4-tetrahydropyridine and 5-acetyl-2,3-dihydro-4H-1,4-thiazine.

    PubMed

    Deblander, Jurgen; Van Aeken, Sam; Adams, An; De Kimpe, Norbert; Abbaspour Tehrani, Kourosch

    2015-02-01

    A new general synthetic route towards three key Maillard flavour compounds, namely 2-acetyl-1-pyrroline, 6-acetyl-1,2,3,4-tetrahydropyridine and 5-acetyl-2,3-dihydro-4H-1,4-thiazine, was developed. The key step in the process is the methylenation reaction of azaheterocyclic carboxylic esters by means of dimethyltitanocene, giving rise to intermediate vinyl ethers which can be considered as excellent and stable precursors for the title compounds, as a simple acidic treatment of these precursors suffices to release the characteristic Maillard flavours. PMID:25172717

  9. Synthesis of 3,5-Isoxazolidinediones and 1H-2,3-Benzoxazine-1,4(3H)-diones from Aliphatic Oximes and Dicarboxylic Acid Chlorides

    PubMed Central

    2015-01-01

    The synthesis of the title compounds was carried out by reacting dicarboxylic acid chlorides with oximes in the presence of excess triethylamine. Disubstituted malonyl chlorides gave 2-alkenyl-4,4-dialkyl-3,5-isoxazolidinediones (8a–f) and 2,2′-ethylidene-bis[4,4-dialkyl-3,5-isoxazolidinedione]s (9a–f). Compounds 9 were formed from 8 and its N-unsubstituted 3,5-isoxazolidinedione decomposition product. Phthaloyl chlorides reacted with acetone oxime to yield 3-(1-methylethenyl)-1H-2,3-benzoxazine-1,4(3H)-diones (16a–e). Products 16 spontaneously decomposed to give N-unsubstituted 1H-2,3-benzoxazine-1,4(3H)-diones (17a–e) at rates that were dependent on temperature and solvent. Kinetic studies showed that two of the compounds decomposed by zero-order kinetics under neutral conditions. Butanedioyl chloride did not produce a cyclic product. PMID:24620711

  10. Metabolism of 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) in rodent tissues and in vivo.

    PubMed

    Romaszko, P; Slominska, E M; Orlewska, C; Lipinski, M; Smolenski, R T

    2011-05-01

    Our previous studies identified 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) phosphates in human erythrocytes. We demonstrated formation of these nucleotides by phosphorylation of 4PYR and potential toxicity due to disruption of erythrocyte energy balance. This study aimed to evaluate the ability of the other cell types to phosphorylate 4PYR to characterize function and toxicity of these compounds. Homogenates of rat heart, kidneys, and liver were used to study the rate of 4PYR phosphorylation in the presence of ATP. In another experiment, 4PYR was administered into mouse as repeated subcutaneous injections and into rats as intraperitoneal infusion. After 7 days, heart, liver, kidney, lungs, and skeletal muscle were collected, and the concentration of 4PYR nucleotides was evaluated. HPLC was used to measure 4PYR and 4PYR nucleotides in homogenate and specimens from in vivo experiments. 4PYR was rapidly phosphorylated by the liver homogenate (390 ± 27 nmol/min/g wet wt). Significant rates were reported in the heart and kidneys' homogenates: 34.3 ± 4.3 nmol/min/g and 33.2 ± 9.2 nmol/min/g, respectively. Phosphorylation of 4PYR was almost completely inhibited by adenosine kinase inhibitor 5'-iodotubercidin. Administration of 4PYR in vivo resulted in accumulation of 4PYR monophosphate in the liver, heart, skeletal muscle, and lung (20-220 nmol/g dry wt) except kidney (<1 nmol/g). In contrast to erythrocytes, no 4PYR triphosphate formation (<1 nmol/g) was observed in any of the organs studied. We conclude that not only the erythrocytes but also other cell types are capable of phosphorylating 4PYR to form 4PYR monophosphate. Potential toxicity or physiological role of 4PYR in peripheral organs could be considered, but mechanisms will be different from that in erythrocytes. PMID:21312056

  11. RELAP5-3D Developmental Assessment: Comparison of Versions 4.2.1i and 4.1.3i

    SciTech Connect

    Paul D. Bayless

    2014-06-01

    Figures have been generated comparing the parameters used in the developmental assessment of the RELAP5-3D code using versions 4.2.1i and 4.1.3i. The figures, which are the same as those used in Volume III of the RELAP5-3D code manual, compare calculations using the semi-implicit solution scheme with available experiment data. These figures provide a quick, visual indication of how the code predictions changed between these two code versions and can be used to identify cases in which the assessment judgment may need to be changed in Volume III of the code manual. Changes to the assessment judgments made after reviewing all of the assessment cases are also provided.

  12. Unveiling the sodium intercalation properties in Na1.86□0.14Fe3(PO4)3

    NASA Astrophysics Data System (ADS)

    Essehli, R.; Ben Yahia, H.; Maher, K.; Sougrati, M. T.; Abouimrane, A.; Park, J.-B.; Sun, Y.-K.; Al-Maadeed, M. A.; Belharouak, I.

    2016-08-01

    The new compound Na1.86□0.14Fe3(PO4)3 was successfully synthesized via hydrothermal synthesis and its crystal structure was determined using powder X-ray diffraction data. Na1.86Fe3(PO4)3 was also characterized by operando XRD and Mössbauer spectroscopy, cyclic voltammetry, and galvanostatic cycling. Na1.86Fe3(PO4)3 crystallizes with the alluaudite-type structure with the eight coordinated Na1 and Na2 sodium atoms located within the channels. The combination of the Rietveld- and Mössbauer-analyses confirms that the sodium vacancies in the Na1 site are linked to a partial oxidation of Fe2+ during synthesis. The electrochemical tests indicated that Na1.86Fe3(PO4)3 is a 3 V sodium intercalating cathode. At the current densities of 5, 10, and 20 mA g-1, the material delivers the specific capacities of 109, 97, and 80 mA h g-1, respectively. After 100 charge and discharge cycles, Na1.86Fe3(PO4)3 exhibited good sodium removal and uptake behavior although no optimizations of particle size, morphology, and carbon coating were performed.

  13. Crystal structure of 1-[(2,2-dimethyl-1,3-dioxolan-4-yl)meth-yl]-2-(thia-zol-4-yl)-1H-benzimidazole.

    PubMed

    Gueddar, Hicham; Bouhfid, Rachid; Essassi, El Mokhtar; Saadi, Mohamed; El Ammari, Lahcen

    2015-12-01

    The benzimidazole ring in the title compound, C16H17N3O2S, is almost planar, with the greatest deviation from the mean plane being 0.032 (1) Å. The fused-ring system makes dihedral angles of 19.91 (7) and 24.51 (8)° with the best plane through each of the thia-zol-4-yl and 1,3-dioxolan-4-yl rings, respectively; the latter exhibits an envelope conformation with the methyl-ene C atom being the flap. Finally, the thia-zol-4-yl ring makes a dihedral angle of 33.85 (9)° with the 1,3-dioxolan-4-yl ring. In the crystal, mol-ecules are connected by a pair of C-H⋯π(imidazole) inter-actions to form centrosymmetric aggregates. PMID:26870546

  14. Synthesis and Antimicrobial Activity of Some New Thiadiazoles, Thioamides, 5-Arylazothiazoles and Pyrimido[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines.

    PubMed

    Abdelhamid, Abdou O; El Sayed, Ibrahim E; Hussein, Mohamed Z; Mangoud, Mangoud M

    2016-01-01

    A novel series of 1,3,4-thiadiazoles, 5-arylazothiazoles and hexahydropyrimido-[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines were synthesized via reaction of hydrazonoyl halides with each of alkyl carbothioates, carbothioamides and 7-thioxo-5,6,7,8-tetrahydropyrimido-[4,5-d]pyrimidine-2,4(1H,3H)-diones in the presence of triethylamine. The structures of the newly synthesized compounds were established based on their spectral data, elemental analyses and alternative synthetic routes whenever possible. Also, the newly synthesized compounds were screened for their antimicrobial activity against various microorganisms. PMID:27548118

  15. Development of a new fluorescent probe: 1,3,5,7-tetramethyl-8-(4'-aminophenyl)-4,4-difluoro-4-bora-3a,4a-diaza- s-indacence for the determination of trace nitrite

    NASA Astrophysics Data System (ADS)

    Li, Mengling; Wang, Hong; Zhang, Xian; Zhang, Hua-shan

    2004-03-01

    A new fluorescent probe, 1,3,5,7-tetramethyl-8-(4'-aminophenyl)-4,4-difluoro-4-bora-3a,4a-diaza- s-indacence (TMABODIPY) has been developed for the determination of trace nitrite in terms of the reaction of nitrite with TMABODIPY first in acidic solution and then in alkaline solution to form diazotate, a stable and highly fluorescent reagent. The method offered the advantage of specificity, sensitivity and simplicity. The linear calibration range for nitrite was 8-300 nmol l -1 s with a 3 σ detection limit of 0.65 nmol l -1. The proposed method has been applied to monitor the trace nitrite in drinking water and vegetable without extraction.

  16. Specific features of magnetic properties of Tb1- x Ho x Al3(BO3)4 aluminoborates

    NASA Astrophysics Data System (ADS)

    Eremin, E. V.; Volkov, N. V.; Temerov, V. L.; Gudim, I. A.

    2016-04-01

    Single crystals Tb1- x Ho x Al3(BO3)4 with x = 0, 0.1, 0.5, 0.9, 1 have been grown based on bismuth trimolybdate using a solution-melt method. Their magnetic properties have been studied in the temperature range of 4.2-295 K and magnetic fields to 9 T. The effective magnetic moments μeff|| and μeff⊥ have been determined. It has been found that the temperature dependence of the susceptibility measured experimentally differs from that calculated on the assumption that the contributions of Tb3+ and Ho3+ ions are proportional to fractions from the susceptibilities of TbAl3(BO3)4 and HoAl3(BO3)4, respectively.

  17. New triterpene constituents, foliasalacins A(1)-A(4), B(1)-B(3), and C, from the leaves of Salacia chinensis.

    PubMed

    Yoshikawa, Masayuki; Zhang, Yi; Wang, Tao; Nakamura, Seikou; Matsuda, Hisashi

    2008-07-01

    Four dammarane-type, three lupane-type, and an oleanane-type triterpenes named foliasalacins A(1) (1), A(2) (2), A(3) (3), A(4) (4), B(1) (5), B(2) (6), B(3) (7), and C (8) were isolated from the leaves of Salacia chinensis LINN. collected in Thailand. The structures of new triterpene constituents (1-8) were characterized on the basis of chemical and physiochemical evidence. PMID:18591801

  18. Homology modeling and QSAR analysis of 1,3,4-thiadiazole and 1,3,4-triazole derivatives as carbonic anhydrase inhibitors.

    PubMed

    Akula, N V Murali Krishna; Kumar, Surendra; Singh, Vineet; Tiwari, Meena

    2010-08-01

    Carbonic anhydrase (CA) inhibitors are very interesting target for designing anticancer (hypoxic) and antiglaucoma drugs. In the present study, a 3D homology modeling of human carbonic anhydrase-IX (hCA-IX) isozyme, based upon the crystal structure of murine CA-XIVA (PDB CODE 1RJ5) was performed, as no experimental 3D structures are available. A homology model of hCA-IX was developed and validated. To explore the responsible physicochemical properties of 1,3,4-thiadiazole and 1,3,4-triazole derivatives for carbonic anhydrase inhibition, a quantitative structure activity relationship (QSAR) study was performed having hCA-II and hCA-IX inhibitory activity respectively. In hCA-II and hCA-IX inhibitory activities, four significant models with good correlations (> or = 0.945 & > or = 0.926) were obtained; two models (models 1 and 3) were selected based on statistical criterion. The QSAR study revealed that in case of hCA-II, overall increase in size and volume of molecule, introduction of electropositive surfaces might increase the inhibitory activity, whereas in case of hCA-IX, decreasing the hydrophobicity and introduction of electron releasing substituents might increase the hCA-IX inhibitory activity. PMID:21174951

  19. 27 CFR 555.214 - Storage within types 1, 2, 3, and 4 magazines.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., 3, and 4 magazines. 555.214 Section 555.214 Alcohol, Tobacco Products, and Firearms BUREAU OF... Storage § 555.214 Storage within types 1, 2, 3, and 4 magazines. (a) Explosive materials within a magazine... materials are not to be unpacked or repacked inside a magazine or within 50 feet of a magazine, and must...

  20. 27 CFR 555.214 - Storage within types 1, 2, 3, and 4 magazines.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., 3, and 4 magazines. 555.214 Section 555.214 Alcohol, Tobacco Products, and Firearms BUREAU OF... Storage § 555.214 Storage within types 1, 2, 3, and 4 magazines. (a) Explosive materials within a magazine... materials are not to be unpacked or repacked inside a magazine or within 50 feet of a magazine, and must...

  1. 27 CFR 555.214 - Storage within types 1, 2, 3, and 4 magazines.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., 3, and 4 magazines. 555.214 Section 555.214 Alcohol, Tobacco Products, and Firearms BUREAU OF... Storage § 555.214 Storage within types 1, 2, 3, and 4 magazines. (a) Explosive materials within a magazine... materials are not to be unpacked or repacked inside a magazine or within 50 feet of a magazine, and must...

  2. 27 CFR 555.214 - Storage within types 1, 2, 3, and 4 magazines.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., 3, and 4 magazines. 555.214 Section 555.214 Alcohol, Tobacco Products, and Firearms BUREAU OF... Storage § 555.214 Storage within types 1, 2, 3, and 4 magazines. (a) Explosive materials within a magazine... materials are not to be unpacked or repacked inside a magazine or within 50 feet of a magazine, and must...

  3. 27 CFR 555.214 - Storage within types 1, 2, 3, and 4 magazines.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., 3, and 4 magazines. 555.214 Section 555.214 Alcohol, Tobacco Products, and Firearms BUREAU OF... Storage § 555.214 Storage within types 1, 2, 3, and 4 magazines. (a) Explosive materials within a magazine... materials are not to be unpacked or repacked inside a magazine or within 50 feet of a magazine, and must...

  4. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) regulates CTL activation and memory programming

    PubMed Central

    Sun, Zhifeng; Xiao, Zhengguo

    2013-01-01

    4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the major carcinogens in tobacco. NNK has been associated with various cancers in tobacco users, especially lung cancer. However, the effects of NNK on cytotoxic T lymphocytes (CTLs), the cells responsible for destrcution of maligant and pathogen-infected cells, has not been elucidated. Using transgenic CTLs in vitro and in vivo, we show that NNK can directly affect CTL activation. NNK can enhance the expression of adhesion molecule CD62L in CTLs during their activation in vitro, but has no effects on their expansion and production of effector molecules such as IFN and granzyme B. After transferred into recipient mice, however, the NNK pretreated CTLs suffer an early loss in expansion. The percentage of memory precursors is higher in NNK pretreated CTLs, but the total amount of memory precursors is similar to controls. The final memory CTL population from NNK pretreated CTLs is reduced, but sustains a more central memory phenotype. In conclusion, NNK can affect CTL activation by modulating adhension molecule expression and reducing memory programming. PMID:23673295

  5. Photochemistry of the 1,4-Diphenyl-1,3-butadienes in Ethanol. Trapping Conical Intersections.

    PubMed

    Saltiel, Jack; Redwood, Christopher E

    2016-05-12

    We report photoisomerization and photoaddition quantum yields in ethanol starting from each 1,4-diphenyl-1,3-butadiene, DPB, isomer. Despite the fact that the trans,trans isomer, tt-DPB, has a significant fluorescence quantum yield and lifetime, whereas no fluorescence is observed from the cis isomers, ether formation occurs with similar efficiency from tt-DPB and ct-DPB and less efficiently from cc-DPB. Photoaddition is about 72 times slower than photoisomerization to the ct- and tt-DPB isomers starting from tt- and ct-DPB, respectively. The results are consistent with addition of alcohol to the common zwitterionic trans-phenallyl cation/benzyl anion intermediate that leads to photoisomerization through a conical intersection. Ether formation from cc-DPB tracks inefficient formation of tt-DPB indicating that the small bicycle pedal cc-DPB → tt-DPB component proceeds stepwise through the same zwitterionic trans-phenallyl cation/benzyl anion intermediate. Previous results concerning the addition of methanol to the stilbenes are similarly interpreted. In contrast to trans-stilbene, the fluorescence and photoisomerization quantum yields of tt-DPB are inconsistent with the assumption of strict complementarity between radiative and torsional relaxation channels of tt-DPB in alcohols. PMID:27081783

  6. Crystal growth and characterization of new nonlinear optical chalcone derivative: 1-(4-Methoxyphenyl)-3-(3, 4-dimethoxyphenyl)-2-propen-1-one

    NASA Astrophysics Data System (ADS)

    Shettigar, Venkataraya; Patil, P. S.; Naveen, S.; Dharmaprakash, S. M.; Sridhar, M. A.; Shashidhara Prasad, J.

    2006-09-01

    Synthesis and single-crystal growth of a new organic nonlinear optical (NLO) material of chalcone derivative, 1-(4-methoxyphenyl)-3-(3, 4-dimethoxyphenyl)-2-propen-1-one (DMMC) by slow evaporation technique is reported. Good-quality single crystals of size 28 mm×7 mm×3 mm are grown for a period of 20 days and characterized by FT-IR and NMR studies. The grown crystal has been subjected to single-crystal X-ray diffraction technique and cell parameters of the crystal were determined. The title compound crystallizes in monoclinic system with a noncentrosymmetric space group P2 1, with unit cell parameters a=6.4090(4) Å, b=10.4950(10) Å, c=11.4820(12) Å, β=98.336(7)°, Z=2 and V=764.15(12) Å 3. The thermal stability of the crystal was determined from TGA/DTA curve. The grown crystals were characterized for their optical transmission and mechanical hardness. The second harmonic generation (SHG) efficiency of the crystals was obtained by classical powder technique using Nd:YAG laser and it is found to be 15 times that of urea. The laser damage threshold value has been determined using Q-switched Nd:YAG laser.

  7. Synthesis, antitumor evaluation and molecular docking studies of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives.

    PubMed

    Xu, Feng; Yang, Zhen-Zhen; Jiang, Jun-Rong; Pan, Wan-Gui; Yang, Xiao-le; Wu, Jian-Yong; Zhu, Yan; Wang, John; Shou, Qi-Yang; Wu, Han-Gui

    2016-07-01

    A series of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives have been synthesized and evaluated for their antitumor activities. These compounds exhibited potent antiproliferative activities against MCF-7, Bewo and HL-60 cells and c-Met kinase inhibitory activities. Three compounds were highly effective against MCF-7, Bewo and HL-60 cells with IC50 values in 1.09-2.24μM. Molecular docking was further performed to study the inhibitor-c-Met kinase interactions, and the results show that compound 4j was potently bound to the c-Met kinase with three hydrogen bonds. The further research on acute toxicity and in vivo antitumor activity of compound 4j to ICR (Institute of Cancer Research) mice were carried out, and found 4j with a certain toxicity but good efficacy in vivo. Based on the preliminary results, it is deduced that compound 4j with potent c-Met kinase inhibitory activity may be a potential anticancer agent. PMID:27184766

  8. 3-nitro-1,2,4-triazol-5-one, a less sensitive explosive

    DOEpatents

    Lee, Kien-Yin; Coburn, Michael D.

    1988-01-01

    A less sensitive explosive, 3-nitro-1,2,4-triazol-5-one. The compound 3-nitro-1,2,4-triazol-5-one (NTO) has a crystal density of 1.93 g/cm.sup.3 and calculated detonation velocity and pressure equivalent to those of RDX. It can be prepared in high yield from inexpensive starting materials in a safe synthesis. Results from initial small-scale sensitivity tests indicate that NTO is less sensitive than RDX and HMX in all respects. A 4.13 cm diameter, unconfined plate-dent test at 92% of crystal density gave the detonation pressure predicted for NTO by the BKW calculation.

  9. Epitaxial growth of (1 1 1)-oriented spinel CoCr2O4/Al2O3 heterostructures

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoran; Choudhury, D.; Cao, Yanwei; Middey, S.; Kareev, M.; Meyers, D.; Kim, J.-W.; Ryan, P.; Chakhalian, J.

    2015-02-01

    High quality (1 1 1)-oriented CoCr2O4/Al2O3 heterostructures were synthesized on the sapphire (0 0 0 1) single crystal substrates by pulsed laser deposition. The structural properties are demonstrated by in-situ reflection high energy electron diffraction, atomic force microscopy, X-ray reflectivity, and X-ray diffraction. X-ray photoemission spectroscopy confirms that the films possess the proper chemical stoichiometry. This work offers a pathway to fabricating spinel type artificial quasi-two-dimensional frustrated lattices by means of geometrical engineering.

  10. Numerical thermodynamic studies of classical gravitational collapse in 3+1 and 4+1 dimensions

    SciTech Connect

    Constantineau, Benjamin; Edery, Ariel

    2011-10-15

    Recent numerical work on the gravitational collapse of a five-dimemsional (5D) [4+1] Yang-Mills instanton has provided numerical evidence that the free energy F=E-TS=E/3 of a 5D Schwarzschild black hole of mass E can be obtained classically via the Lagrangian. Although there is no Hawking radiation, these numerical results suggest that the quantity TS has a classical meaning. We investigate this association for the physically relevant case of 3+1 dimensional collapse. We track numerically the negative of the total Lagrangian -L during the gravitational collapse of a massless scalar field to a Schwarzschild black hole in isotropic coordinates. We show that -L approaches the free energy F=E-TS=E/2 of a four-dimensional Schwarzschild black hole to within 5%. We also show that the matter contribution to the free energy tends towards zero so that the entropy at late stages of the collapse is gravitational in origin. The entropy S makes a negative contribution to the free energy and this feature is observed in our numerical simulation. There is a pronounced dip (negative contribution) in a thin slice just inside the event horizon precisely where the metric field is nonstationary. This is in accord with recent work suggesting black hole entropy is connected with the nonstationary phase space hidden behind the event horizon. We also obtain thermodynamic results for the 5D collapse of a massless scalar field which confirms that previous 5D results are universal and independent of the type of matter undergoing the collapse.

  11. Multicomponent domino reactions of hydrazinecarbodithioates: concise access to 3-substituted 5-thiol-1,3,4-thiadiazolines.

    PubMed

    Jia, Huihui; Feng, Huangdi; Sun, Zhihua

    2015-08-14

    Two classes of addition/cycloaddition cascade reactions of hydrazinecarbodithioate (1) have been developed under mild reaction conditions. Reaction of hydrazinecarbodithioate (1) with formaldehyde solution (2) and propiolic acid (3) gives 3-propargyl-5-thiol-2,3-dihydro-1,3,4-thiadiazoles (5) via a decarboxylative coupling/cycloaddition domino sequence. When propiolic acid (3) is switched to phenyl boronic acid (4), a petasis/cycloaddition domino reaction is instead observed, in which 3-benzyl-5-thiol-2,3-dihydro-1,3,4-thiadiazoles (6) are obtained. Both these reactions show a wide range of functional-group compatibility for propiolic acids and aryl boronic acids, and give the corresponding products in moderate to good yields. PMID:26153819

  12. Design, synthesis and biological evaluation of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1H-pyrazole-4-carboxamides as CDK1/Cdc2 inhibitors.

    PubMed

    Ganga Reddy, V; Srinivasa Reddy, T; Lakshma Nayak, V; Prasad, Budaganaboyina; Reddy, Adiyala Praveen; Ravikumar, A; Taj, Shaik; Kamal, Ahmed

    2016-10-21

    A series of new (N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives (8-35) were designed, synthesized and evaluated as CDK1/Cdc2 inhibitors. Biological evaluation assays indicated that compounds 16 and 27 showed the most potent growth inhibitory activity against human cancer cell lines (MIAPaCa-2, MCF-7 and HeLa) with GI50 values ranging from 0.13 to 0.7 μM, compared with the positive control nocodazole (0.81-0.95 μM). Flow cytometric analysis revealed that these compounds induce cell cycle arrest in the G2/M phase and Western blot analysis suggested that compound treatment resulted in reduction of CDK1 expression levels in MCF-7 cell line. Moreover, the apoptosis inducing effect of the compounds was studied using Hoechst staining, Rhodamine 123 staining (MMP), carboxy-DCFDA staining (ROS), Annexin V-FITC assay. Based on these studies, two compounds 16 and 27 have been identified as promising new molecules that have the potential to be developed as leads. PMID:27344493

  13. Synthesis of some novel heterocylic compounds derived from 2-[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetohydrazide and investigation of their lipase and α-glucosidase inhibition.

    PubMed

    Bekircan, Olcay; Ülker, Serdar; Menteşe, Emre

    2015-12-01

    In the present study, 2-[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetohydrazide (1) was used as starting compound for the synthesis of 2-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetyl}-4-thiosemicarbazides (2a-c) and 5-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-1,3,4-oxadiazole-2-thione (5). The cyclization of compounds 2a-c in the presence of NaOH resulted in the formation of 5-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones (3a-c). Aminomethylation of compounds 3a-c and 5 with formaldehyde and N-methyl/phenylpiperazine furnished Mannich bases (4a-f and 6a-b). The newly synthesized compounds were well-characterized by IR, (1)H NMR, (13)C NMR, elemental analysis and mass spectral studies. They were also screened for their lipase and α-glucosidase inhibition. Among the tested compound 2c (IC50 = 2.50 ± 0.50 µM) showed the best anti-lipase activity and compounds 2c (IC50 = 3.41 ± 0.16 µM) and 6a (IC50 = 4.36 ± 0.10 µM) showed the best anti-α-glucosidase activity. PMID:25640970

  14. Vicarious nucleophilic substitution to prepare 1,3-diamino-2,4,6-trinitrobenzene or 1,3,5-triamino-2,4,6-trinitrobenzene

    DOEpatents

    Mitchell, Alexander R.; Pagoria, Philip F.; Schmidt, Robert D.

    1996-01-01

    The present invention relates to a process to produce 1,3-diamino-2,4,6-trinitrobenzene (DATB) or 1,3,5-triamino-2,4,6,-trinitrobenzene (TATB) by: (a) reacting at ambient pressure and a temperature of between about 0.degree. and 50.degree. C. for between about 0.1 and 24 hr, a trinitroaromatic compound of structure V: ##STR1## wherein X, Y, and Z are each independently selected from --H, or --NH.sub.2, with the proviso that at least 1 or 2 of X, Y, and Z are hydrogen, with an amount effective to produce DATB or TATB of 1,1,1-trialkylhydrazinium halide wherein alkyl is selected from methyl, ethyl, propyl or butyl and halide is selected from chloride, bromide or iodide. in the presence of a strong base selected from sodium butoxide, potassium butoxide, potassium propoxide, sodium propoxide, sodium ethoxide, potassium ethoxide, sodium methoxide, potassium methoxide, and combinations thereof; in a solvent selected from the group consisting of methanol, ethanol, propanol, butanol, dimethylsulphoxide, N-methylpyrrolidone, hexamethylphosphoramide, dimethylformide, dimethylacetamide and mixtures thereof, provided that when alcohols are present primarily DATB and picramide is formed; and (b) isolating the DATB or TATB produced. DATB and TATB are useful specialty explosives. TATB is also used for the preparation of benzenehexamine, a starting material for the synthesis of novel materials (optical imaging devices, liquid crystals, ferromagnetic compounds).

  15. A facile and regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles using click chemistry

    EPA Science Inventory

    The reaction of α-tosyloxy ketones, sodium azide and terminal alkynes in presence of copper(I) in aqueous polyethylene glycol afforded regioselectively 1,4-disubstituted 1,2,3-triazoles in good yield at ambient temperature. The one-pot exclusive formation of 1,4-disubstituted 1,2...

  16. New Pyrazolo[1',5':1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones Fluoroderivatives as Human A1 Adenosine Receptor Ligands.

    PubMed

    Graziano, Alessia; Giovannoni, Maria Paola; Cilibrizzi, Agostino; Crocetti, Letizia; Piaz, Vittorio Dal; Vergelli, Claudia; Trincavelli, Maria Letizia; Martini, Claudia; Giacomelli, Chiara

    2012-09-01

    In this paper we report the synthesis and biological evaluation of a new series of pyrazolo[1',5':1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones as human A1 adenosine receptor ligands. The tricyclic scaffold was modified at position 6 and 9 by introducing small alkyl chains and substituted phenyls. The most interesting compounds showed Ki for A1 in the submicromolar range (0.105-0.244 µM) and the most interesting term (compound 4c) combined an appreciable affinity for A1 (Ki = 0.132 µM) with a good selectivity toward A2A (43% inhibition at 10 µM) and A3 (46% inhibition at 10 µM). PMID:24061322

  17. A series of substituted (2E)-3-(2-fluoro-4-phenoxyphenyl)-1-phenylprop-2-en-1-ones.

    PubMed

    Chopra, Deepak; Mohan, T P; Vishalakshi, B; Row, T N Guru

    2007-12-01

    In the molecular structures of a series of substituted chalcones, namely (2E)-3-(2-fluoro-4-phenoxyphenyl)-1-phenylprop-2-en-1-one, C21H15FO2, (I), (2E)-3-(2-fluoro-4-phenoxyphenyl)-1-(4-fluorophenyl)prop-2-en-1-one, C21H14F2O2, (II), (2E)-1-(4-chlorophenyl)-3-(2-fluoro-4-phenoxyphenyl)prop-2-en-1-one, C21H14ClFO2, (III), (2E)-3-(2-fluoro-4-phenoxyphenyl)-1-(4-methylphenyl)prop-2-en-1-one, C22H17FO2, (IV), and (2E)-3-(2-fluoro-4-phenoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one, C22H17FO3, (V), the configuration of the keto group with respect to the olefinic double bond is s-cis. The molecules pack utilizing weak C-H...O and C-H...pi intermolecular contacts. Identical packing motifs involving C-H...O interactions, forming both chains and dimers, along with C-H...pi dimers and pi-pi aromatic interactions are observed in the fluoro, chloro and methyl derivatives. PMID:18057618

  18. (2E)-3-(4-Fluoro­phen­yl)-1-[5-methyl-1-(4-methyl­phen­yl)-1H-1,2,3-triazol-4-yl]prop-2-en-1-one1

    PubMed Central

    Abdel-Wahab, Bakr F.; Mohamed, Hanan A.; Ng, Seik Weng; Tiekink, Edward R. T.

    2013-01-01

    With respect to the triazole ring in the title compound, C19H16FN3O, the p-tolyl ring is inclined [dihedral angle = 51.79 (11)°], whereas the chalcone residue is almost coplanar [O—C—C—N and C—C—C—C torsion angles = −178.71 (19) and 178.42 (18)°, respectively]. The conformation about the C=C bond [1.328 (3) Å] is E, and the triazole methyl group and the carbonyl O atom are syn. In the crystal, centrosymmetrically related mol­ecules are connected by π–π inter­actions between the triazole and p-tolyl rings [centroid–centroid distance = 3.6599 (12) Å] and these are linked into a three-dimensional architecture by C—H⋯N and C—H⋯π inter­actions. PMID:23723805

  19. 3,3′-(Piperazine-1,4-diium-1,4-di­yl)di­propionate dihydrate

    PubMed Central

    Jin, Shouwen; Huang, Yanfei; Fang, Hao; Wang, Tianyi; Ding, Liangliang

    2012-01-01

    During the recrystallization of 3-[4-(2-carb­oxy­eth­yl)piperazin-1-yl]propionic acid, the carb­oxy­lic acid H atoms were transferred to the piperazine N atoms, forming the title compound, C10H18N2O4·2H2O, in which the zwitterion lies about an inversion center. In the crystal, bifurcated N—H⋯(O,O) hydrogen bonds connect the zwitterions into a two-dimensional framework parallel to (-102) forming R 4 4(30) rings. O—H⋯O hydrogen bonds involving the solvent water mol­ecules connect the two-dimensional framework into a three-dimensional network. In addition, weak C—H⋯O hydrogen bonds are observed. PMID:23125633

  20. Design, synthesis and nonlinear optical properties of (E)-1-(4-substituted)-3-(4-hydroxy-3-nitrophenyl) prop-2-en-1-one compounds

    NASA Astrophysics Data System (ADS)

    Saha, Amrita; Shukla, Vijay; Choudhury, Sudip; Jayabalan, J.

    2016-06-01

    A new series of (E)-1-(4-substituted)-3-(4-hydroxy-3-nitrophenyl) prop-2-en-1-one compounds have been synthesized by Claisen-Schmidt condensation reaction. Nonlinear optical characterization were carried out using z-scan technique with nanosecond pulses. These samples are found to exhibit strong nonlinear absorption at 532 nm and the nonlinear absorption coefficient of these samples exponentially increases with the increase of phonon characteristic energy. This relation speaks the role of phonon in the origin of nonlinear absorption in these compounds. The reported dependence of optical nonlinearity of the chalcone derivatives on the phonon characteristic energy will help in designing similar class of new molecules with high nonlinear coefficients.

  1. 3-Substituted pyrazoles and 4-substituted triazoles as inhibitors of human 15-lipoxygenase-1.

    PubMed

    Pelcman, Benjamin; Sanin, Andrei; Nilsson, Peter; No, Kiyo; Schaal, Wesley; Öhrman, Sara; Krog-Jensen, Christian; Forsell, Pontus; Hallberg, Anders; Larhed, Mats; Boesen, Thomas; Kromann, Hasse; Vogensen, Stine Byskov; Groth, Thomas; Claesson, Hans-Erik

    2015-08-01

    Investigation of 1N-substituted pyrazole-3-carboxanilides as 15-lipoxygenase-1 (15-LOX-1) inhibitors demonstrated that the 1N-substituent was not essential for activity or selectivity. Additional halogen substituents on the pyrazole ring, however, increased activity. Further development led to triazole-4-carboxanilides and 2-(3-pyrazolyl) benzoxazoles, which are potent and selective 15-LOX-1 inhibitors. PMID:26037322

  2. Highly selective aldose reductase inhibitors. 3. Structural diversity of 3-(arylmethyl)-2,4,5-trioxoimidazolidine-1-acetic acids.

    PubMed

    Kotani, T; Nagaki, Y; Ishii, A; Konishi, Y; Yago, H; Suehiro, S; Okukado, N; Okamoto, K

    1997-02-28

    Accumulation of intracellular sorbitol, the reduced product of glucose, catalyzed by aldose reductase (AR) (EC 1.1.1.21), is thought to be the cause of the development of diabetic complications. Our attention is focused on finding compounds which inhibit AR without significantly inhibiting aldehyde reductase (ALR) (EC 1.1.1.2). The uracil or 2,4-dioxoimidazolidine skeleton having the benzothiazolyl or 4-chloro-3-nitrophenyl group as an aryl part indicated not only extremely high AR inhibitory activity but also AR selectivity. The ratio of IC50(ALR)/IC50(AR) of 3-[(5-chlorobenzothiazol-2-yl)methyl]-1,2,3,4-tetrahydro-2,4- dioxopyrimidine-1-acetic acid (47d) was more than 17 500. The uracil skeleton with the benzothiazolyl moiety seemed to be the best combination for selective AR inhibition. PMID:9057855

  3. Effects of 3-(3,4-dichlorophenyl)-1,1-dimethylurea on the cell cycle in Euglena gracilis

    SciTech Connect

    Yee, Muhching; Bartholomew, J.C. )

    1989-11-01

    The cell cycle of the photosynthetic unicellular alga Euglena gracilis growing in phototrophic medium is regulated by light. To investigate the relationship of this cell cycle response to light stimulated photosynthesis, we have tested the effect of the photosynthesis inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) on Euglena cell cycle transit. While DCMU does not block light stimulated cells from entering the S phase of the cell cycle, it does inhibit the transit through G{sub 2}/M. The specificity of this response and its relationship to photosynthesis was studied by looking at the effect of DCMU on dark grown wild-type cells, and on two bleached variants of Euglena (W{sub 3}BUL and W{sub 10}BSmL) that lack chloroplasts. The drug does block G{sub 2}/M in these cells, but not entrance into the cell cycle. Our studies show that entrance of cells into the cell cycle from a quiescent state does not require active photosynthesis, and that DCMU has effects on G{sub 2}/M transit that are independent of the photosynthetic capacity of the cells.

  4. Design, synthesis, structure-activity relationship and kinase inhibitory activity of substituted 3-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ones.

    PubMed

    Lamie, Phoebe F

    2016-07-01

    A new series of 3-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ones having variable substitutions at N5 and C6 positions has been synthesized and characterized. The synthesized compounds were tested for cytotoxicity against K562 and MCF-7 cancer cell lines and for inhibition of protein kinases CDK1/cyclin B, CDK2/cyclin E and Abl. Compounds 5f and 5h killed both K562 and MCF-7 cell lines with IC50 values 8.2, 9.6μM and 15.3, 10.8μM, respectively. In addition, 5f and 5h showed antiproliferative effect through arrest in G2/M phase on cell cycle of K562 cancer cell line in a dose-dependant manner. To confirm the mechanism of cell death, activity of caspase-3/7 was measured. Moreover, kinase selectivity profiling of the most potent compound 5f revealed several other sensitive targets, including RSK1 and RIPK2, TrkA and VEGFR. The results provide a starting point for optimization in order to increase their potency against kinases and cancer cell lines. PMID:27189674

  5. 40 CFR 721.7280 - 1,3-Propanediamine, N,N′-1,2-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.7280 1,3-Propanediamine,...

  6. Crystal structure of ( Z)-3-methyl-4-((naphth-1-ylamino)methylidene)-1-phenyl-1H-pyrazol-5(4H)-one

    NASA Astrophysics Data System (ADS)

    Sharma, N.; Parihar, S.; Jadeja, R. N.; Kant, R.; Gupta, V. K.

    2015-12-01

    The new pyrazolone derivative, ( Z)-3-methyl-4-((naphthalen-1-ylamino)methylidene)-1-phenyl-1H-pyrazol-5(4H)-one, C21H17N3O, is synthesized, and its crystal structure is determined by X-ray structure analysis. The crystals are orthorhombic, sp. gr. P212121, a = 6.5683(7), b = 12.7384(15), c = 20.198(3) Å, Z = 4, R = 0.0564 for 983 observed reflections. In crystal, the molecule exists in amine-one tautomeric form. The crystal structure is stabilized by N-H···O and C-H···O hydrogen bonds. In addition, C-H···π and π-π-interactions are observed.

  7. Discovery of Benzotriazolo[4,3-d][1,4]diazepines as Orally Active Inhibitors of BET Bromodomains.

    PubMed

    Taylor, Alexander M; Vaswani, Rishi G; Gehling, Victor S; Hewitt, Michael C; Leblanc, Yves; Audia, James E; Bellon, Steve; Cummings, Richard T; Côté, Alexandre; Harmange, Jean-Christophe; Jayaram, Hari; Joshi, Shivangi; Lora, Jose M; Mertz, Jennifer A; Neiss, Adrianne; Pardo, Eneida; Nasveschuk, Christopher G; Poy, Florence; Sandy, Peter; Setser, Jeremy W; Sims, Robert J; Tang, Yong; Albrecht, Brian K

    2016-02-11

    Inhibition of the bromodomains of the BET family, of which BRD4 is a member, has been shown to decrease myc and interleukin (IL) 6 in vivo, markers that are of therapeutic relevance to cancer and inflammatory disease, respectively. Herein we report substituted benzo[b]isoxazolo[4,5-d]azepines and benzotriazolo[4,3-d][1,4]diazepines as fragment-derived novel inhibitors of the bromodomain of BRD4. Compounds from these series were potent and selective in cells, and subsequent optimization of microsomal stability yielded representatives that demonstrated dose- and time-dependent reduction of plasma IL-6 in mice. PMID:26985289

  8. 7-endo selenocyclization reactions on chiral 3-prenyl and 3-cinnamyl-2-hydroxymethylperhydro-1,3-benzoxazine derivatives. A way to enantiopure 1,4-oxazepanes.

    PubMed

    Nieto, Javier; Andrés, Celia; Pérez-Encabo, Alfonso

    2015-09-14

    Enantiopure 1,4-oxazepane derivatives have been prepared by selenocyclofunctionalization of chiral 3-prenyl- and 3-cinnamyl-2-hydroxymethyl-substituted perhydro-1,3-benzoxazine derivatives. The 7-endo-cyclization occurs in high yields and diastereoselection. The regio- and stereochemistry of the cyclization products was dependent on the substitution pattern of the double bond, the nature of the hydroxyl group and the experimental conditions. PMID:26223944

  9. Vicarious nucleophilic substitution to prepare 1,3-diamino-2,4,6-trinitrobenzene or 1,3,5-triamino-2,4,6-trinitrobenzene

    DOEpatents

    Mitchell, A.R.; Pagoria, P.F.; Schmidt, R.D.

    1996-10-29

    The present invention relates to a process to produce 1,3-diamino-2,4,6-trinitrobenzene (DATB) or 1,3,5-triamino-2,4,6,trinitrobenzene (TATB) by: (a) reacting at ambient pressure and a temperature of between about 0 and 50 C for between about 0.1 and 24 hr, a trinitroaromatic compound of the structure shown within where X, Y, and Z are each independently selected from --H, or --NH{sub 2}, with the proviso that at least 1 or 2 of X, Y, and Z are hydrogen, with an amount effective to produce DATB or TATB, or 1,1,1-trialkylhydrazinium halide wherein alkyl is selected from methyl, ethyl, propyl or butyl and halide is selected from chloride, bromide or iodide, in the presence of a strong base selected from sodium butoxide, potassium butoxide, potassium propoxide, sodium propoxide, sodium ethoxide, potassium ethoxide, sodium methoxide, potassium methoxide, and combinations thereof; in a solvent selected from the group consisting of methanol, ethanol, propanol, butanol, dimethylsulfoxide, N-methylpyrrolidone, hexamethylphosphoramide, dimethylformide, dimethylacetamide and mixtures thereof, provided that when alcohols are present primarily DATB and picramide is formed; and (b) isolating the DATB or TATB produced. DATB and TATB are useful specialty explosives. TATB is also used for the preparation of benzenehexamine, a starting material for the synthesis of novel materials (optical imaging devices, liquid crystals, ferromagnetic compounds).

  10. Emission spectra of the cations of 1,3- and 1,4-dibromotetrafluorobenzene and of 1,3,5-tribromotrifluorobenzene in the gaseous phase

    USGS Publications Warehouse

    Maier, John Paul; Marthaler, O.; Mohraz, Manijeh; Shiley, R.H.

    1980-01-01

    A search was made for radiative decay of electronically excited cations of 24 bromobenzenes and of their fluoro-substituted derivatives in the gaseous phase. The only emission spectra detected were for the cations of 1,3- and 1,4-dibromotetrafluorobenzene and of 1,3,5-tribromotrifluorobenzene. The band systems, which are found between 670 and 830 nm, are assigned to the B(??-1) ??? A(??-1), X(??-1) electronic transitions of these cations. The assignments are based on the Ne(I) photoelectron spectra which are also presented for some of the studied species. The interpretation for the absence of detectable emission is that the nature of the B cationic states is ??-1, except in the case of 1,3- and 1,4-dibromobenzene cations for which B states are still formed by ??-1 processes. Possible reasons for these observations are discussed. The symmetries of the lowest three electronic states of the studied cations are given. ?? 1980.

  11. Reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithiethane with N-vinyl compounds

    PubMed Central

    Marshall, Will

    2013-01-01

    Summary The reaction of hexafluorothioacetone dimer (2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithiethane, 1) with vinylamides leads to the rapid formation of [2 + 2] cycloadducts: 4-amino-2,2-bis(trifluoromethyl)thietanes. The reaction proceeds in polar solvents (DMF, DMSO) in the absence of a catalyst at elevated temperature producing the corresponding cycloadducts in 47–86% yield. The reaction of N-vinylimidazole unexpectedly led to the formation of the corresponding 1-(hexafluoroisopropyl)-3-vinyl-1,3-dihydro-2H-imidazole-2-thione (5). The structure of this compound, along with the structures of two new thietanes was confirmed by single crystal X-ray diffraction. PMID:24367424

  12. Data describing the solution structure of the WW3* domain from human Nedd4-1.

    PubMed

    Panwalkar, Vineet; Schulte, Marianne; Lecher, Justin; Stoldt, Matthias; Willbold, Dieter; Dingley, Andrew J

    2016-09-01

    The third WW domain (WW3*) of human Nedd4-1 (Neuronal precursor cell expressed developmentally down-regulated gene 4-1) interacts with the poly-proline (PY) motifs of the human epithelial Na+ channel (hENaC) subunits at micromolar affinity. This data supplements the article (Panwalkar et al., 2015) [1]. We describe the NMR experiments used to solve the solution structure of the WW3* domain. We also present NOE network data for defining the rotameric state of side chains of peptide binding residues, and complement this data with χ 1 dihedral angles derived from (3) J couplings and molecular dynamics simulations data. PMID:27419198

  13. HAER DEL,3MILF.V,2 (sheet 1 of 4) Mispillion Lighthouse, South ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    HAER DEL,3-MILF.V,2- (sheet 1 of 4) - Mispillion Lighthouse, South bank of Mispillion River at its confluence with Delaware River at northeast end of County Road 203, 7 miles east of Milford, Milford, Sussex County, DE

  14. 3-amido-4-anilinocinnolines as a novel class of CSF-1R inhibitor.

    PubMed

    Scott, David A; Dakin, Les A; Del Valle, David J; Diebold, R Bruce; Drew, Lisa; Gero, Thomas W; Ogoe, Claude A; Omer, Charles A; Repik, Galina; Thakur, Kumar; Ye, Qing; Zheng, Xiaolan

    2011-03-01

    3-Amido-4-anilinocinnolines have been identified as potent and highly selective inhibitors of CSF-1R. The synthesis and SAR of these compounds is reported, along with some physical property, pharmacokinetic and kinase selectivity data. PMID:21295474

  15. 1. 3/4 view of N & W elevations, showing relationship ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. 3/4 view of N & W elevations, showing relationship to Building 140 at right; looking SE. - Rock Island Arsenal, Building No. 139, Second Street between Ramsey Street & South Avenue, Rock Island, Rock Island County, IL

  16. Studies on molecular structure, vibrational spectra and molecular docking analysis of 3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl 4-aminobenzoate

    NASA Astrophysics Data System (ADS)

    Suresh, D. M.; Amalanathan, M.; Hubert Joe, I.; Bena Jothy, V.; Diao, Yun-Peng

    2014-09-01

    The molecular structure, vibrational analysis and molecular docking analysis of the 3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl 4-aminobenzoate (MDDNAB) molecule have been carried out using FT-IR and FT-Raman spectroscopic techniques and DFT method. The equilibrium geometry, harmonic vibrational wave numbers, various bonding features have been computed using density functional method. The calculated molecular geometry has been compared with experimental data. The detailed interpretation of the vibrational spectra has been carried out by using VEDA program. The hyper-conjugative interactions and charge delocalization have been analyzed using natural bond orbital (NBO) analysis. The simulated FT-IR and FT-Raman spectra satisfactorily coincide with the experimental spectra. The PES and charge analysis have been made. The molecular docking was done to identify the binding energy and the Hydrogen bonding with the cancer protein molecule.

  17. Crystal engineering using bisphenols and trisphenols. Complexes with 1,10-phenanthroline: hydrogen-bonded chains in adducts with 4,4'-biphenol (1/1) and 4,4'-sulfonyldiphenol (2/3), pi-pi stacked chains in the (1/2) adduct with 4,4'-thiodiphenol, and pairwise-interwoven nets in 1,1,1-tris(4-hydroxyphenyl)ethane-1,10-phenanthroline-methanol (1/1/1).

    PubMed

    Ferguson; Glidewell; Lavender

    1999-08-01

    In 4,4'-biphenol-1,10-phenanthroline (1/1) [systematic name: 4,4'-biphenyldiol-1,10-phenanthroline (1/1)] the diphenol molecules lie across centres of inversion and the phenanthroline molecules lie across twofold rotation axes; the phenanthroline molecules act as chain-building units and the molecular components are linked into steeply zigzag C(16) chains parallel to [101] by means of O-H.N hydrogen bonds. In the structure of 4,4'-thiodiphenol-1,10-phenanthroline (1/2) the phenanthroline molecules act as chain-terminating units; the supramolecular aggregation is finite, with the bisphenol linked to each phenanthroline molecule by means of a single O-H.N hydrogen bond. pi-pi stacking interactions between the phenanthroline molecules in neighbouring hydrogen-bonded aggregates serve to link these aggregates into a continuous two-dimensional array. The phenanthroline molecules in 4,4'-sulfonyldiphenol-1,10-phenanthroline (2/3) play two roles: molecules in general positions act as chain-terminating units and are linked to the sulfonyldiphenol molecules by means of three-centre O-H.(N)(2) hydrogen bonds, while those lying across twofold rotation axes act as chain builders and are linked to two different sulfonyldiphenol molecules by means of a two-centre O-H.N hydrogen bond in each case; the resulting U-shaped five-component aggregates are further linked by C-H.O=S hydrogen bonds into a C(3)(3)(17)[R(2)(2)(12)] 'chain of rings' along [001]. In 1,1,1-tris(4-hydroxyphenyl)ethane-1,10-phenanthroline-methanol (1/1/1) [systematic name: 4,4',4"-ethylidynetriphenol-1,10-phenanthroline-methanol (1/1/1)] the phenanthroline molecules again act as chain-terminating units: the trisphenol molecules and the methanol molecules are linked by O-H.O hydrogen bonds into two-dimensional nets built from R(6)(6)(42) rings, and pairs of these nets are interwoven. The formation of each net utilizes two hydroxyl groups per trisphenol molecule as hydrogen-bond donors and the remaining hydroxyl

  18. 40 CFR 721.805 - Benzenamine, 4,4′-[1,3-phenylenebis(1-methylethyl idene)]bis[2,6-dimethyl-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... workplace. Requirements as specified in § 721.63 (a)(1), (a)(3), (a)(4), (a)(5)(iv) through (a)(5)(xv), (a)(6)(i), (a)(6)(ii), (b) (concentration set at 0.1 percent), and (c). (ii) Hazard communication... subject to reporting. (1) The chemical substance benzenamine, 4,4′- bis[2,6-dimethyl- (CAS Registry...

  19. r-1,t-2,3,c-4-Tetrahydroxy-1,2,3,4-tetrahydrophenanthrene in human urine: a potential biomarker for assessing polycyclic aromatic hydrocarbon metabolic activation.

    PubMed

    Hecht, Stephen S; Chen, Menglan; Yagi, Haruhiko; Jerina, Donald M; Carmella, Steven G

    2003-12-01

    Individual differences in the metabolic activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons (PAHs) may influence cancer risk. This has been investigated in many studies using genotyping approaches, but the results to date have been inconsistent. We propose that carcinogen metabolite phenotyping would be a more reliable way to determine the role of host metabolism in PAH-related cancer. Many PAHs are metabolically activated by formation of bay-region diol epoxides. Phenanthrene, generally considered to be noncarcinogenic, is the simplest PAH with a bay region and is metabolized to diol epoxides by the same enzymes and with the same stereochemistry as the prototypic carcinogenic PAH, benzo[a]pyrene. The major end product of this metabolic activation pathway is r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (trans, anti-PheT). We have developed a method for the analysis of trans, anti-PheT in human urine. r-1,t-2,4,c-3-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (trans, syn-PheT) was used as internal standard. After hydrolysis by beta-glucuronidase and sulfatase, solid phase extraction, and high-performance liquid chromatography collection, the sample was silylated and analyzed by gas chromatography-negative ion chemical ionization-mass spectrometry-selected ion monitoring at m/z 372. The resulting chromatograms were remarkably clean and trans, anti-PheT was readily detected in all human urine samples. Levels of trans, anti-PheT were 791 +/- 363 pmol/mg creatinine (n = 20) in psoriasis patients treated with a PAH-containing ointment, 25.7 +/- 16.8 pmol/mg creatinine (n = 32) in coke oven workers exposed to PAH, 4.58 +/- 2.95 pmol/mg creatinine (n = 31) in smokers, and 1.51 +/- 1.15 pmol/mg creatinine (n = 30) in nonsmokers. Levels of trans, anti-PheT correlated with levels of 1-hydroxypyrene in the urine of coke oven workers, smokers, and nonsmokers. Thus, trans, anti-PheT appears to be an excellent biomarker of PAH uptake. Levels

  20. Comparative integromics on FAT1, FAT2, FAT3 and FAT4.

    PubMed

    Katoh, Yuriko; Katoh, Masaru

    2006-09-01

    WNT5A, WNT5B, WNT11, FZD3, FZD6, VANGL1, VANGL2, DVL1, DVL2, DVL3, PRICKLE1, PRICKLE2, ANKRD6, NKD1, NKD2, DAAM1, DAAM2, CELSR1, CELSR2, CELSR3, ROR1 and ROR2 are planar cell polarity (PCP) signaling molecules implicated in the regulation of cellular polarity, convergent extension, and invasion. FAT1, FAT2, FAT3 and FAT4 are Cadherin superfamily members homologous to Drosophila Fat, functioning as a positive regulator of PCP in the Drosophila wing. Complete coding sequence (CDS) for human FAT1 (NM_005245.3) and FAT2 (NM_001447.1) are available, while artificial CDS for human FAT3 (XM_926199 and XM_936538) and partial CDS for FAT4 (NM_024582.2). Here, complete CDS of human FAT3 and FAT4 were determined by using bioinformatics and human intelligence (Humint). FAT3 gene, consisting of 26 exons, encoded a 4557-aa protein with extracellular 33 Cadherin repeats, one Laminin G (LamG) domain and two EGF domains. FAT4 gene encoded a 4924-aa protein with extracellular 34 Cadherin repeats, two LamG domains and three EGF domains. Cytoplasmic VCSVxPxLP and SDYxS motifs were identified as novel motifs conserved among FAT1, FAT2 and FAT3 orthologs. Domain architecture comparison and phylogenetic analysis revealed that FAT1, FAT2 and FAR3 were divergent from FAT4. FAT1-MTNR1A locus at 4q35.2 and FAT3-MTNR1B locus at 11q14.3-q21 were paralogous regions within the human genome. FAT1 mRNA was expressed in embryonic stem (ES) cells, neural tissues, gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, lung cancer and brain tumors. FAT2 mRNA was expressed in infant brain, cerebellum, gastric cancer, pancreatic cancer, ovarian cancer, esophageal cancer, skin squamous cell carcinoma, head and neck cancer. FAT3 mRNA was expressed in ES cells, primitive neuroectoderm, fetal brain, infant brain, adult neural tissues and prostate. FAT4 mRNA was expressed in fetal brain, infant brain, brain tumor and colorectal cancer. FAT family members were revealed to be targets of systems

  1. Synthesis and anti-inflammatory activity of 5-(6-methyl-2-substituted 4-pyrimidinyloxymethyl)-1,3,4-oxadiazole-2-thiones and their 3-morpholinomethyl derivatives.

    PubMed

    Jakubkiene, Virginija; Burbuliene, Milda Malvina; Mekuskiene, Giedrute; Udrenaite, Emilija; Gaidelis, Povilas; Vainilavicius, Povilas

    2003-04-01

    The synthesis of 5-(6-methyl-2-substituted 4-pyrimidinyloxymethyl)-2,3-dihydro-1,3,4-oxadiazole-2-thiones and their 3-morpholinomethyl derivatives and the results of anti-inflammatory activity in vivo are described. Most of the tested compounds exhibited anti-inflammatory activity and some of them were more active than acetylsalicylic acid. PMID:12727542

  2. RELEASE NOTES FOR MODELS-3 VERSION 4.1 PATCH: SMOKE TOOL AND FILE CONVERTER

    EPA Science Inventory

    This software patch to the Models-3 system corrects minor errors in the Models-3 framework, provides substantial improvements in the ASCII to I/O API format conversion of the File Converter utility, and new functionalities for the SMOKE Tool. Version 4.1 of the Models-3 system...

  3. Investigations on the synthesis and pharmacological properties of amides of 7-methyl-3-phenyl-1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-2,4- dioxo-1,2,3,4-tetrahydropyrido[2,3-d]-pyrimidine-5-carboxylic acid.

    PubMed

    Sladowska, H; Sieklucka-Dziuba, M; Rajtar, G; Sadowski, M; Kleinrok, Z

    1999-01-01

    Synthesis of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4- tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acid (6-10) and their 1-[2-hydroxy-3(4-phenyl-1-piperazinyl)propyl] derivatives (11-15) are described. Some of them displayed strong analgesic activity. PMID:10668178

  4. Agonist activity of a novel compound, 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554), at central 5-HT1A receptors.

    PubMed

    Matsuda, T; Seong, Y H; Aono, H; Kanda, T; Baba, A; Saito, K; Tobe, A; Iwata, H

    1989-10-24

    We used an in vitro radioligand receptor binding assay with rat cerebral cortex, hippocampus and striatum membrane preparations to show that 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554) had much higher affinity for 5-HT1A recognition sites than for 5-HT1-non-A, 5-HT2, benzodiazepine, dopamine D-2 and alpha 2-adrenergic recognition sites. The compound inhibited the activity of forskolin-stimulated adenylate cyclase in rat hippocampal membranes. Intraperitoneal injection of BP-554 to mice decreased the concentration of only 5-hydroxy-indoleacetic acid of the amines and their metabolites in the brain and decreased the accumulation of 5-hydroxytryptophan in the brain after decarboxylase inhibition by 3-hydroxybenzylhydrazine. Furthermore, the administration of BP-554 caused hypothermia and increased serum corticosterone levels in mice. The observed effects of BP-554 were similar to those of 8-hydroxy-2-(di-n-propylamino)tetralin. These results suggest that BP-554 acts as a selective 5-HT1A receptor agonist in vivo. PMID:2533078

  5. 3-(Piperidin-4-ylmethoxy)pyridine Containing Compounds Are Potent Inhibitors of Lysine Specific Demethylase 1.

    PubMed

    Wu, Fangrui; Zhou, Chao; Yao, Yuan; Wei, Liping; Feng, Zizhen; Deng, Lisheng; Song, Yongcheng

    2016-01-14

    Methylation of histone lysine residues plays important roles in gene expression regulation as well as cancer initiation. Lysine specific demethylase 1 (LSD1) is responsible for maintaining balanced methylation levels at histone H3 lysine 4 (H3K4). LSD1 is a drug target for certain cancers, due to important functions of methylated H3K4 or LSD1 overexpression. We report the design, synthesis, and structure-activity relationships of 3-(piperidin-4-ylmethoxy)pyridine containing compounds as potent LSD1 inhibitors with Ki values as low as 29 nM. These compounds exhibited high selectivity (>160×) against related monoamine oxidase A and B. Enzyme kinetics and docking studies suggested they are competitive inhibitors against a dimethylated H3K4 substrate and provided a possible binding mode. The potent LSD1 inhibitors can increase cellular H3K4 methylation and strongly inhibit proliferation of several leukemia and solid tumor cells with EC50 values as low as 280 nM, while they had negligible effects on normal cells. PMID:26652247

  6. Dynamic Histone Acetylation of H3K4me3 Nucleosome Regulates MCL1 Pre-mRNA Splicing.

    PubMed

    Khan, Dilshad H; Gonzalez, Carolina; Tailor, Nikesh; Hamedani, Mohammad K; Leygue, Etienne; Davie, James R

    2016-10-01

    Pre-mRNA splicing is a cotranscriptional process affected by the chromatin architecture along the body of coding genes. Recruited to the pre-mRNA by splicing factors, histone deacetylases (HDACs) and K-acetyltransferases (KATs) catalyze dynamic histone acetylation along the gene. In colon carcinoma HCT 116 cells, HDAC inhibition specifically increased KAT2B occupancy as well as H3 and H4 acetylation of the H3K4 trimethylated (H3K4me3) nucleosome positioned over alternative exon 2 of the MCL1 gene, an event paralleled with the exclusion of exon 2. These results were reproduced in MDA-MB-231, but not in MCF7 breast adenocarcinoma cells. These later cells have much higher levels of demethylase KDM5B than either HCT 116 or MDA-MB-231 cells. We show that H3K4me3 steady-state levels and H3K4me3 occupancy at the end of exon 1 and over exon 2 of the MCL1 gene were lower in MCF7 than in MDA-MB-231 cells. Furthermore, in MCF7 cells, there was minimal effect of HDAC inhibition on H3/H4 acetylation and H3K4me3 levels along the MCL1 gene and no change in pre-mRNA splicing choice. These results show that, upon HDAC inhibition, the H3K4me3 mark plays a critical role in the exclusion of exon 2 from the MCL1 pre-mRNA. J. Cell. Physiol. 231: 2196-2204, 2016. © 2016 Wiley Periodicals, Inc. PMID:26864447

  7. Ubiquitin E3 ligase FIEL1 regulates fibrotic lung injury through SUMO-E3 ligase PIAS4.

    PubMed

    Lear, Travis; McKelvey, Alison C; Rajbhandari, Shristi; Dunn, Sarah R; Coon, Tiffany A; Connelly, William; Zhao, Joe Y; Kass, Daniel J; Zhang, Yingze; Liu, Yuan; Chen, Bill B

    2016-05-30

    The E3 small ubiquitin-like modifier (SUMO) protein ligase protein inhibitor of activated STAT 4 (PIAS4) is a pivotal protein in regulating the TGFβ pathway. In this study, we discovered a new protein isoform encoded by KIAA0317, termed fibrosis-inducing E3 ligase 1 (FIEL1), which potently stimulates the TGFβ signaling pathway through the site-specific ubiquitination of PIAS4. FIEL1 targets PIAS4 using a double locking mechanism that is facilitated by the kinases PKCζ and GSK3β. Specifically, PKCζ phosphorylation of PIAS4 and GSK3β phosphorylation of FIEL1 are both essential for the degradation of PIAS4. FIEL1 protein is highly expressed in lung tissues from patients with idiopathic pulmonary fibrosis (IPF), whereas PIAS4 protein levels are significantly reduced. FIEL1 overexpression significantly increases fibrosis in a bleomycin murine model, whereas FIEL1 knockdown attenuates fibrotic conditions. Further, we developed a first-in-class small molecule inhibitor toward FIEL1 that is highly effective in ameliorating fibrosis in mice. This study provides a basis for IPF therapeutic intervention by modulating PIAS4 protein abundance. PMID:27162139

  8. Magnetoelectric and magnetic properties of aluminum borates Ho1 - x Nd x Al3(BO3)4

    NASA Astrophysics Data System (ADS)

    Volkov, N. V.; Gudim, I. A.; Demidov, A. A.; Eremin, E. V.

    2015-03-01

    The magnetoelectric and magnetic properties of substituted aluminum borates Ho1 - x Nd x Al3(BO3)4 have been studied experimentally and theoretically. A large magnetoelectric effect exceeding all known values in isostructural compounds except for HoAl3(BO3)4 has been found. The magnetoelectric polarization of Ho0.8Nd0.2Al3(BO3)4 and Ho0.5Nd0.5Al3(BO3)4 at T = 5 K in a field of 9 T is Δ P ab ( B b ) ≈ -2630 and 1380 μC/m2, respectively. A theoretical consideration based on the crystal field model for the rare-earth ion made it possible to interpret all measured properties within the unified approach. The crystal field parameters have been determined. The temperature (3-300 K) and field (up to 9 T) dependences of the magnetization and the temperature (5-100 K) and field (up to 9 T) dependences of the polarization have been described. The studied properties of Ho1 - x Nd x Al3(BO3)4 have been compared with those of HoAl3(BO3)4 demonstrating record-high polarization values.

  9. Analysis and Characterization of 3-(3,4-Dichlorophenyl)-1,1-Dimethylurea (DCMU)-resistant Euglena

    PubMed Central

    Calvayrac, Régis; Bomsel, Jean-Loup; Laval-Martin, Danielle

    1979-01-01

    Cultures of Euglena gracilis Klebs strain Z Pringsheim were grown photoorganotrophically in the presence of different concentrations of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) in the range of 0.05 to 250 micromolar. Cultures were serially transferred and various metabolic parameters were followed for 10 weeks. A process of adaptation occurred which was divided operationally into three phases. A phase of ultrastructural disorganization occurred, succeeded by a recovery phase; their intensity and duration were functions of the dose of DCMU. A stable adaptation phase then ensued. This phase was observed in all cultures except that exposed to the highest DCMU concentration. Adapted cells from all of the DCMU cultures contained twice the protein and half the paramylon of the control cells and thus utilized the carbon source to accumulate cellular reserves with only half the efficiency of controls. DCMU affected cellular metabolism as well as photosynthesis. The energy charge remained at high levels throughout adaptation, although the size of the adenylate pool was half that of controls at the disorganized phase. At this stage the ultrastructure of chloroplasts and mitochondria was considerably modified. The progressive changes of the parameters studied appeared to affect all of the cells in a given culture. Images PMID:16660827

  10. Zn(II) and Cu(II) complexes generated from 5-(pyridin-4-yl)-3-[2-(pyridin-4-yl)ethyl]-1,3,4-oxadiazole-2(3H)-thione.

    PubMed

    Zhao, Hang-Ju; Ma, Jian-Ping; Liu, Qi-Kui; Dong, Yu-Bin

    2013-07-01

    A new 1,3,4-oxadiazole-containing bispyridyl ligand, namely 5-(pyridin-4-yl)-3-[2-(pyridin-4-yl)ethyl]-1,3,4-oxadiazole-2(3H)-thione (L), has been used to create the novel complexes tetranitratobis{μ-5-(pyridin-4-yl)-3-[2-(pyridin-4-yl)ethyl]-1,3,4-oxadiazole-2(3H)-thione}zinc(II), [Zn2(NO3)4(C14H12N4OS)2], (I), and catena-poly[[[dinitratocopper(II)]-bis{μ-5-(pyridin-4-yl)-3-[2-(pyridin-4-yl)ethyl]-1,3,4-oxadiazole-2(3H)-thione}] nitrate acetonitrile sesquisolvate dichloromethane sesquisolvate], {[Cu(NO3)(C14H12N4OS)2]NO3·1.5CH3CN·1.5CH2Cl2}n, (II). Compound (I) presents a distorted rectangular centrosymmetric Zn2L2 ring (dimensions 9.56 × 7.06 Å), where each Zn(II) centre lies in a {ZnN2O4} coordination environment. These binuclear zinc metallocycles are linked into a two-dimensional network through nonclassical C-H···O hydrogen bonds. The resulting sheets lie parallel to the ac plane. Compound (II), which crystallizes as a nonmerohedral twin, is a coordination polymer with double chains of Cu(II) centres linked by bridging L ligands, propagating parallel to the crystallographic a axis. The Cu(II) centres adopt a distorted square-pyramidal CuN4O coordination environment with apical O atoms. The chains in (II) are interlinked via two kinds of π-π stacking interactions along [0-11]. In addition, the structure of (II) contains channels parallel to the crystallographic a direction. The guest components in these channels consist of dichloromethane and acetonitrile solvent molecules and uncoordinated nitrate anions. PMID:23832028

  11. [Overexpressing 3-ketosteroid-Δ1-dehydrogenase for degrading phytosterols into androst-1,4-diene-3,17-dione].

    PubMed

    Zhang, Lele; Zhang, Xian; Shao, Minglong; Chen, Rongrong; Rao, Zhiming; Li, Hu; Xu, Zhenghong

    2015-11-01

    We constructed plasmid pMTac to overexpress 3-ketosteroid-Δ1-dehydrogenase (KSDD) in Mycobacterium neoaurum JC-12 for improving androst-1,4-diene-3,17-dione (ADD) production. To construct pMTac, pACE promoter on pMF41 was replaced by tac promoter, and then four recombinants were constructed, which were M. neoaurum JC-12/pMF41-gfp, M. neoaurum JC-12/pMTac-gfp, M. neoaurum JC-12/pMF41-ksdd and M. neoaurum JC-12/pMTac-ksdd. Fluorescence detection results show that much more green fluorescent protein (GFP) was expressed in M. neoaurum JC-12/pMTac-ksdd than M. neoaurum JC-12/pMF41-ksdd. The activity of KSDD was 2.41 U/mg in M. neoaurum JC-12/pMTac-ksdd, 6.53-fold as that of M. neoaurum JC-12 and 4.36-fold as that of M. neoaurum JC-12/pMF41-ksdd. In shake flask fermentation, ADD production of M. neoaurum JC-12/pMTac-ksdd was 5.94 g/L, increased about 22.2% compared to the original strain M. neoaurum JC-12 and 12.7% to M. neoaurum JC-12/pMF41-ksdd. AD (4-androstene-3,17-dione) production of JC-12/pMTac-ksdd was 0.17 g/L, decreased 81.5% compared to M. neoaurum JC-12 and 71.2% to M neoaurum JC-12/pMF41-ksdd. In the 5 L fermenter, 20 g/L phytosterols was used as substrate, ADD production of M. neoaurum JC-12/pMTac-ksdd was improved to 10.28 g/L. pMTac is favorable for expressing KSDD in M. neoaurum JC-12, and overexpression of KSDD has beneficial effect on ADD producing, and it is the highest level ever reported using fermentation method in M. neoaurum. PMID:26939442

  12. Synthesis, structural, conformational and pharmacological study of some amides derived from 3 -methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9α-amine

    NASA Astrophysics Data System (ADS)

    Iriepa, I.; Bellanato, J.; Gálvez, E.; Gil-Alberdi, B.

    2010-07-01

    Some mono-substituted amides ( 2- 5) derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9α-amine were synthesized and studied by IR, 1H and 13C NMR spectroscopy. The crystal structure of 3-methyl-2,4-diphenyl-9α-(3,5-dichlorobenzamido)-3-azabicyclo[3.3.1]nonane ( 3) was determined by X-ray diffraction. NMR data showed that all compounds adopt in CDCl 3 a preferred flattened chair-chair conformation with the N-CH 3 group in equatorial disposition. X-ray data agreed with this conformation in the case of compound 3. IR data revealed that compounds 2 and 3 present a C dbnd O⋯HN intermolecular bond in the solid state. This conclusion was also confirmed by X-ray data of compound 3. In the case of compound 5, IR results suggested intermolecular NH⋯N-heterocyclic bonding. On the contrary, in the pyrazine derivative ( 4), IR, 1H and 13C NMR data showed the presence of an intramolecular NH⋯N1″-heterocyclic hydrogen bond in the solid state and solution. Moreover, NMR and IR data showed a preferred trans disposition for the NH-C dbnd O group. NMR also revealed free rotation of the -NH-CO-R group around C9-NH bond. Pharmacological assays on mice were drawn to evaluate analgesic activity.

  13. A food-grade industrial arming yeast expressing β-1,3-1,4-glucanase with enhanced thermal stability*

    PubMed Central

    Guo, Qin; Zhang, Wei; Ma, Liu-liu; Chen, Qi-he; Chen, Ji-cheng; Zhang, Hong-bo; Ruan, Hui; He, Guo-qing

    2010-01-01

    The aim of this work was to construct a novel food-grade industrial arming yeast displaying β-1,3-1,4-glucanase and to evaluate the thermal stability of the glucanase for practical application. For this purpose, a bi-directional vector containing galactokinase (GAL1) and phosphoglycerate kinase 1 (PGK1) promoters in different orientations was constructed. The β-1,3-1,4-glucanase gene from Bacillus subtilis was fused to α-agglutinin and expressed under the control of the GAL1 promoter. α-galactosidase induced by the constitutive PGK1 promoter was used as a food-grade selection marker. The feasibility of the α-galactosidase marker was confirmed by the growth of transformants harboring the constructed vector on a medium containing melibiose as a sole carbon source, and by the clear halo around the transformants in Congo-red plates owing to the expression of β-1,3-1,4-glucanase. The analysis of β-1,3-1,4-glucanase activity in cell pellets and in the supernatant of the recombinant yeast strain revealed that β-1,3-1,4-glucanase was successfully displayed on the cell surface of the yeast. The displayed β-1,3-1,4-glucanase activity in the recombinant yeast cells increased immediately after the addition of galactose and reached 45.1 U/ml after 32-h induction. The thermal stability of β-1,3-1,4-glucanase displayed in the recombinant yeast cells was enhanced compared with the free enzyme. These results suggest that the constructed food-grade yeast has the potential to improve the brewing properties of beer. PMID:20043351

  14. Crystal structure of methyl 3-(3-fluoro-phen-yl)-1-methyl-1,3a,4,9b-tetra-hydro-3H-thio-chromeno[4,3-c]isoxazole-3a-carboxyl-ate.

    PubMed

    Savithri, M P; Suresh, M; Raghunathan, R; Vimala, G; SubbiahPandi, A

    2015-08-01

    In the title compound, C19H18FNO3S, the five-membered oxazolidine ring adopts an envelope conformation with the methine C atom of the fused bond as the flap. Its mean plane is oriented at a dihedral angle of 50.38 (1)° with respect to the fluoro-phenyl ring. The six-membered thio-pyran ring has a half-chair conformation and its mean plane is almost coplanar with the fused benzene ring, making a dihedral angle of 4.94 (10)°. The two aromatic rings are inclined to one another by 85.96 (11)°, and the mean planes of the oxazolidine and thio-pyran rings are inclined to one another by 57.64 (12)°. In the crystal, mol-ecules are linked by C-H⋯π inter-actions, forming a three-dimensional structure. PMID:26396818

  15. Synthesis of 5-chloro-4,5-diaryl-. delta. /sup 3/-1,3-oxazolin-2-ones

    SciTech Connect

    Bal'on, Ya.G.; Smirnov, V.A.

    1987-09-20

    During an attempt at the synthesis of the oxazoles by the reactions of the oxazolines (I) with phosphorus pentachloride the authors obtained the 5-chloro-4,5-diaryl-..delta../sup 3/-1,3-oxazolin-2-ones instead of the expected 4,5-diaryl-2-chlorooxazoles. As electrophiles, these compounds are active in nucleophilic addition and substitution reactions. Thus, in their reaction with methanol the 4,5-dimethoxy-4,5-diaryl-1,3-oxazolidin-2-ones are formed with quantitative yields. When heated they are easily converted into 5-methoxy-4,5-diaryl-..delta..-1,3-oxazolin-2-ones. The compositions and structures were proved by IR and PMR spectroscopy and elemental analysis.

  16. 6,7-Dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinolines as superior reversal agents for P-glycoprotein-mediated multidrug resistance.

    PubMed

    Liu, Baomin; Qiu, Qianqian; Zhao, Tianxiao; Jiao, Lei; Li, Yunman; Huang, Wenlong; Qian, Hai

    2015-02-01

    P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle for successful cancer chemotherapy. Based on our previous study, 17 novel compounds with the 6,7-dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinoline scaffold were designed and synthesized. Among them, 2-[(1-{4-[2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl]phenyl}-1H-1,2,3-triazol-4-yl)methoxy]-N-(p-tolyl)benzamide (compound 7 h) was identified as a potent modulator of P-gp-mediated MDR, with high potency (EC50 =127.5 ± 9.1 nM), low cytotoxicity (TI>784.3), and long duration (>24 h) in reversing doxorubicin (DOX) resistance in K562/A02 cells. Compound 7 h also enhanced the effects of other MDR-related cytotoxic agents (paclitaxel, vinblastine, and daunorubicin), increased the accumulation of DOX and blocked P-gp-mediated rhodamine 123 efflux function in K562/A02 MDR cells. Moreover, 7 h did not have any effect on cytochrome (CYP3A4) activity. These results indicate that 7 h is a relatively safe modulator of P-gp-mediated MDR that has good potential for further development. PMID:25470220

  17. 1,3,4-Oxadiazole Derivatives. Optical Properties in Pure and Mixed Solvents.

    PubMed

    Homocianu, Mihaela; Airinei, Anton

    2016-09-01

    1,3,4-Oxadiazole derivatives-organic materials are an interesting and continuously developing area of research. This review describes some optical properties and highlights the current applications of these compounds in biomedical and optoelectronic fields. The relationships between polymer structures, environmental factors and optical properties (absorption and fluorescence) of several selected and relevant l,3,4-oxadiazole-containing molecules were presented in this review. These aspects were analyzed in various pure solvents and microheterogeneous media (mixed solvents). Also, the selectivity and sensitivity of some 1,3,4-oxadiazole derivatives-organic materials for different metal ions were discussed and evaluated by using spectral techniques. Finally, some important photophysical characteristics of 34 series of organic materials containing -1,3,4-oxadiazole rings, were collected in a table. PMID:27324952

  18. (E)-4-(3,4-Dimethoxyphenyl)but-3-en-1-ol Enhances Melanogenesis through Increasing Upstream Stimulating Factor-1-Mediated Tyrosinase Expression

    PubMed Central

    Bang, Seung Hyun; Han, Ah-Reum; Seo, Eun-Kyoung; Chang, Sung Eun; Kang, Duk-Hee; Oh, Eok-Soo

    2015-01-01

    We investigated the potential melanogenic effect of compounds from Zingiber cassumunar Roxb. Our data revealed that chloroform-soluble extract of Z. cassumunar enhanced melanin synthesis in B16F10 melanoma cells. Among the components of the chloroform extract, (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-ol (DMPB) increased melanogenesis in both B16F10 cells and human primary melanocytes. In B16F10 cells, DMPB enhanced the activation of ERK and p38, and the level of tyrosinase. Although the level of microphthalmia-associated transcription factor was unchanged in DMPB-treated B16F10 cells, DMPB increased levels and nuclear localization of upstream stimulating factor-1 (USF1). Consistently, DMPB-mediated melanin synthesis was diminished in USF1-knockdown cells. Furthermore, DMPB induced hyperpigmentation in brown guinea pigs in vivo. Together, these data suggest that DMPB may promote melanin synthesis via USF1 dependent fashion and could be used as a clinical therapeutic agent against hypopigmentation-associated diseases. PMID:26535571

  19. Membrane pore architecture of the CslF6 protein controls (1-3,1-4)-β-glucan structure

    PubMed Central

    Jobling, Stephen A.

    2015-01-01

    The cereal cell wall polysaccharide (1-3,1-4)-β-glucan is a linear polymer of glucose containing both β1-3 and β1-4 bonds. The structure of (1-3,1-4)-β-glucan varies between different cereals and during plant growth and development, but little is known about how this is controlled. The cellulose synthase–like CslF6 protein is an integral membrane protein and a major component of the (1-3,1-4)-β-glucan synthase. I show that a single amino acid within the predicted transmembrane pore domain of CslF6 controls (1-3,1-4)-β-glucan structure. A new mechanism for the control of the polysaccharide structure is proposed where membrane pore architecture and the translocation of the growing polysaccharide across the membrane control how the acceptor glucan is coordinated at the active site and thus the proportion of β1-3 and β1-4 bonds within the polysaccharide. PMID:26601199

  20. Synthesis, characterization and intramolecular proton transfer of 3,3";-dihydroxy-4,4";-[5-methyl-1,3-phenylenebis(nitrilomethylidyne)]-bis-phenol

    NASA Astrophysics Data System (ADS)

    Eshtiagh-Hosseini, Hossein; Beyramabadi, S. Ali; Morsali, Ali; Mirzaei, Masoud; Chegini, Hamed; Elahi, Morteza; Naseri, Mohammad Ali

    2014-08-01

    A newly synthesized Schiff base, 3,3";-dihydroxy-4,4";-[5-methyl-1,3-phenylenebis(nitrilomethylidyne)]-bis-phenol, was characterized experimentally. Its geometries optimization, tautomerization, assignment of the IR bands and NMR chemical shifts were calculated by using density functional theory (DFT) method. In addition, the atoms in molecules (AIM) analysis was employed for investigation of its tautomerization. Four possible tautomers of the investigated Schiff base were optimized in both of the gas and solution phases. The Schiff base has no planar structure, but each of the benzene rings is in a separate plane. In the most stable tautomer, the phenolic protons of the two sbnd OH groups are engaged in the intramolecular-hydrogen bond with the azomethine nitrogens. Good consistency between the theoretical and experimental results confirms validity of the optimized geometry. Also, kinetics and mechanism of the intramolecular-proton transfer of the studied Schiff base was demonstrated theoretically.

  1. Aryl-1,3,5-triazine derivatives as histamine H4 receptor ligands.

    PubMed

    Łażewska, Dorota; Więcek, Małgorzata; Ner, Joanna; Kamińska, Katarzyna; Kottke, Tim; Schwed, J Stephan; Zygmunt, Małgorzata; Karcz, Tadeusz; Olejarz, Agnieszka; Kuder, Kamil; Latacz, Gniewomir; Grosicki, Marek; Sapa, Jacek; Karolak-Wojciechowska, Janina; Stark, Holger; Kieć-Kononowicz, Katarzyna

    2014-08-18

    A series of novel 2-amino-4-(4-methylpiperazin-1-yl)-1,3,5-triazine derivatives with different aryl substituents in the 6-position was designed, synthesized and evaluated for histamine H4 receptor (H4R) affinity in Sf9 cells expressing human H4R co-expressed with G-protein subunits. Triazine derivative 8 with a 6-(p-chlorophenyl) substituent showed the highest affinity with hH4R Ki value of 203 nM and was classified as an antagonist in cAMP accumulation assay. This compound, identified as a new lead structure, demonstrated also anti-inflammatory properties in preliminary studies in mice (carrageenan-induced edema test) and neither possessed significant antiproliferative activity, nor modulated CYP3A4 activity up to concentration of 25 μM. In order to discuss structure-activity relationships molecular modeling and docking studies were undertaken. PMID:24996140

  2. 5-Phenyl-3-(2-thien­yl)-1,2,4-triazolo[3,4-a]isoquinoline

    PubMed Central

    Khan, F. Nawaz; Manivel, P.; Prabakaran, K.; Hathwar, Venkatesha R.; Ng, Seik Weng

    2010-01-01

    In the title mol­ecule, C20H13N3S, the triazoloisoquinoline ring system is approximately planar, with an r.m.s. deviation of 0.045 Å and a maximum deviation of 0.090 (2) Å from the mean plane for the triazole ring C atom which is bonded to the thio­phene ring. The phenyl ring is twisted by 52.0 (1)° with respect to the mean plane of the triazoloisoquinoline ring system. The thio­phene ring is rotationally disordered by approximately 180° over two sites, the ratio of refined occupancies being 0.73 (1):0.27 (1). PMID:21579895

  3. Biosynthesis of the Halogenated Auxin, 4-Chloroindole-3-Acetic Acid1[W][OA

    PubMed Central

    Tivendale, Nathan D.; Davidson, Sandra E.; Davies, Noel W.; Smith, Jason A.; Dalmais, Marion; Bendahmane, Abdelhafid I.; Quittenden, Laura J.; Sutton, Lily; Bala, Raj K.; Le Signor, Christine; Thompson, Richard; Horne, James; Reid, James B.; Ross, John J.

    2012-01-01

    Seeds of several agriculturally important legumes are rich sources of the only halogenated plant hormone, 4-chloroindole-3-acetic acid. However, the biosynthesis of this auxin is poorly understood. Here, we show that in pea (Pisum sativum) seeds, 4-chloroindole-3-acetic acid is synthesized via the novel intermediate 4-chloroindole-3-pyruvic acid, which is produced from 4-chlorotryptophan by two aminotransferases, TRYPTOPHAN AMINOTRANSFERASE RELATED1 and TRYPTOPHAN AMINOTRANSFERASE RELATED2. We characterize a tar2 mutant, obtained by Targeting Induced Local Lesions in Genomes, the seeds of which contain dramatically reduced 4-chloroindole-3-acetic acid levels as they mature. We also show that the widespread auxin, indole-3-acetic acid, is synthesized by a parallel pathway in pea. PMID:22573801

  4. The v4 = 1 and v4 = 2 rovibrational levels of PF3 revisited: New solutions for old topics

    NASA Astrophysics Data System (ADS)

    Ceausu-Velcescu, Adina; Pracna, Petr; Breidung, Jürgen; Thiel, Walter; Badaoui, Mohamed

    2015-10-01

    The high-resolution infrared spectra of trifluorophosphine (PF3) were reinvestigated in the ν4 fundamental region near 350 cm-1, and around 690 cm-1, with the aim to provide a necessary reassignment of the 2±2 sublevel of the v4 = 2 overtone level. The present paper reports on the first complete study of both sublevels of v4 = 2 (of A1 and E symmetry, corresponding to l4 = 0 and ±2, respectively), through the high-resolution analysis of the overtone 2 ν40 band and the 2 ν4±2 - ν4±1 hot band. The assignments of the latter were corrected and extended, spanning the rotational states J ⩽ 82 and -80 ⩽ K″ · ΔK ⩽ 48. These new infrared assignments in the v4 = 2 state were combined with accurate infrared, radiofrequency, centimeter-, millimeter- and submillimeter-wave data of the v4 = 1 level (Thiessen et al., 2000), together with rotational data in the ground vibrational state (Cotti et al., 1995), in a simultaneous fit. The existence of resonance crossings due to a Δk = ±1, Δl = ∓2 l-type resonance in the v4 = 1 state, which generated perturbation-allowed transitions, provided independent values of the C4 and Cζ4 constants. Combining these rotational transitions with the wavenumbers of the ν4 fundamental band enabled us to determine accurately the C0 axial ground state constant. Moreover, the assignment of a few, very weak rRK transitions in the 2 ν4-2 overtone band and their inclusion in the global least-squares fit allowed also the first accurate experimental determination of DK0. The obtained results are (in cm-1): C0 = 0.159970241(29) and DK0 =1.80457(49) × 10-7. Quadratic, cubic, and semidiagonal quartic force fields of PF3 have been calculated at the CCSD(T) level of theory employing a variety of large correlation-consistent basis sets. These force fields have been used to evaluate spectroscopic constants which are generally found to be in very good agreement with experiment. The present best estimate of the re structure of PF3 based on

  5. cis-1,3,4,6-Tetranitrooctahydroimidazo-[4,5-d]imidazole (BCHMX), its properties and initiation reactivity.

    PubMed

    Klasovitý, Dusan; Zeman, Svatopluk; Růzicka, Ales; Jungová, Marcela; Rohác, Michal

    2009-05-30

    Using the (15)N NMR chemical shifts of nitrogen atoms in nitramino groups of cis-1,3,4,6-tetranitrooctahydroimidazo-[4,5-d]imidazole (bicyclo-HMX or BCHMX) and additional 10 nitramines, we have assessed its reactivity in detonation, under the influence of impact, and by action of electric spark. It is stated that the thermal stability of BCHMX is higher than that of 1,3,5-trinitro-1,3,5-triazinane (RDX). The longest NN bond in the BCHMX molecule (1.412(4)A) is the cause for its higher impact reactivity, which is at the level of that of penterythritol tetranitrate (PETN). In the experimentally determined detonation velocity, BCMX can be slightly better performing than RDX. From the standpoint of friction sensitivity, BCHMX is similar to 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX). Attention was also focused on the solubility-temperature dependence of BCHMX in acetone, acetonitrile, ethyl acetate, dimethyl sulfoxide, tetrahydrofurane, and nitromethane. X-ray crystallographic study of BCHMX (C(4)H(6)N(8)O(8), M(r)=294.17), has been carried out at the temperature of 150K with the following results: a=8.5430(8), b=6.9480(6), c=8.7780(8)A, alpha=90.0(7) degrees , beta=102.452(11) degrees , gamma=90.0(9) degrees , V=508.777(8)A(3), Z=2, D(x)=1.920 g cm(-3), lambda(Mo Ka)=0.71073A, micro=0.169 cm(-1), F(000)=856, final R=0.0414 for 1254 independent observed reflections. In the BCHMX crystal there were found more short contacts in the molecular crystal of BCHMX data of Gilardi creating extensive supramolecular architecture. PMID:18926628

  6. (Z)-2,3-Di-chloro-1,4-bis-(4-chloro-phen-yl)but-2-ene-1,4-dione.

    PubMed

    Tittal, Ram K; Kumar, Satish; Ram, R N

    2014-08-01

    The title compound, C16H8Cl4O2, crystallizes with two independent mol-ecules in the asymmetric unit. Both mol-ecules have a Z conformation around the central double bond and they show significantly different C-C-C-O torsion angles between the aromatic ring and the carbonyl group [30.1 (7) and 3.9 (7)° in one molecule and 23.5 (7) and 9.3 (8)° in the other]. The crystal packing shows short halogen Cl⋯O [3.003 (5) and 3.246 (4) Å] and Cl⋯Cl [3.452 (2) Å] contacts and aromatic C-H⋯Cl and C-H⋯O inter-actions link the molecules, resulting in chains propogating along [100]. The crystal structure also features π-π stacking inter-actions between aromatic units of the two independent mol-ecules, with a centroid-centroid distance of 3.9264 (6) Å. PMID:25249911

  7. 77 FR 38799 - Draft Toxicological Review of 1,2,3-, 1,2,4-, and 1,3,5-Trimethylbenzene: In Support of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-29

    ...EPA is announcing a 60-day public comment period and a public listening session for the external review draft human health assessment titled ``Toxicological Review of 1,2,3-, 1,2,4-, and 1,3,5- Trimethylbenzene: In Support of Summary Information on the Integrated Risk Information System (IRIS)'' (EPA/635/R-11/012A). The draft assessment was prepared by the National Center for Environmental......

  8. Measuring phosphatidic acid phosphatase (EC 3.1.3.4) activity using two phosphomolybdate-based colorimetric methods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phosphatidate phosphatase (3-sn-phosphatidate phosphohydrolase, EC 3.1.3.4), which is also known as PAP, catalyzes the dephosphorylation of phosphatidate (PtdOH) to form diacylglycerol (DAG) and inorganic phosphate. In eukaryotes, PAP driven reaction is the committed step in the synthesis of triacyl...

  9. Synthesis of Novel Pyrido[4,3-e][1,2,4]triazino[3,2-c][1,2,4]thiadiazine 6,6-dioxide Derivatives with Potential Anticancer Activity.

    PubMed

    Sławiński, Jarosław; Grzonek, Aleksandra; Żołnowska, Beata; Kawiak, Anna

    2015-01-01

    A series of novel 3-/2,3-substituted pyrido[4,3-e][1,2,4]triazino[3,2-c][1,2,4]thiadiazine 6,6-dioxides 4-28 have been synthesized by the reaction of 3-amino-2-(4-thioxo-1,4-dihydropyridin-3-yl-sulfonyl)guanidine with either 2-oxoalkanoic acids and its esters, or phenylglyoxylic hydrates in glacial acetic acid. Some of them exhibited reasonable or moderate anticancer activity toward human cancer cell lines, HCT-116, MCF-7 and HeLa. The structure of this novel heterocyclic ring system was confirmed by ¹D-NMR and ²D-NMR spectroscopic data including COSY, ROESY and HMBC, elemental analyses and MS spectrometry. PMID:26729078

  10. [3a,4]-Dihydropyrazolo[1,5a]pyrimidines: Novel, Potent, and Selective Phosphatidylinositol-3-kinase β Inhibitors.

    PubMed

    Yu, Hongyi; Moore, Michael L; Erhard, Karl; Hardwicke, Mary Ann; Lin, Hong; Luengo, Juan I; McSurdy-Freed, Jeanelle; Plant, Ramona; Qu, Junya; Raha, Kaushik; Rominger, Cynthia M; Schaber, Michael D; Spengler, Michael D; Rivero, Ralph A

    2013-02-14

    A series of novel [3a,4]dihydropyrazolo[1,5a]pyrimidines were identified, which were highly potent and selective inhibitors of PI3Kβ. The template afforded the opportunity to develop novel SAR for both the hinge-binding (R3) and back-pocket (R4) substitutents. While cellular potency was relatively modest due to high protein binding, the series displayed low clearance in rat, mouse, and monkey. PMID:24900655

  11. [3a,4]-Dihydropyrazolo[1,5a]pyrimidines: Novel, Potent, and Selective Phosphatidylinositol-3-kinase β Inhibitors

    PubMed Central

    2013-01-01

    A series of novel [3a,4]dihydropyrazolo[1,5a]pyrimidines were identified, which were highly potent and selective inhibitors of PI3Kβ. The template afforded the opportunity to develop novel SAR for both the hinge-binding (R3) and back-pocket (R4) substitutents. While cellular potency was relatively modest due to high protein binding, the series displayed low clearance in rat, mouse, and monkey. PMID:24900655

  12. Inhibition of human pyridoxal kinase by 2-acetyl-4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)imidazole (THI).

    PubMed

    Elsinghorst, Paul W; di Salvo, Martino L; Parroni, Alessia; Contestabile, Roberto

    2015-04-01

    2-Acetyl-4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)imidazole (THI) is observed as a minor contaminant in caramel food colourings (E 150c). Feeding experiments with rodents have revealed a significant lymphopenic effect that has been linked to the presence of THI in these food colourings. Pyridoxal kinase inhibition by THI has been suggested, but not demonstrated, as a mode of action as it leads to lowered levels of pyridoxal-5'-phosphate, which are known to cause lymphopenia. Recently, THI was also shown to inhibit sphingosine-1-phosphate lyase causing comparable immunosuppressive effects and derivatives of THI are being developed for the treatment of rheumatoid arthritis in humans. Interestingly, sphingosine-1-phosphate lyase activity depends on pyridoxal-5'-phosphate, which in turn is provided by pyridoxal kinase. This report shows that THI does inhibit pyridoxal kinase with competitive and mixed-type non-competitive behaviour towards its two substrates, pyridoxal and ATP, respectively. The corresponding inhibition constants are in the low millimolar range. PMID:24899377

  13. 1-Phenyl-3-methyl-4-benzoyl-pyrazolone-5. A promising extractant for plutonium

    SciTech Connect

    Manchanda, V.K.; Mohapatra, P.K. )

    1994-05-01

    Pyrazolones and isoxazolones have been found to be promising extractants for metal ions, particularly from strong acidic media and in the presence of complexing anions. Extraction constants (log k[sub ex]) in toluene medium at 25[degree]C for PuX[sub 4] species, where X = 1-phenyl-3-methyl-4-acetyl-pyrazolone-5 (HPMAP), 1-phenyl-3-methyl-4-benzoyl-pyrazolone-5 (HPMBP), or 1-phenyl-3-methyl-4-(3:5-dinitro-benzoyl)pyrazolone-5 (HPMDP), are determined as 11.35 [+-] 0.04, 12.89 [+-] 0.03, and 12.73 [+-] 0.02, respectively. These values are comparable to the corresponding value for 3-phenyl-4-benzoyl-5-isoxazolone (HPBI) and several order of magnitude larger than that for 2-thenoyltrifluoroacetone (HTTA). A systematic study is carried out to investigate the extraction behavior of these [beta]-diketones toward plutonium present in the analytical waste solution obtained during the determination of uranium in a (U, Pu) fuel sample by the Davies Gray method. Whereas 0.3 M HPMBP extracts > 85% of the plutonium present in a single step, maximum extraction observed with other reagents is [much lt] 0.1% HTTA, 0.3% HPMAP, and 2.5% HPBI. The extraction of plutonium increases with different diluents in the order n-dodecane < n-hexane < CHCl[sub 3] < CCl[sub 4] < toluene. Extracted plutonium is quantitatively stripped with either 10 M HNO[sub 3] or 1:1 HCl + 0.1 M hydroquinone. 19 refs., 5 figs., 8 tabs.

  14. N-(3,4-Dimethyl-phen-yl)-4-hydr-oxy-2-methyl-2H-1,2-benzothia-zine-3-carboxamide 1,1-dioxide.

    PubMed

    Siddiqui, Waseeq Ahmad; Ali, Muhammad; Zia-Ur-Rehman, Muhammad; Sharif, Saima; Tizzard, Graham John

    2009-01-01

    1,2-Benzothia-zines similar to the title compound, C(18)H(18)N(2)O(4)S, are well known in the literature for their biological activities and are used as medicines in the treatment of inflammation and rheumatoid arthritis. The thia-zine ring adopts a distorted half-chair conformation. The enolic H atom is involved in an intra-molecular O-H⋯O hydrogen bond, forming a six-membered ring. In the crystal, mol-ecules arrange themselves into centrosymmetric dimers by means of pairs of weak inter-molecular N-H⋯O hydrogen bonds. PMID:21582605

  15. Pat1 protects centromere-specific histone H3 variant Cse4 from Psh1-mediated ubiquitination

    PubMed Central

    Mishra, Prashant K.; Guo, Jiasheng; Dittman, Lauren E.; Haase, Julian; Yeh, Elaine; Bloom, Kerry; Basrai, Munira A.

    2015-01-01

    Evolutionarily conserved histone H3 variant Cse4 and its homologues are essential components of specialized centromere (CEN)-specific nucleosomes and serve as an epigenetic mark for CEN identity and propagation. Cse4 is a critical determinant for the structure and function of the kinetochore and is required to ensure faithful chromosome segregation. The kinetochore protein Pat1 regulates the levels and spatial distribution of Cse4 at centromeres. Deletion of PAT1 results in altered structure of CEN chromatin and chromosome segregation errors. In this study, we show that Pat1 protects CEN-associated Cse4 from ubiquitination in order to maintain proper structure and function of the kinetochore in budding yeast. PAT1-deletion strains exhibit increased ubiquitination of Cse4 and faster turnover of Cse4 at kinetochores. Psh1, a Cse4-specific E3-ubiquitin ligase, interacts with Pat1 in vivo and contributes to the increased ubiquitination of Cse4 in pat1∆ strains. Consistent with a role of Psh1 in ubiquitination of Cse4, transient induction of PSH1 in a wild-type strain resulted in phenotypes similar to a pat1∆ strain, including a reduction in CEN-associated Cse4, increased Cse4 ubiquitination, defects in spatial distribution of Cse4 at kinetochores, and altered structure of CEN chromatin. Pat1 interacts with Scm3 and is required for its maintenance at kinetochores. In conclusion, our studies provide novel insights into mechanisms by which Pat1 affects the structure of CEN chromatin and protects Cse4 from Psh1-mediated ubiquitination for faithful chromosome segregation. PMID:25833709

  16. Fluorination of 1,2,3-, 1,2,4-, and 1,3,5-trihalobenzenes with potassium fluoride in dimethyl sulfone

    USGS Publications Warehouse

    Shiley, R.H.; Dickerson, D.R.; Finger, G.C.

    1972-01-01

    Three trifluorobenzenes were prepared by reaction of the corresponding trichlorobenzenes with potassium fluoride or pottassium fluoride-cesium fluoride mixtures in dimethyl sulfone. Molar yields were 12.8% for 1,2,3-, 8.3% for 1,2,4-, and 56.2% for 1,3,5-. Improved yields of the 1,2,3- (23.9%) and the 1,2,4- (34.0%) trifluorobenzenes were obtained from certain partially fluorinated intermediates. Several chlorofluorobenzene intermediates were obtained in goods yields by careful control of the reaction variables. The instability of the polyfluorobenzenes in the halogen-exchange reaction medium explains, in part, why only limited yields of the polyfluorobenzenes are obtained by using this method. ?? 1972.

  17. Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1).

    PubMed

    Bonifazi, Alessandro; Yano, Hideaki; Del Bello, Fabio; Farande, Aniket; Quaglia, Wilma; Petrelli, Riccardo; Matucci, Rosanna; Nesi, Marta; Vistoli, Giulio; Ferré, Sergi; Piergentili, Alessandro

    2014-11-13

    Novel bitopic hybrids, based on the M1/M4 muscarinic acetylcholine receptor (mAChR) orthosteric agonist xanomeline (1) and the putative M1 mAChR allosteric agonist 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1, 3) connected by an aliphatic linker of variable length, were prepared. The novel heterobivalent hybrids 4a-f along with the intermediate alcohols 5a-f were pharmacologically evaluated in radioligand binding assays and some of them for their functional efficacies in bioluminescence resonance energy transfer (BRET)-based assays to give an insight into the structure-activity relationships of bivalent and linker-attached compounds in mAChRs. The hybrid 4d exhibited high efficacy for β-arrestin2 engagement in M1 mAChR and alcohol 5c behaved much like 3 at M1 mAChR and showed full antagonism in both Gi activation and β-arrestin2 engagement at M4 mAChR. Moreover, docking simulations on the M1 mAChR model were performed to elucidate how the binding mode of the proposed compounds is influenced by the linker length. PMID:25275964

  18. 2,2-Dimethyl-5-(2,3,4-trimeth-oxy-benzyl-idene)-1,3-dioxane-4,6-dione.

    PubMed

    Zeng, Wu-Lan

    2011-08-01

    The title compound, C(16)H(18)O(7), was prepared by the reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione and 2,3,4-trimeth-oxy-benzaldehyde. The 1,3-dioxane ring is in a slightly distorted boat conformation. The crystal structure is stabilized by weak inter-molecular C-H⋯O hydrogen bonds. PMID:22090981

  19. Absorption of 2,4-Dichlorophenoxyacetic Acid and 3-(p-Chlorophenyl)-1, 1-dimethylurea (Monuron) by Barley Roots 1

    PubMed Central

    Donaldson, T. W.; Bayer, D. E.; Leonard, O. A.

    1973-01-01

    Absorption from culture solution of the herbicides 2, 4-dichlorophenoxyacetic acid (2, 4-D) and 3-(p-chlorophenyl)-1, 1-dimethylurea (Monuron) by excised barley (Hordeum vulgare L.) roots was studied to determine whether absorption was due to an active or a passive mechanism. Herbicide absorption was followed at low temperature, under anaerobic conditions, and in the presence of metabolic inhibitors and compounds of structure similar to that of the herbicide. Total absorption was divided into two phases, exchangeable and nonexchangeable herbicide, by washing the roots for 1 hour following absorption. Absorption of both exchangeable and non-exchangeable 2, 4-D appeared to depend on a supply of metabolic energy which suggests that an active mechanism may be involved. A possible conclusion is that 2, 4-D is absorbed by roots by an adsorption mechanism and that energy is required to maintain the integrity of the absorbing surfaces of the cell. In contrast, absorption of Monuron was independent of an energy supply. It is concluded that the bulk of the Monuron absorbed was taken up passively by diffusion. PMID:16658621

  20. Crystal structure of 2-amino-3-cyano-4-(4-meth-oxy-phen-yl)-4H-1-benzo-thieno[3,2-b]pyran.

    PubMed

    Bakhouch, Mohamed; El Yazidi, Mohamed; Kerbal, Abdelali; Saadi, Mohamed; El Ammari, Lahcen

    2015-12-01

    The three fused five- and six-membered rings in the title compound, C19H14N2O2S, are virtually coplanar, with the maximum deviation from the mean plane being 0.060 (1) Å. This benzothieno[3,2-b]pyran ring system is nearly perpendic-ular to the plane of the 4-meth-oxy-phenyl ring, forming a dihedral angle of 83.65 (5)°. In the crystal, mol-ecules are linked by pairs of N-H⋯N hydrogen bonds into inversion dimers. The dimeric units are further connected by an N-H⋯O hydrogen bond into a tape running along the b axis. The tapes are linked together by C-H⋯N and π-π inter-actions [centroid-centroid distance = 3.7743 (8) Å], forming a three-dimensional network. PMID:26870489

  1. Microbial Hydroxylation of 5-Anilino-1,2,3,4-Thiatriazole

    PubMed Central

    Theriault, Robert J.; Longfield, Thomas H.

    1973-01-01

    Two hundred eighty-five fungi, including 100 basidiomycetes and 35 yeasts, 75 actinomycetes, and 40 bacteria were screened for their ability to convert 5-anilino-1,2,3,4-thiatriazole (AT) to 5-(p-hydroxyanilino)-1,2,3,4-thiatriazole (p-HT). Eleven cultures were found that formed p-HT, which was isolated and whose structure was determined. Aspergillus tamarii NRRL 3280 formed 8.6 g of p-HT/liter from 10 g of AT/liter (78.9% conversion) in shaken flasks and 4.57 g of p-HT/liter from 6 g of AT/liter (69.8% conversion) in 30-liter fermentors. Washed cells of A. tamarii NRRL 3280 also carried out this conversion. 5-(o-hydroxyanilino)-1,2,3,4-thiatriazole (o-HT) was identified as a second product formed by Aspergillus terreus NRRL 1960. PMID:4699219

  2. Topology of the maize mixed linkage (1->3),(1->4)-beta-d-glucan synthase at the Golgi membrane.

    PubMed

    Urbanowicz, Breeanna R; Rayon, Catherine; Carpita, Nicholas C

    2004-02-01

    Mixed-linkage (1-->3),(1-->4)-beta-d-glucan is a plant cell wall polysaccharide composed of cellotriosyl and cellotetraosyl units, with decreasingly smaller amounts of cellopentosyl, cellohexosyl, and higher cellodextrin units, each connected by single (1-->3)-beta-linkages. (1-->3),(1-->4)-beta-Glucan is synthesized in vitro with isolated maize (Zea mays) Golgi membranes and UDP-[(14)C]d-glucose. The (1-->3),(1-->4)-beta-glucan synthase is sensitive to proteinase K digestion, indicating that part of the catalytic domain is exposed to the cytoplasmic face of the Golgi membrane. The detergent [3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid] (CHAPS) also lowers (1-->3),(1-->4)-beta-glucan synthase activity. In each instance, the treatments selectively inhibit formation of the cellotriosyl units, whereas synthesis of the cellotetraosyl units is essentially unaffected. Synthesis of the cellotriosyl units is recovered when a CHAPS-soluble factor is permitted to associate with Golgi membranes at synthesis-enhancing CHAPS concentrations but lost if the CHAPS-soluble fraction is replaced by fresh CHAPS buffer. In contrast to other known Golgi-associated synthases, (1-->3),(1-->4)-beta-glucan synthase behaves as a topologic equivalent of cellulose synthase, where the substrate UDP-glucose is consumed at the cytosolic side of the Golgi membrane, and the glucan product is extruded through the membrane into the lumen. We propose that a cellulose synthase-like core catalytic domain of the (1-->3),(1-->4)-beta-glucan synthase synthesizes cellotetraosyl units and higher even-numbered oligomeric units and that a separate glycosyl transferase, sensitive to proteinase digestion and detergent extraction, associates with it to add the glucosyl residues that complete the cellotriosyl and higher odd-numbered units, and this association is necessary to drive polymer elongation. PMID:14730082

  3. 1,2,3-thiadiazole thioacetanilides. Part 2: Synthesis and biological evaluation of a new series of 2-{[4-(3,4-dichlorophenyl)-1,2,3-thiadiazol-5-yl]sulfanyl}acetanilides as HIV-1 inhibitors.

    PubMed

    Zhan, Peng; Liu, Xin-Yong; Li, Zhen-Yu; Fang, Zeng-Jun; Pannecouque, Christophe; De Clercq, Erik

    2010-07-01

    As part of our studies to discover new HIV-1 reverse transcriptase inhibitors, a series of 3,4-dichlorophenyl substituted 1,2,3-thiadiazole thioacetanilide (TTA=[(1,2,3-thiadiazole-5-yl)sulfanyl]acetanilide) derivatives were synthesized, and in vitro anti-HIV activity was evaluated. The results revealed that nearly half of the compounds show moderate-to-good inhibitory potency against HIV-1. In particular, compound 7f is highly potent, with an EC(50) value of 0.95+/-0.33 microM. The preliminary structure-activity relationship among the newly synthesized congeners is discussed. PMID:20658659

  4. Synthesis and Pharmacological Evaluation of Novel 1-(1,4-Alkylaryldisubstituted-4,5-dihydro-1H-imidazo)-3-substituted Urea Derivatives.

    PubMed

    Szacoń, Elżbieta; Rządkowska, Marzena; Kaczor, Agnieszka A; Kędzierska, Ewa; Orzelska-Górka, Jolanta; Fidecka, Sylwia; Matosiuk, Dariusz

    2016-01-01

    Novel 1-(1,4-alkylaryldisubstituted-4,5-dihydro-1H-imidazo)-3-substituted urea derivatives have been synthesized and evaluated for their central nervous system activity. Compounds 3a-m were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a-c and appropriate isocyanates 2 in dichloromethane. The compounds were subjected to in silico ADMET studies in order to select best candidates for in vivo experiments. The effects of the compounds on the spontaneous locomotor activity and amphetamine-evoked hyperactivity were estimated. Analgesic activity, without or in the presence of naloxone, was assessed in the writhing test. The tendency to change the HTR, evoked by l-5-HTP and the involvement in alteration in body temperature in mice was studied. Additionally, to check possible occurrence of drug-induced changes in the muscle relaxant activity of mice, which may have contributed to their behaviour in other tests, the rota-rod and chimney tests were performed. The new urea derivatives exerted significant activities in the performed pharmacological tests, although the presented results show a preliminary estimation, and thus, need to be extended for identification and understanding the complete pharmacological profile of the examined compounds. PMID:27144554

  5. Synthesis and crystal structure of a copper complex with (E)-2-(4-(1H-1,2,4-triazol-1-yl)benzylidene)-3, 4-dihydronaphthalen-1(2H)-one ligand

    SciTech Connect

    Sun, Shu-Wen; Zhang, Xiao; Wang, Gao-Feng

    2015-12-15

    The title compound, C{sub 35}H{sub 23}CuF{sub 6}N{sub 3}O{sub 5}S{sub 2} (1), was synthesized by the reaction of Cu(tta){sub 2} and L{sup 1}, (L{sup 1} = (E)-2-(4-(1H-1,2,4-triazol-1-yl)benzylidene)-3, 4-dihydronaphthalen-1(2H)-one) in the dichloromethane solution. It crystallizes in the monoclinic, space group P2{sub 1}/c with a = 33.8388(5), b = 9.3874(2), c = 21.8194(4) Å, β = 95.522(2), V = 6898.9(2) Å{sup 3}, Z = 8, D{sub x} = 1.554 Mg/m{sup 3}, F(000) = 3272, µ = 0.834 mm{sup –1}, R{sub 1} = 0.0639, wR{sub 2} = 0.1637. The copper(II) ion of 1 is in a distorted square-pyramidal environment with four O atoms of the two tta ligands and one N atom of triazole ligand L{sup 1}. Single-crystal X-ray diffraction data revealed that the hydrogen bonds, weak C–H···π and π···π interactions in the crystals link the coordination units to form 3D supramolecular structures.

  6. 3-nitro-1,2,4-triazol-5-one: A less sensitive explosive

    DOEpatents

    Lee, Kien-Yin; Coburn, M.D.

    1987-01-30

    A less sensitive explosive, 3-nitro-1,2,4-triazol-5-one. The compound 3-nitro--1,2,4-triazol-5-one (NTO) has a crystal density of 1.93 g/cm/sup 3/ and calculated detonation velocity and pressure equivalent to those of RDX. It can be prepared in high yield from inexpensive starting materials in a safe synthesis. Results from initial small-scale sensitivity tests indicate that NTO is less sensitive than RDX and HMX in all respects. A 4.13 cm diameter, unconfined plate-dent test at 92% of crystal density gave the detonation pressure predicted for NTO by the BKW calculation. 3 tabs.

  7. Preparation of 1,3,5-triamino-2,4,6-trinitrobenzene of submicron particle size

    DOEpatents

    Rigdon, Lester P.; Moody, Gordon L.; McGuire, Raymond R.

    2001-01-01

    A method is disclosed for the preparation of very small particle size, relatively pure 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). Particles of TATB prepared according to the disclosed method are of submicron size and have a surface area in the range from about 3.8 to 27 square meters per gram.

  8. Preparation of 1,3,5-triamo-2,4,6-trinitrobenzene of submicron particle size

    DOEpatents

    Rigdon, Lester P.; Moody, Gordon L.; McGuire, Raymond R.

    2001-05-01

    A method is disclosed for the preparation of very small particle size, relatively pure 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). Particles of TATB prepared according to the disclosed method are of submicron size and have a surface area in the range from about 3.8 to 27 square meters per gram.

  9. STS-105 Mission Highlights Resource Tape: Flight Days 1-3. Part 1 of 4

    NASA Technical Reports Server (NTRS)

    2002-01-01

    An overview of the STS-105 mission is given through footage of each flight day. Scenes from flight days one through three show activities such as astronaut prelaunch procedures (breakfast, suit-up, and boarding Discovery), the launch from multiple vantage points, and various on-orbit activities. Expedition 3 (E3) Commander Frank Culbertson, Jr. and Flight Engineer Mikhail Turin perform the H-Reflex Experiment, an experiment to test the effects of microgravity on the human spinal cord. As Discovery approaches the International Space Station (ISS), the Expedition 2 (E2) crew, Commander Yuriy Usachev and Flight Engineers James Voss and Susan Helms, are seen working in the Destiny Laboratory Module aboard ISS. Discovery docks to the space station and the three crews (STS-105, E2, and E3) greet each other after the hatches between the orbiter and ISS are opened. As Discovery passes over the United States, Utah, Wyoming, South Dakota, and Minnesota are seen through patchy clouds. Footage from flight days 4-13 can be found on 'STS-105 Mission Highlights Resource Tape: Flight Days 4-6' (internal ID 2002046549), 'STS-105 Mission Highlights Resource Tape: Flight Days 7-9' (internal ID 2002046552), and 'STS-105 Mission Highlights Resource Tape: Flight Days 10-13' (internal ID 2002046551).

  10. 1,3,4-Oxadiazole-containing histone deacetylase inhibitors: anticancer activities in cancer cells.

    PubMed

    Valente, Sergio; Trisciuoglio, Daniela; De Luca, Teresa; Nebbioso, Angela; Labella, Donatella; Lenoci, Alessia; Bigogno, Chiara; Dondio, Giulio; Miceli, Marco; Brosch, Gerald; Del Bufalo, Donatella; Altucci, Lucia; Mai, Antonello

    2014-07-24

    We describe 1,3,4-oxadiazole-containing hydroxamates (2) and 2-aminoanilides (3) as histone deacetylase inhibitors. Among them, 2t, 2x, and 3i were the most potent and selective against HDAC1. In U937 leukemia cells, 2t was more potent than SAHA in inducing apoptosis, and 3i displayed cell differentiation with a potency similar to MS-275. In several acute myeloid leukemia (AML) cell lines, as well as in U937 cells in combination with doxorubicin, 3i showed higher antiproliferative effects than SAHA. PMID:24972008

  11. Synthesis, structural, conformational and pharmacological study of some carbamates derived from 3-methyl-2,4-diphenyl-3- azabicyclo[3.3.1]nonan-9α-ol

    NASA Astrophysics Data System (ADS)

    Iriepa, I.; Gil-Alberdi, B.; Gálvez, E.; Bellanato, J.; Carmona, P.

    1997-04-01

    A series of benzimidazole and benzothiazole carbamates derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9α-ol has been synthesized and studied by IR, Raman, 1H and 13C NMR spectroscopy. The compounds studied display in CDCl 3 a preferred flattened chair-chair conformation. IR (at room and variable temperature) and 1H and 13C NMR data show the presence of an intramolecular NH…OC hydrogen bond in the benzimidazole carbamates. Pharmacological assays on mice were performed to evaluate analgesic activity as well as drug-induced behavioral alterations.

  12. Synthesis, structural, conformational and pharmacological study of some carbamates derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9 β-ol

    NASA Astrophysics Data System (ADS)

    Iriepa, I.; Gil-Alberdi, B.; Gálvez, E.; Villasante, F. J.; Bellanato, J.; Carmona, P.

    1999-05-01

    A series of benzimidazole and benzothiazole carbamates derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9 β-ol were synthesized and studied by IR, Raman, 1H and 13C NMR spectroscopy. The compounds studied displayed in CDCl 3 solution a preferred flattened chair-chair conformation. IR and 1H and 13C NMR data showed the presence of an intramolecular hydrogen bond in the benzimidazole carbamates. Pharmacological assays on mice were drawn to evaluate analgesic activity as well as drug-induced behavioral alterations.

  13. Synthesis and in vitro antibacterial activity of 7-(3-alkoxyimino-4-amino-4-methylpiperidin-1-yl) fluoroquinolone derivatives.

    PubMed

    Wang, Ju-Xian; Zhang, Yi-Bin; Liu, Ming-Liang; Wang, Bo; Chai, Yun; Li, Su-Jie; Guo, Hui-Yuan

    2011-06-01

    A series of novel 7-(3-alkoxyimino-4-amino-4-methylpiperidin-1-yl)fluoroquinolone derivatives were designed, synthesized and evaluated for their in vitro antibacterial activity and cytotoxicity. All of the target compounds have potent antibacterial activity against the tested Gram-positive and Gram-negative strains, and exhibit good potency in inhibiting the growth of Staphylococcus aureus including MRSA, Staphylococcus epidermidis including MRSE and Streptococcus pneumoniae (MICs: 0.125-4 μg/mL). Compound 22, with the best activity against Gram-positive strains, is 4-16 fold more potent than gemifloxacin, gatifloxacin and levofloxacin against Enterococcus faecalis, and 16- and 4-fold more potent than levofloxacin against S. epidermidis 09-6 and S. pneumoniae 08-4, respectively. PMID:21481984

  14. Crystal structure and spectroscopic study on photochromism of 1,3-diphenyl-4-(4‧-fluoro)benzal-5-pyrazolone N(4)-phenyl semicarba-zone

    NASA Astrophysics Data System (ADS)

    Chai, Hui; Liu, Guangfei; Liu, Lang; Jia, Dianzeng; Guo, Zaiping; Lang, Jianping

    2005-10-01

    A novel compound 1,3-diphenyl-4-(4'-fluoro)benzal-5-pyrazolone N(4)-phenyl semicarbazone (DP4FBP-PSC) has been synthesized. X-ray single crystal structure analysis shows that the compound has interlaced structure linked by intermolecular hydrogen bonds. The results of fluorescence emission spectroscopy, UV-Vis reflection spectroscopy and the reaction rate constant indicate that DP4FBP-PSC is photochromic material. Its photochromic mechanism was investigated by structure analysis.

  15. Synthesis and biological activity of hydrazide hydrazones and their corresponding 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Various new 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles (11-20) were prepared by the reaction of aryl substituted hydrazones of 4-fluorobenzoic acid hydrazide (1-10) with acetic anhydride. The structures of the newly synthesized compounds 11-20, were confirmed by UV, IR and 1H NMR spec...

  16. 4-(3,5-Dimethyl-1H-pyrazol-1-yl)benzene­sulfonamide

    PubMed Central

    Asiri, Abdullah M.; Faidallah, Hassan M.; Al-Youbi, Abdulrahman O.; Ng, Seik Weng

    2011-01-01

    The two aromatic rings of the title compound, C11H13N3O2S, are inclined at an angle of 47.81 (4)°. The N atom of the amino unit is pyramidally coordinated; one H atom inter­acts with the sulfamyl O atom of an adjacent mol­ecule, forming a centrosymmetric hydrogen-bonded dimer. The dimers are linked by N—H⋯N hydrogen bonds, generating a three-dimensional network. PMID:22064356

  17. Synthesis and crystal structure of a copper complex with ( E)-2-(4-(1 H-1,2,4-triazol-1-yl)benzylidene)-3,4-dihydronaphthalen-1(2 H)-one ligand

    NASA Astrophysics Data System (ADS)

    Sun, Shu-Wen; Zhang, Xiao; Wang, Gao-Feng

    2015-12-01

    The title compound, C35H23CuF6N3O5S2 ( 1), was synthesized by the reaction of Cu( tta)2 and L 1, ( L 1 = ( E)-2-(4-(1 H-1,2,4-triazol-1-yl)benzylidene)-3,4-dihydronaphthalen-1(2 H)-one) in the dichloromethane solution. It crystallizes in the monoclinic, space group P21/ c with a = 33.8388(5), b = 9.3874(2), c = 21.8194(4) Å, β = 95.522(2), V = 6898.9(2) Å3, Z = 8, D x = 1.554 Mg/m3, F(000) = 3272, µ = 0.834 mm-1, R 1 = 0.0639, wR 2 = 0.1637. The copper(II) ion of 1 is in a distorted square-pyramidal environment with four O atoms of the two tta ligands and one N atom of triazole ligand L 1. Single-crystal X-ray diffraction data revealed that the hydrogen bonds, weak C-H···π and π···π interactions in the crystals link the coordination units to form 3D supramolecular structures.

  18. Synthesis of 2H-1,3-benzoxazin-4(3H)-one derivatives containing indole moiety: their in vitro evaluation against PDE4B.

    PubMed

    Rao, Raja Mohan; Luther, Bethala Jawahar; Rani, Chekuri Sharmila; Suresh, Namburi; Kapavarapu, Ravikumar; Parsa, Kishore V L; Rao, Mandava V Basaveswara; Pal, Manojit

    2014-02-15

    A number of 2H-1,3-benzoxazin-4(3H)-one derivatives containing indole or benzofuran moieties were synthesized by using Pd/C-Cu mediated coupling-cyclization strategy as a key step. The o-iodoanilides or o-iodophenol were coupled with 3-{2-(prop-2-ynyloxy)ethyl}-2H-benzo[e][1,3]oxazin-4(3H)-one using 10%Pd/C-CuI-PPh3 as a catalyst system and Et3N as a base to give the target compounds. All the synthesized compounds were tested for their PDE4B inhibitory potential in vitro using a cell based cAMP reporter assay. Some of them showed fold increase of the cAMP level when tested at 30 μM. A representative compound showed encouraging PDE4B inhibitory properties that were supported by its docking results. PMID:24440301

  19. 4-Hydroxyderricin, as a PPARγ Agonist, Promotes Adipogenesis, Adiponectin Secretion, and Glucose Uptake in 3T3-L1 Cells.

    PubMed

    Li, Yongjia; Goto, Tsuyoshi; Yamakuni, Kanae; Takahashi, Haruya; Takahashi, Nobuyuki; Jheng, Huei-Fen; Nomura, Wataru; Taniguchi, Masahiko; Baba, Kimiye; Murakami, Shigeru; Kawada, Teruo

    2016-07-01

    Adipocyte differentiation plays a pivotal role in maintaining the production of small-size adipocytes with insulin sensitivity, and impaired adipogenesis is implicated in insulin resistance. 4-Hydroxyderricin (4-HD), a phytochemical component of Angelica keiskei, possesses diverse biological properties such as anti-inflammatory, antidiabetic, and antitumor. In the present study, we investigated the effects of 4-HD on adipocyte differentiation. 4-HD promoted lipid accumulation in 3T3-L1 cells, upregulated both peroxisome proliferator-activated receptor (PPAR)-γ mRNA and protein expression, and acted as a ligand for PPARγ in the luciferase assay. Moreover, 4-HD increased the mRNA and protein expression levels of adiponectin. Additionally, it promoted insulin-dependent glucose uptake into 3T3-L1 adipocytes and increased Akt phosphorylation and glucose transporter (GLUT) 4 mRNA expression. In summary, these findings suggest that 4-HD, which promoted adipogenesis and insulin sensitivity in 3T3-L1 cells, might be a phytochemical with potent insulin-sensitizing effects. PMID:27098252

  20. New potent inhibitors of tyrosinase: novel clues to binding of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxadiazole-2(3H)-thiones, 4-amino-1,2,4-triazole-5(4H)-thiones, and substituted hydrazides to the dicopper active site.

    PubMed

    Ghani, Usman; Ullah, Nisar

    2010-06-01

    A series of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxadiazole-2(3H)-thiones, 4-amino-1,2,4-triazole-5(4H)-thiones, and substituted hydrazides were tailored and synthesized as new potent inhibitors of tyrosinase. The rationale for inhibitor design was based on the active site structural evidence from the crystal structures of bacterial tyrosinase and potato catechol oxidase enzymes. Kinetic and active site binding studies suggested mono-dentate binding of thiadiazole, oxadiazole, and triazole rings to the active site dicopper center of tyrosinase including hydrophobicity contributing to the potent inhibition. Kinetic plots showed mixed-type of inhibition by all 25 compounds. Substitutions at C3 of the triazole ring and C5 of the thiadiazole/oxadiazole rings were found to be playing a major role in the high binding affinity to tyrosinase. The current work may help develop new potent tyrosinase inhibitors against hyperpigmentation including potential insecticides. PMID:20452224

  1. Stereochemical course and structure of the products of the enzymic action of endo-1,3-1,4-beta-D-glucan 4-glucanohydrolase from Bacillus licheniformis.

    PubMed Central

    Malet, C; Jiménez-Barbero, J; Bernabé, M; Brosa, C; Planas, A

    1993-01-01

    The stereochemical course of the reaction catalysed by endo-1,3-1,4-beta-D-glucan 4-glucanohydrolase (EC 3.2.1.73) has been determined by 1H n.m.r. The enzyme-catalysed hydrolysis of barley beta-glucan proceeds with overall retention of the anomeric configuration, indicating that the enzyme operates through a double-displacement mechanism. The structures of the final oligosaccharide products, 3-beta-O-cellobiosyl D-glucopyranoside and 3-beta-O-cellotriosyl D-glucopyranoside, have been completely assigned by 1H- and 13C-n.m.r. spectroscopy. PMID:8280073

  2. Binding properties of nine 4-diphenyl-acetoxy-N-methyl-piperidine (4-DAMP) analogues to M1, M2, M3 and putative M4 muscarinic receptor subtypes.

    PubMed Central

    Waelbroeck, M.; Camus, J.; Tastenoy, M.; Christophe, J.

    1992-01-01

    1. We compared the binding properties of 4-diphenyl-acetoxy-N-methyl-piperidine methiodide (4-DAMP) and nine analogues of this compound on muscarinic receptors of human neuroblastoma NB-OK1 cells (M1 subtype), rat heart (M2 subtype), rat pancreas (M3 subtype) and to the putative M4 subtype in striatum. 2. The requirements for high affinity binding were somewhat different for the four receptor subtypes. In general, the requirements of M3 receptors were more stringent than for M1, M2 or putative M4 receptors. 3. The abilities of the compounds to discriminate muscarinic receptor subtypes were not correlated with their affinities at any subtype. 4. The temperature-dependence of binding of 4-DAMP analogues to M2 receptors varied with the drug structure. In particular, the increased affinity of the alpha-methyl derivative of 4-DAMP could be ascribed to van der Waals interactions. 5. The affinities of most 4-DAMP analogues for M2 and M3 receptors were similar to their pharmacological potencies on atrial and ileum preparations, respectively. 6. At concentrations above 1 microM, all 4-DAMP analogues as well as atropine, reduced the [3H]-N-methyl scopolamine ([3H]-NMS) dissociation rate from cardiac muscarinic receptors, with no obvious structure-activity relationship. PMID:1596694

  3. Synthesis, molecular structure and characterization of allylic derivatives of 6-amino-3-methyl-1,2,4-triazolo[3,4-f][1,2,4]-triazin-8(7H)-one.

    PubMed

    Hwang, Long-Chih; Jane, Shin-Yi; Lai, Hsing-Yi; Tu, Chun-Hsien; Lee, Gene-Hsiang

    2006-01-01

    1-Allyl- (2) and 7-allyl-6-amino-3-methyl-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-one (3) were obtained via the 18-crown-6-ether catalyzed room temperature reaction of 6-amino-3-methyl-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-one (1) with potassium carbonate and allyl bromide in dry acetone. The structures of these two derivatives were verified by 2D-NMR measurements, including gHSQC and gHMBC measurements. The minor compound 2 may possess aromatic character. A single crystal X-ray diffraction experiment indicated that the major compound 3 crystallizes from dimethyl sulfoxide in the monoclinic space group P2(1)/n and its molecular structure includes an attached dimethylsulfoxide molecule, resulting in the molecular formula C(10)H(16)N(6)O(2)S. Molecular structures of 3 are linked by extensive intermolecular N-H...N hydrogen bonding [graph set C(1)(1)(7)]. 1 Each molecule is attached to the dimethyl sulfoxide oxygen via N-H...O intermolecular hydrogen bonding. The structure is further stabilized by pi-pi stacking interactions. PMID:17962777

  4. 4. PART 1 OF 3 PART PANORAMA WITH NOS. CA265J5 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. PART 1 OF 3 PART PANORAMA WITH NOS. CA-265-J-5 AND CA-265-J-6 OF FIGUEROA STREET AND LOS ANGELES RIVER VIADUCTS. NOTE TUNNEL NO.1 NORTH PORTAL AT LEFT REAR. LOOKING 268°W. - Arroyo Seco Parkway, Figueroa Street Viaduct, Spanning Los Angeles River, Los Angeles, Los Angeles County, CA

  5. 42 CFR 84.100 - Man tests 1, 2, 3, and 4; requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Man tests 1, 2, 3, and 4; requirements. 84.100 Section 84.100 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self-Contained Breathing Apparatus § 84.100 Man tests...

  6. 42 CFR 84.100 - Man tests 1, 2, 3, and 4; requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Man tests 1, 2, 3, and 4; requirements. 84.100 Section 84.100 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self-Contained Breathing Apparatus § 84.100 Man tests...

  7. 42 CFR 84.100 - Man tests 1, 2, 3, and 4; requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Man tests 1, 2, 3, and 4; requirements. 84.100 Section 84.100 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self-Contained Breathing Apparatus § 84.100 Man tests...

  8. 42 CFR 84.100 - Man tests 1, 2, 3, and 4; requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Man tests 1, 2, 3, and 4; requirements. 84.100 Section 84.100 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self-Contained Breathing Apparatus § 84.100 Man tests...

  9. 42 CFR 84.100 - Man tests 1, 2, 3, and 4; requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Man tests 1, 2, 3, and 4; requirements. 84.100 Section 84.100 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self-Contained Breathing Apparatus § 84.100 Man tests...

  10. In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)

    DOE PAGESBeta

    Choi, Taylor A.; Furimsky, Anna M.; Swezey, Robert; Bunin, Deborah I.; Byrge, Patricia; Iyer, Lalitha V.; Chang, Polly Y.; Abergel, Rebecca J.

    2015-02-27

    We report that the hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 minutes, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) ismore » unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of co-administered drugs metabolized by these enzymes. Plasma protein binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bi-directional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies.« less

  11. In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)

    SciTech Connect

    Choi, Taylor A.; Furimsky, Anna M.; Swezey, Robert; Bunin, Deborah I.; Byrge, Patricia; Iyer, Lalitha V.; Chang, Polly Y.; Abergel, Rebecca J.

    2015-02-27

    We report that the hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 minutes, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) is unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of co-administered drugs metabolized by these enzymes. Plasma protein binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bi-directional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies.

  12. In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)

    PubMed Central

    Choi, Taylor A.; Furimsky, Anna M.; Swezey, Robert; Bunin, Deborah I.; Byrge, Patricia; Iyer, Lalitha V.; Chang, Polly Y.; Abergel, Rebecca J.

    2015-01-01

    The hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 minutes, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) is unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of co-administered drugs metabolized by these enzymes. Plasma protein binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bi-directional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies. PMID:25727482

  13. Synthesis and spectral characterization of bis(4-amino-5-mercapto-1,2,4-triazol-3-yl)propane

    NASA Astrophysics Data System (ADS)

    Subashchandrabose, S.; Thanikachalam, V.; Manikandan, G.; Saleem, H.; Erdogdu, Y.

    2016-03-01

    Bis(4-amino-5-mercapto-1,2,4-triazol-3-yl)propane (BAMTP) was synthesized and characterized by FT-IR and FT-Raman spectra. Gas phase structure of BAMTP was examined under density functional theory B3LYP/6-311 ++G(d, p) level of basis set, wherein the molecule was subjected to conformational analysis. Thus the identified stable structure utilized for the calculations such as geometry optimization, vibrational behavior, hyperpolarizability analysis, natural bond orbital analysis, band gap, chemical hard/softness and stability. Geometry of BAMTP has been discussed elaborately with related crystal data. The results found from experimental and theoretical methods were reported herewith.

  14. [Effects of N, N'-Di-(m-methylphenyi)-3, 6-dimethyl-1, 4-dihydro-1, 2, 4, 5-tetrazine-1, 4-dicarboamide on proliferation, apoptosis and differentiation of NB4 leukemia cells in vitro].

    PubMed

    Zhou, Yong-Lie; Lü, Ya-Ping; Hu, Wei-Xiao; Qiu, Lian-Nü; Wang, Wen-Song; Wu, Jian-Guo; Liu, Jian-Dong

    2006-10-01

    The purpose of this study was to explore the effect of N, N'-di-(m-methylphenyi)-3, 6-dimethyl-1, 4-dihydro-1, 2, 4, 5-tetrazine-1, 4-dicarboamide (ZGDHu-1) on proliferation, differentiation and apoptosis in NB4 human leukemia cell line and its possible mechanism. Different concentrations of ZGDHu-1 and the different time of cultivation were used to treat NB4 cells. The proliferation inhibition of NB4 cells was analysed by cell counting, alive cell count, MTT assay. Cell apoptosis was determined by cell morphology, DNA agarose gel electrophoresis, DNA content, Annexin-V/PI and Hoechst 33258 labeling method. The analysis of cell morphological change, expression of CD11b, CD13 and NBT reduction were performed to evaluate the differentiation of NB4 cells. The expressions of bcl-2, bax and phosphorylated p38MAPK or STAT3 were detected by flow cytometry. While the expression of hTERT mRNA in transcriptional level was measured by fluorescence quantitative RT-PCR. The results showed that ZGDHu-1 could inhibit NB4 cell proliferation viability within a certain range of treating time and does, IC(50) values at 48 and 72 hours were 450 ng/ml and 200 ng/ml respectively. A majority of NB4 cells were arrested in G(2/M) phase and a progressive decline of cells was seen in G(0/1). The NB4 cells apoptosis was confirmed by cell typical cell morphology, DNA fragments and sub-G(1) phase peak as well as Hoechst33258 and Annexin-V/PI labeling method with a time-dose-related manner. The morphology of NB4 cells cultured in the presence of 2 - 100 ng/ml ZGDHu-1 for three days was more mature with higher NBT positivity and expressions of CD11b and CD13 than those in control. The expression of phosphor-p38MAPK and bax was increased while phosphor-STAT3 and bcl-2 were unchanged by the treatment of ZGDHu-1. ZGDHu-1 could decrease the expression of hTERT-mRNA in a dose-dependent manner. It is concluded that ZGDHu-1 can inhibit proliferation, induce differentiation and apoptosis of NB4 cells

  15. 5-(4-Chloro­phen­yl)-1-methyl-3-phenyl-3,6,8,9-tetra­hydro­pyrazolo­[3,4-b]thio­pyrano[4,3-d]pyridine

    PubMed Central

    Jia, Runhong; Peng, Juhua

    2011-01-01

    The title compound, C22H18ClN3S, was synthesized by the reaction of 4-chloro­benzaldehyde, tetra­hydro­thio­pyran-4-one and 3-methyl-1-phenyl-1H-pyrazol-5-amine in acetic acid without a catalyst. The pyridine and pyrazole rings are almost coplanar, the dihedral angle between their mean planes being 2.50 (1)°. The thio­pyran ring exhibits an envelope conformation. The crystal packing is stabilized by inter­molecular C—H⋯Cl hydrogen bonds and by C—H⋯π and π–π inter­actions [centroid–centroid distances of 3.825 (2) Å between pyridine rings and 3.557 (2) Å between pyrazole and pyridine rings. PMID:22059005

  16. Synthesis and properties of amides of 1-benzyl-3-methyl- and 1-butyl-3-phenyl-7-methyl-4-oxo-2-thioxo (2,4-dioxo)-1,2,3,4-tetrahydropyrido-[2,3-d]pyrimidine-6-carboxy lic acids.

    PubMed

    Sladowska, H; Zawisza, T

    1986-12-01

    Amides of 1-benzyl-3,7-dimethyl-4-oxo-2-thioxo-1,2,3,4- tetrahydropyrido[2,3]pyrimidine-6-carboxylic acid were obtained by the condensation of ammonia, primary and secondary cyclic amines with the corresponding acid chloride. As by - products amides of 1-benzyl-3,7-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyr imidine-6- carboxylic acid were isolated as a result of desulfuration. The same reaction performed with chloride of 1-butyl-7-methyl-3-phenyl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyri do[2,3- d]pyrimidine-6-carboxylic acid gave mainly the corresponding 2,4-dioxo-amides. PMID:3556569

  17. X-ray diffraction and spectral studies of 1-phenyl-3-methyl-4-(2',4'-dimethylphenylazo)-pyrazolone-5

    SciTech Connect

    Kuz'mina, L.G.; Grigor'eva, L.P.; Struchkov, Yu.T.; Ezhkova, Z.I.; Zaitsev, B.E.; Zaitseva, V.A.; Pron'kin, P.P.

    1985-12-01

    The molecular and crystal structures of 1-phenyl-3-methyl-4-(2',4'-dimethyl-phenylazo)pyrazolone-5 were determined. In the crystal the molecule exists as the hydrazone tautomer. The pyrazole ring is planar, and the substituents are practically coplanar with it. The molecule contains an intramolecular NH...O hydrogen bond that closes a practically planar six-membered ring (N...O, 2.77 (I), H...O 2.14 A, angle at H(N/sub (4)/) hydrogen 131/sup 0/). The x-ray diffraction data agree with the spectral data and with the CNO calculation.

  18. In vitro BALB/3T3 cell transformation assay of nonoxynol-9 and 1,4-dioxane

    SciTech Connect

    Sheu, C.W.; Moreland, F.M.; Lee, J.K.; Dunkel, V.C.

    1988-01-01

    The spermicidal surfactant nonoxynol-9 (Igepal CO-630, GAF Corp.) and a potential impurity, 1,4-dioxane, were tested in the in vitro cell transformation assay using BALB/3T3 cells. Two treatment periods, 48 hr and 13 days, were used. Nonoxynol-9, tested at levels up to 10 /sup +/g/ml, did not induce transformation, whereas dioxane was very active in the induction type II foci in the cultured BALB/3T3 cells.

  19. 1-(3,5-Di­fluoro­phen­yl)-4,4,4-tri­fluoro­butane-1,3-dione

    PubMed Central

    Manoj Kumar, K.E.; Palakshamurthy, B. S.; Suchetan, P. A.; Madan Kumar, S.; Lokanath, N.K.; Sreenivasa, S.

    2013-01-01

    In the title compound, C10H5F5O2, the C=O bonds are syn to one another. In the crystal, mol­ecules are linked into C(9) chains parallel to [101] through weak C—H⋯O inter­actions, with the O atom adjacent to the –CF3 group acting as the acceptor. PMID:24454131

  20. 2-[3-(4-Bromo­phenyl)-5-(4-fluoro­phenyl)-4,5-di­hydro-1H-pyrazol-1-yl]-4-phenyl-1,3-thia­zole

    PubMed Central

    Abdel-Wahab, Bakr F.; Mohamed, Hanan A.; Ng, Seik Weng; Tiekink, Edward R. T.

    2013-01-01

    In the title compound, C24H17BrFN3S, the pyrazole ring is almost planar (r.m.s. deviation = 0.043 Å), with all but the perpendicular fluoro­benzene ring substituents [dihedral angle = 77.9 (3)°] being very approximately coplanar [dihedral angle with the 2-thienyl ring = 19.4 (3)° and with the bromo­benzene ring = 20.3 (3)°; dihedral angle between the 2-thienyl and attached phenyl ring = 11.0 (4)°], so that the mol­ecule has a T-shape. In the crystal, supra­molecular chains along the b-axis direction are sustained by C—H⋯S and C—Br⋯π inter­actions. PMID:23723887

  1. 2,3-Dichloro-1,4-hydro­quinone 2,3-dichloro-1,4-benzoquinone monohydrate: a quinhydrone-type 1:1 donor-acceptor [D—A] charge-transfer complex

    PubMed Central

    Guégano, Xavier; Hauser, Jürg; Liu, Shi-Xia; Decurtins, Silvio

    2011-01-01

    In the crystal structure of the title compound (systematic name: 2,3-dichloro­benzene-1,4-diol 2,3-dichloro­cyclo­hexa-2,5-diene-1,4-dione monohydrate), C6H4Cl2O2·C6H2Cl2O2·H2O, the 2,3-dichloro-1,4-hydro­quinone donor (D) and the 2,3-dichloro-1,4-benzoquinone acceptor (A) mol­ecules form alternating stacks along [100]. Their mol­ecular planes [maximum deviations for non-H atoms: 0.0133 (14) (D) and 0.0763 (14) Å (A)] are inclined to one another by 1.45 (3)° and are thus almost parallel. There are π–π inter­actions involving the D and A mol­ecules, with centroid–centroid distances of 3.5043 (9) and 3.9548 (9) Å. Inter­molecular O—H⋯O hydrogen bonds involving the water mol­ecule and the hy­droxy and ketone groups lead to the formation of two-dimensional networks lying parallel to (001). These networks are linked by C—H⋯O inter­actions, forming a three-dimensional structure. PMID:22219991

  2. The conformational energies of 2-methyl- and 4-methyl-1,3-dithiane. The breakdown of 1,3- syn diaxial repulsion hypothesis

    NASA Astrophysics Data System (ADS)

    Ribeiro, Douglas S.; Rittner, Roberto

    2003-09-01

    The conformational enthalpies (Δ H) of 2-methyl- (-1.76 kcal mol -1) and 4-methyl-1,3-dithiane (-1.75 kcal mol -1) were obtained by the analysis of 13C chemical shifts as a function of temperature. These energies are in excellent agreement both with calculated values (B3LYP/6-31G(d,p)) and with literature values based on 2,4-dialkyl-1,3-dithiane. The results confirm the similarity between the conformational energies of the methyl group at the 2 and 4 positions of the dithiane ring and that of methylcyclohexane, despite the larger distances between ring 1,3- syn- axial hydrogens and the closest methyl axial hydrogen in the dithiane ring. The possibility of a buttressing effect on the 2,4-dialkyl-1,3-dithianes previously studied and the rationale of 1,3- syn-axial steric interaction are discussed.

  3. Association of galectin-1 and galectin-3 with Gemin4 in complexes containing the SMN protein.

    PubMed

    Park, J W; Voss, P G; Grabski, S; Wang, J L; Patterson, R J

    2001-09-01

    In previous studies we showed that galectin-1 and galectin-3 are factors required for the splicing of pre-mRNA, as assayed in a cell-free system. Using a yeast two-hybrid screen with galectin-1 as bait, Gemin4 was identified as a putative interacting protein. Gemin4 is one component of a macromolecular complex containing approximately 15 polypeptides, including SMN (survival of motor neuron) protein. Rabbit anti-galectin-1 co-immunoprecipitated from HeLa cell nuclear extracts, along with galectin-1, polypeptides identified to be in this complex: SMN, Gemin2 and the Sm polypeptides of snRNPs. Direct interaction between Gemin4 and galectin-1 was demonstrated in glutathione S-transferase (GST) pull-down assays. We also found that galectin-3 interacted with Gemin4 and that it constituted one component of the complex co-immunoprecipitated with galectin-1. Indeed, fragments of either Gemin4 or galectin-3 exhibited a dominant negative effect when added to a cell-free splicing assay. For example, a dose-dependent inhibition of splicing was observed in the presence of exogenously added N-terminal domain of galectin-3 polypeptide. In contrast, parallel addition of either the intact galectin-3 polypeptide or the C-terminal domain failed to yield the same effect. Using native gel electrophoresis to detect complexes formed by the splicing extract, we found that with addition of the N-terminal domain the predominant portion of the radiolabeled pre-mRNA was arrested at a position corresponding to the H-complex. Inasmuch as SMN-containing complexes have been implicated in the delivery of snRNPs to the H-complex, these results provide strong evidence that galectin-1 and galectin-3, by interacting with Gemin4, play a role in spliceosome assembly in vivo. PMID:11522829

  4. The Synthesis of 1-Phenyl-1,2,3,4-tetrahydroisoquinolines: An Undergraduate Organic Laboratory Experiment and Class Project.

    ERIC Educational Resources Information Center

    Letcher, R. M.; Sammes, M. P.

    1985-01-01

    Describes an undergraduate organic chemistry experiment (requiring three/four 3-hour laboratory sessions) involving a four-stage synthesis of 1-phenyl-1,2,3,4-tetrahydroisoquinolines via the Pictet-Spengler route. In addition, the experiment allows students to study the spectra and properties of aklaloid-like materials while completing several…

  5. 1-(Piperidin-1-yl)-3-(2,4,6-trimethyl-phen-yl)propan-2-ol.

    PubMed

    Maharramov, Abel M; Khalilov, Ali N; Gurbanov, Atash V; Allahverdiyev, Mirze A; Ng, Seik Weng

    2011-01-01

    The title compound, C(17)H(27)NO, features a bufferfly-shaped substituted 2-propanol having an aromatic ring on the 1-carbon and a piperidine ring on the 3-carbon. The piperidine ring adopts a chair conformation and its N atom shows a trigonal coordination. In the crystal, the hy-droxy group inter-acts with the N atom of an inversion-related mol-ecule, generating an O-H⋯N hydrogen-bonded dimer. PMID:21522478

  6. The role of CYP 3A4 and 1A1 in amiodarone-induced hepatocellular toxicity.

    PubMed

    Wu, Qiangen; Ning, Baitang; Xuan, Jiekun; Ren, Zhen; Guo, Lei; Bryant, Matthew S

    2016-06-24

    Amiodarone is a widely used potent antiarrhythmic for the treatment of cardiac disease; however, its use is often discontinued due to numerous adverse effects, including hepatotoxicity. To investigate the role of drug metabolism in this liver toxicity, amiodarone and its major metabolite desethylamiodarone were incubated with HepG2 cells overexpressing a series of cytochrome P450 (CYP) isoforms. Significantly higher cytotoxicity of amiodarone was observed in HepG2 cells overexpressing CYP3A4 or CYP1A1, compared with that observed in empty vector transduced control cells. Further, higher levels of the more potent hepatotoxic metabolite desethylamiodarone were detected in CYP3A4 or CYP1A1 expressed cells. The CYP3A4 inhibitor ketoconazole and the CYP1A1 inhibitor α-naphthoflavone drastically inhibited the metabolism of amiodarone to desethylamiodarone. Along with the inhibition of CYP1A1 or CYP3A4, the cytotoxicity of amiodarone was significantly reduced. These data indicate that the metabolism of amiodarone to desethylamiodarone by CYP1A1 or CYP3A4 plays an important role in the hepatocellular toxicity of amiodarone. PMID:27113703

  7. Molecular structure of 4-methoxy-2,3-dimethyl-2,4-dihydro[1,2]benzoxaphosphinino-[4,3- c]pyrazole-4-oxide and its carboxylic analogues

    NASA Astrophysics Data System (ADS)

    Małecka, Magdalena; Massa, Werner; Harms, Klaus; Budzisz, Elżbieta

    2005-03-01

    The crystal structures of 5a 4-methoxy-2,3-dimethyl-2,4-dihydro[1,2]benzoxaphosphinino-[4,3- c]pyrazole-4-oxide and 5b 2,3-dimethyl[1]benzopyrano[4,3- c]pyrazol-4-one have been determined by 31P and 1H NMR study and single-crystal X-ray diffraction. The progress of conversion of chromone 1a was monitored by 31P NMR. After 24 h two additional signals of 4a and 5a could be seen in NMR spectrum. Both compounds crystallise in monoclinic system in space group P2 1/c . The crystal data are: 5aa=10.306(1), b=11.875(1), c=11.221(1) Å, β=112.992(7)°, Z=4; 5ba=7.386(1), b=17.094(2), c=8.557(1) Å, β=114.208(9)°, Z=4. The structure of 5a contains methanol disordered over a centre of symmetry. The crystal of 5b was twinned.

  8. Characteristics of nitrogen release from synthetic zeolite Na-P1 occluding NH4NO3.

    PubMed

    Park, Man; Kim, Jong Su; Choi, Choong Lyeal; Kim, Jang-Eok; Heo, Nam Ho; Komarneni, Sridhar; Choi, Jyung

    2005-08-18

    Zeolites can accommodate a considerable amount of occluded salt such as NH4NO3, which can serve as a good source of slow-release plant nutrient. This study evaluates the kinetics of ion release from NH4NO3-occluded Na-P1 (N-NaP) using a simulated soil solution and deionized water as leaching solutions. The patterns of ion releases were examined as a function of leaching time under both static and continuous-flow conditions for more than one month. Releases of both NH4+ and NO3- from N-NaP were found to be slow and steady under both the above conditions. The soil solution affected the release of NH4+ and NO3- differently, while deionized water released nearly the same equivalents of these ions. This clearly indicates that ion release from salt-occluded zeolite involves two different reactions, cation exchange and dissolution. The kinetics of ion release from occluded NH4NO3 under static condition was best described by the standard Elovich model while the power function model best expressed these under continuous-flow condition. The initial ion release patterns under both conditions exhibited considerable deviation from the simulated models, probably as a result of the presence of hydrated occluded NH4NO3. Flow condition and the presence of electrolytes in leaching solution affected the release kinetics significantly. Release of occluded NH4NO3 was delayed by the presence of the NH4NO3 coated on zeolite crystals. These results indicate that the ion release property of occluded salt could be predicted and controlled. This study clearly shows that NH4NO3-occluded zeolites could be developed as slow release fertilizers. PMID:15963593

  9. Organocatalytic Synthesis of Fused Bicyclic 2,3-Dihydro-1,3,4-oxadiazoles through an Intramolecular Cascade Cyclization.

    PubMed

    Fugard, Alison J; Thompson, Bethany K; Slawin, Alexandra M Z; Taylor, James E; Smith, Andrew D

    2015-12-01

    Hydrazone-carboxylic acids undergo intramolecular cyclization in the presence of pivaloyl chloride, iPr(2)NEt, and catalytic DABCO to form a range of substituted fused tricyclic 2,3-dihydro-1,3,4-oxadiazoles in high yields. PMID:26598296

  10. Enzymatic Analysis of PTEN Ubiquitylation by WWP2 and NEDD4-1 E3 Ligases.

    PubMed

    Chen, Zan; Thomas, Stefani N; Bolduc, David M; Jiang, Xuejun; Zhang, Xiangbin; Wolberger, Cynthia; Cole, Philip A

    2016-07-01

    PTEN is a lipid phosphatase that converts phosphatidylinositol 3,4,5-phosphate (PIP3) to phosphatidylinositol 4,5-phosphate (PIP2) and plays a critical role in the regulation of tumor growth. PTEN is subject to regulation by a variety of post-translational modifications, including phosphorylation on a C-terminal cluster of four Ser/Thr residues (380, 382, 383, and 385) and ubiquitylation by various E3 ligases, including NEDD4-1 and WWP2. It has previously been shown that C-terminal phosphorylation of PTEN can increase its cellular half-life. Using in vitro ubiquitin transfer assays, we show that WWP2 is more active than NEDD4-1 in ubiquitylating unphosphorylated PTEN. The mapping of ubiquitylation sites in PTEN by mass spectrometry showed that both NEDD4-1 and WWP2 can target a broad range of Lys residues in PTEN, although NEDD4-1 versus WWP2 showed a stronger preference for ubiquitylating PTEN's C2 domain. Whereas tetraphosphorylation of PTEN did not significantly affect its ubiquitylation by NEDD4-1, it inhibited PTEN ubiquitylation by WWP2. Single-turnover and pull-down experiments suggested that tetraphosphorylation of PTEN appears to weaken its interaction with WWP2. These studies reveal how the PTEN E3 ligases WWP2 and NEDD4-1 exhibit distinctive properties in Lys selectivity and sensitivity to PTEN phosphorylation. Our findings also provide a molecular mechanism for the connection between PTEN Ser/Thr phosphorylation and PTEN's cellular stability. PMID:27295432

  11. (E)-1-(3-Bromo­phen­yl)-3-(3,4-dimeth­oxy­phen­yl)prop-2-en-1-one

    PubMed Central

    Escobar, Carlos A.; Trujillo, Alexander; Howard, Judith A. K.; Fuentealba, Mauricio

    2012-01-01

    The mol­ecular structure of the title compound, C17H15BrO3, consists of a bromo­phenyl and a 3,4-dimeth­oxy­phenyl group linked through a prop-2-en-1-one spacer. The C=C double bond displays an E conformation, while the carbonyl group shows an S-cis conformation relative to the double bond. PMID:22412737

  12. NAD+-SIRT1 control of H3K4 trimethylation through circadian deacetylation of MLL1

    PubMed Central

    Aguilar-Arnal, Lorena; Katada, Sayako; Orozco-Solis, Ricardo

    2015-01-01

    The circadian clock controls the transcription of hundred genes through specific chromatin remodeling events. The histone methyltransferase Mixed-Lineage Leukemia 1 (MLL1) coordinates recruitment of CLOCK–BMAL1 activator complexes to chromatin, an event associated to cyclic H3K4 tri-methylation at circadian promoters. Remarkably, in mouse liver circadian H3K4me3 is modulated by SIRT1, a NAD+ dependent deacetylase involved in clock control. We show that mammalian MLL1 is acetylated at two conserved residues, K1130 and K1133. Notably, MLL1 acetylation is cyclic, controlled by the clock and by SIRT1, and impacts the methyltransferase activity of MLL1. Moreover, H3K4 methylation at clock-controlled gene promoters is influenced by pharmacological or genetic inactivation of SIRT1. Finally, MLL1 acetylation and H3K4me3 levels at circadian gene promoters depend on NAD+ circadian levels. These findings reveal a previously unappreciated regulatory pathway between energy metabolism and histone methylation. PMID:25751424

  13. The Reaction of DABCO with 4-Chloro-5H-1,2,3-dithiazoles: Synthesis and Chemistry of 4-[N-(2-Chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazoles.

    PubMed

    Koyioni, Maria; Manoli, Maria; Koutentis, Panayiotis A

    2016-01-15

    N-(4-Chloro-5H-1,2,3-dithiazol-5-ylidene)anilines react with DABCO in hot PhCl to give N-{4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazol-5-ylidene}anilines in high yields (70-92%). The reaction also works with 4-chloro-5H-1,2,3-dithiazol-5-one and -thione, giving the corresponding products in 85% and 76% yields, respectively. While the reaction of several (4-chloro-5H-1,2,3-dithiazol-5-ylidene)methanes with DABCO failed to give {4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazol-5-ylidene}methanes, these can be prepared in moderate yields via classical cycloaddition-retrocycloaddition strategies from 4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazole-5-thione. The 2-chloroethyl moiety on selected dithiazoles was also modified without cleavage of the 1,2,3-dithiazole by reaction with various nucleophiles, giving access to 4-[N-(2-substituted)piperazin-1-yl]-5H-1,2,3-dithiazoles in moderate to high yields. PMID:26671065

  14. Crystal structure of 4-(4-meth-oxy-phen-yl)-4',4'-dimethyl-3-p-tolyl-3',4'-di-hydro-1'H,3H-spiro-[isoxazole-5,2'-naphthalen]-1'-one.

    PubMed

    Akhazzane, Mohamed; Al Houari, Ghali; El Yazidi, Mohamed; Saadi, Mohamed; El Ammari, Lahcen

    2015-12-01

    In the title compound, C28H27NO3, the cyclo-hexa-none and isoxazole rings have envelope conformations, with the methyl-ene and spiro C atoms as the flaps, respectively. The mean plane of the isoxazole ring is inclined slightly to the p-tolyl ring, making a dihedral angle of 14.20 (9)°, and is nearly perpendicular to the mean plane through the tetra-lone moiety and to the meth-oxy-phenyl ring [dihedral angles = 83.41 (8) and 72.12 (9)°, respectively]. The crystal packing is stabilized mainly by van der Waals forces. PMID:26870562

  15. Vibrational signatures of hydrogen bonding in the protonated ammonia clusters NH4+(NH3)1-4

    NASA Astrophysics Data System (ADS)

    Yang, Y.; Kühn, O.; Santambrogio, G.; Goebbert, D. J.; Asmis, K. R.

    2008-12-01

    The gas phase vibrational spectroscopy of the protonated ammonia dimer N2H7+, a prototypical system for strong hydrogen bonding, is studied in the spectral region from 330 to 1650 cm-1 by combining infrared multiple photon dissociation and multidimensional quantum mechanical simulations. The fundamental transition of the antisymmetric proton stretching vibration is observed at 374 cm-1 and assigned on the basis of a six-dimensional model Hamiltonian, which predicts this transition at 471 cm-1. Photodissociation spectra of the larger protonated ammonia clusters NH4+(NH3)n with n =2-4 are also reported for the range from 1050 to 1575 cm-1. The main absorption features can be assigned within the harmonic approximation, supporting earlier evidence that hydrogen bonding in these clusters is considerably weaker than for n =1.

  16. Novel PARP-1 inhibitors based on a 2-propanoyl-3H-quinazolin-4-one scaffold.

    PubMed

    Giannini, Giuseppe; Battistuzzi, Gianfranco; Vesci, Loredana; Milazzo, Ferdinando M; De Paolis, Francesca; Barbarino, Marcella; Guglielmi, Mario Berardino; Carollo, Valeria; Gallo, Grazia; Artali, Roberto; Dallavalle, Sabrina

    2014-01-15

    Poly(ADP-ribose)polymerase-I (PARP-1) enzyme is involved in maintaining DNA integrity and programmed cell death. A virtual screening of commercial libraries led to the identification of five novel scaffolds with inhibitory profile in the low nanomolar range. A hit-to-lead optimization led to the identification of a group of new potent PARP-1 inhibitors, acyl-piperazinylamides of 3-(4-oxo-3,4-dihydro-quinazolin-2-yl)-propionic acid. Molecular modeling studies highlighted the preponderant role of the propanoyl side chain. PMID:24388690

  17. Carcinogenicity and DNA adduct formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and enantiomers of its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in F-344 rats.

    PubMed

    Balbo, Silvia; Johnson, Charles S; Kovi, Ramesh C; James-Yi, Sandra A; O'Sullivan, M Gerard; Wang, Mingyao; Le, Chap T; Khariwala, Samir S; Upadhyaya, Pramod; Hecht, Stephen S

    2014-12-01

    4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is metabolized to enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), found in the urine of virtually all people exposed to tobacco products. We assessed the carcinogenicity in male F-344 rats of (R)-NNAL (5 ppm in drinking water), (S)-NNAL (5 ppm), NNK (5 ppm) and racemic NNAL (10 ppm) and analyzed DNA adduct formation in lung and pancreas of these rats after 10, 30, 50 and 70 weeks of treatment. All test compounds induced a high incidence of lung tumors, both adenomas and carcinomas. NNK and racemic NNAL were most potent; (R)-NNAL and (S)-NNAL had equivalent activity. Metastasis was observed from primary pulmonary carcinomas to the pancreas, particularly in the racemic NNAL group. DNA adducts analyzed were O (2)-[4-(3-pyridyl)-4-oxobut-1-yl]thymidine (O (2)-POB-dThd), 7-[4-(3-pyridyl)-4-oxobut-1-yl]guanine(7-POB-Gua),O (6)-[4-(3-pyridyl)-4-oxobut-1-yl]deoxyguanosine(O (6)-POB-dGuo),the 4-(3-pyridyl)-4-hydroxybut-1-yl(PHB)adductsO (2)-PHB-dThd and 7-PHB-Gua, O (6)-methylguanine (O (6)-Me-Gua) and 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing adducts. Adduct levels significantly decreased with time in the lungs of rats treated with NNK. Pulmonary POB-DNA adducts and O (6)-Me-Gua were similar in rats treated with NNK and (S)-NNAL; both were significantly greater than in the (R)-NNAL rats. In contrast, pulmonary PHB-DNA adduct levels were greatest in the rats treated with (R)-NNAL. Total pulmonary DNA adduct levels were similar in (S)-NNAL and (R)-NNAL rats. Similar trends were observed for DNA adducts in the pancreas, but adduct levels were significantly lower than in the lung. The results of this study clearly demonstrate the potent pulmonary carcinogenicity of both enantiomers of NNAL in rats and provide important new information regarding DNA damage by these compounds in lung and pancreas. PMID:25269804

  18. Solvent Effects on Molecular Aggregation in 4-(5-Heptyl-1,3,4-thiadiazol-2-yl)benzene-1,3-diol and 4-(5-Methyl-1,3,4-thiadiazol-2-yl)benzene-1,3-diol.

    PubMed

    Matwijczuk, Arkadiusz; Kluczyk, Dariusz; Górecki, Andrzej; Niewiadomy, Andrzej; Gagoś, Mariusz

    2016-08-18

    The article presents the results of spectroscopic studies of 4-(5-methyl-1,3,4-thiadiazol-2-yl)benzene-1,3-diol (C1) and 4-(5-heptyl-1,3,4-thiadiazol-2-yl)benzene-1,3-diol (C7) in organic solvent solutions. Depending on the concentration of the compound used, three bands were observed in the fluorescence emission spectra of the compounds in DMSO solutions. A single band was observed in methanol, propan-2-ol, or ethanol. The significantly shortened fluorescence lifetimes and the different shapes of circular dichroism (CD) spectra clearly indicate association of the fluorescence effects with the aggregation processes in the analyzed compounds. The differences in the course of the CD spectra also imply an effect of the substituent group structure on the molecule aggregation interactions. Therefore, it has been postulated that the occurrence of the different spectral forms induced by changes in the compound concentration may be related to the aggregation effects of C1 and C7 molecules, which are also induced by differences in the alkyl substituent structure. PMID:27454065

  19. Rotational spectrum, conformation and dipole moment of 4-methyl-1,3-dioxane

    NASA Astrophysics Data System (ADS)

    Shapkin, A. A.; Galeev, R. V.; Gunderova, L. N.; Fayzullin, M. G.; Mamleev, A. H.

    2006-12-01

    The rotational spectrum of 4-methyl-1,3-dioxane, C 5H 100 II, has been recorded from 16.0 to 40.0 GHz. The a-, b- and C- type transitions with J<=57 have been observed and assigned for the normal species in the ground vibrational state. The rotational constants and the quartic centrifugal distortion constants were determined to be A = 4802.335(2) MHz, B = 2376.163(1) MHz, C = 1738.852(1) MHz and Δ J = 0.1496(6) kHz, Δ JK = 0.157(5) kHz, Δ K = 0.76(3) kHz, δJ = 0.0423(1) kHz, δK 0.260(3) kHz. Stark effect measurements were used to determine the projections of the dipole moment on the principal inertial axes (in Debye units): μ a = 0.73(1), μ b = 1.32(1), c = 1.36(1) and μ tot = 2.03(2). Comparison of the experimental rotational constants and dipole moment components with results of ab initio calculations (B3PW91/aug-cc-pVDZ) shown that 4-methyl-l,3-dioxane exist in chair form with equatorial orientation of methyl group.

  20. Crystal structure of (Z)-1-(3,4-dichlorophenyl)-3-methyl-4-[(naphthalen-1-yl-amino)(p-tolyl)methylidene]-1H-pyrazol-5(4H)-one.

    PubMed

    Sharma, Naresh; Parihar, Sanjay; Jadeja, R N; Kant, Rajni; Gupta, Vivek K

    2014-09-01

    The title Schiff base compound, C28H21Cl2N3O, was synthesized by the condensation of 1-(3,4-di-chloro-phen-yl)-3-methyl-4-(4-methyl-benzo-yl)-1H-pyrazol-5(4H)-one with 1-aminona-phthalene. The p-tolyl ring is normal to the pyrazole ring, with a dihedral angle of 88.02 (14)°, and inclined to the naphthalene ring system by 78.60 (12)°. The pyrazole ring is inclined to the naphthalene ring system and the di-chloro-substituted benzene ring by 63.30 (12) and 11.03 (13)°, respectively. The amino group and carbonyl oxygen atom are involved in an intra-molecular N-H⋯O hydrogen bond enclosing an S(6) ring motif. There is also a short C-H⋯O contact involving the carbonyl O atom and the adjacent benzene ring. In the crystal, mol-ecules are linked by C-H⋯π inter-actions, forming a three-dimensional structure. PMID:25309277

  1. 40 CFR 721.8950 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Chromate(3-), bis phenyl]sulfonyl... Significant New Uses for Specific Chemical Substances § 721.8950 Chromate(3-), bis phenyl]sulfonyl]amino]-4... substance identified as chromate(3-), bis...

  2. 40 CFR 721.8950 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Chromate(3-), bis phenyl]sulfonyl... Significant New Uses for Specific Chemical Substances § 721.8950 Chromate(3-), bis phenyl]sulfonyl]amino]-4... substance identified as chromate(3-), bis...

  3. 40 CFR 721.8950 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Chromate(3-), bis phenyl]sulfonyl... Significant New Uses for Specific Chemical Substances § 721.8950 Chromate(3-), bis phenyl]sulfonyl]amino]-4... substance identified as chromate(3-), bis...

  4. Histamine H1, H3 and H4 receptors are involved in pruritus.

    PubMed

    Rossbach, K; Nassenstein, C; Gschwandtner, M; Schnell, D; Sander, K; Seifert, R; Stark, H; Kietzmann, M; Bäumer, W

    2011-09-01

    Histamine has long been recognised as a classical inducer of pruritus. However, the specific mechanism of histamine-induced itch has still not been fully understood. The H1 and H4 receptor appear to be key components in the induction of itch. The specific role of the H3 receptor in histamine-induced itch remains unclear. The aim of our study was to investigate the role of the four known histamine receptors (H1-4) in acute itch in mice. Intradermal injection of the selective H3R inverse agonist pitolisant induced strong itch in mice. Pitolisant (50 nmol/injection)-induced pruritus could be completely blocked by a combined treatment with the H1R antagonist cetirizine (15 mg/kg) and the H4R antagonist JNJ 7777120 (15 mg/kg), whereas the H2R antagonist ranitidine (15 mg/kg) failed to inhibit the scratch response. Next, expression and function of histamine receptors on sensory neurons isolated from dorsal root ganglia of mice were investigated. As the itch sensation results from the excitation of sensory nerves in the skin, we further focused on skin specific sensory neurons. Therefore, neurons were retrograde labelled from the skin by means of a fluorescent tracer. Expression of H1R, H3R and H4R on skin innervating sensory neurons was detected. By single-cell calcium imaging, it was demonstrated that histamine induces a calcium increase in a subset of (skin-specific) sensory neurons via activation of the H1R and H4R as well as inhibition of the H3R. It is assumed that the decreased threshold in response to H3R antagonism activates H1R and H4R on sensory neurons, which in turn results in the excitation of histamine-sensitive afferents and therefore elicits the sensation of itch. PMID:21689731

  5. Recruitment of PI4KIIIβ to Coxsackievirus B3 Replication Organelles Is Independent of ACBD3, GBF1, and Arf1

    PubMed Central

    Dorobantu, Cristina M.; van der Schaar, Hilde M.; Ford, Lauren A.; Strating, Jeroen R. P. M.; Ulferts, Rachel; Fang, Ying; Belov, George

    2014-01-01

    ABSTRACT Members of the Enterovirus (poliovirus [PV], coxsackieviruses, and human rhinoviruses) and Kobuvirus (Aichi virus) genera in the Picornaviridae family rely on PI4KIIIβ (phosphatidylinositol-4-kinase IIIβ) for efficient replication. The small membrane-anchored enteroviral protein 3A recruits PI4KIIIβ to replication organelles, yet the underlying mechanism has remained elusive. Recently, it was shown that kobuviruses recruit PI4KIIIβ through interaction with ACBD3 (acyl coenzyme A [acyl-CoA]-binding protein domain 3), a novel interaction partner of PI4KIIIβ. Therefore, we investigated a possible role for ACBD3 in recruiting PI4KIIIβ to enterovirus replication organelles. Although ACBD3 interacted directly with coxsackievirus B3 (CVB3) 3A, its depletion from cells by RNA interference did not affect PI4KIIIβ recruitment to replication organelles and did not impair CVB3 RNA replication. Enterovirus 3A was previously also proposed to recruit PI4KIIIβ via GBF1/Arf1, based on the known interaction of 3A with GBF1, an important regulator of secretory pathway transport and a guanine nucleotide exchange factor (GEF) of Arf1. However, our results demonstrate that inhibition of GBF1 or Arf1 either by pharmacological inhibition or depletion with small interfering RNA (siRNA) treatment did not affect the ability of 3A to recruit PI4KIIIβ. Furthermore, we show that a 3A mutant that no longer binds GBF1 was capable of recruiting PI4KIIIβ, even in ACBD3-depleted cells. Together, our findings indicate that unlike originally envisaged, coxsackievirus recruits PI4KIIIβ to replication organelles independently of ACBD3 and GBF1/Arf1. IMPORTANCE A hallmark of enteroviral infection is the generation of new membranous structures to support viral RNA replication. The functionality of these “replication organelles” depends on the concerted actions of both viral nonstructural proteins and co-opted host factors. It is thus essential to understand how these structures are

  6. Unprecedented Intramolecular [4 + 2]-Cycloaddition between a 1,3-Diene and a Diazo Ester.

    PubMed

    Qiu, Huang; Srinivas, Harathi D; Zavalij, Peter Y; Doyle, Michael P

    2016-02-17

    Diazo compounds that are well-known to undergo [3 + 2]-cycloaddition provide the first examples of the previously unknown [4 + 2]-cycloaddition with dienes that occur thermally under mild conditions and in high yields. Reactions are initiated from reactants prepared from propargyl aryldiazoacetates that undergo gold(I)-catalyzed rearrangement to activated 1,3-dienyl aryldiazoacetates. These reactions proceed to mixtures of both [4 + 2]-cycloaddition and the 1,3-dienyl aryldiazoacetate after long reaction times. At short reaction times, however, both E- and Z-1,3-dienyl aryldiazoacetates are formed and, after isolation, thermal reactions with the E-isomers form the products from [4 + 2]-cycloaddition with ΔH(‡)298 = 15.6 kcal/mol and ΔS(‡)298 = -27.3 cal/(mol·°C). The Z-isomer is inert to [4 + 2]-cycloaddition under these conditions. The Hammett relationships from aryl-substituted diazo esters (ρ = +0.89) and aryl-substituted dienes (ρ = -1.65) are consistent with the dipolar nature of this transformation. PMID:26794409

  7. Discovery of N-(3-fluoro-4-methylsulfonamidomethylphenyl)urea as a potent TRPV1 antagonistic template.

    PubMed

    Ann, Jihyae; Sun, Wei; Zhou, Xing; Jung, Aeran; Baek, Jisoo; Lee, Sunho; Kim, Changhoon; Yoon, Suyoung; Hong, Sunhye; Choi, Sun; Turcios, Noe A; Herold, Brienna K A; Esch, Timothy E; Lewin, Nancy E; Abramovitz, Adelle; Pearce, Larry V; Blumberg, Peter M; Lee, Jeewoo

    2016-08-01

    A series of homologous analogues of prototype antagonist 1 and its urea surrogate were investigated as hTRPV1 ligands. Through one-carbon elongation in the respective pharmacophoric regions, N-(3-fluoro-4-methylsulfonamidomethylphenyl)urea was identified as a novel and potent TRPV1 antagonistic template. Its representative compound 27 showed a potency comparable to that of lead compound 1. Docking analysis of compound 27 in our hTRPV1 homology model indicated that its binding mode was similar with that of 1S. PMID:27317643

  8. Crystal structure of 1-benzyl-4-formyl-1H-pyrrole-3-carb-oxamide.

    PubMed

    Zhong, Qi-Di; Hu, Sheng-Quan; Yan, Hong

    2016-02-01

    In the title compound, C13H12N2O2 (I), the mean planes of the pyrrole and benzyl rings are approximately perpendicular, forming a dihedral angle of 87.07 (4) °. There is an intra-molecular N-H⋯O hydrogen bond forming an S(7) ring motif. In the crystal, mol-ecules are linked via a pair of N-H⋯O hydrogen bonds forming inversion dimers. C-H⋯O hydrogen bonds link the dimers into chains along direction [10-1]. The chains are further linked by weak C-H⋯π inter-actions forming layers parallel to the ac plane. PMID:26958371

  9. Functionalized Congeners of 1,4-Dihydropyridines as Antagonist Molecular Probes for A3 Adenosine Receptors

    PubMed Central

    Li, An-Hu; Chang, Louis; Ji, Xiao-duo; Melman, Neli; Jacobson, Kenneth A.

    2012-01-01

    4-Phenylethynyl-6-phenyl-1,4-dihydropyridine derivatives are selective antagonists at human A3 adenosine receptors, with Ki values in a radioligand binding assay vs [125I]AB-MECA [N6-(4-amino-3-iodobenzyl)-5′-N-methylcarbamoyl-adenosine] in the submicromolar range. In this study, functionalized congeners of 1,4-dihydropyridines were designed as chemically reactive adenosine A3 antagonists, for the purpose of synthesizing molecular probes for this receptor subtype. Selectivity of the new analogues for cloned human A3 adenosine receptors was determined in radioligand binding in comparison to binding at rat brain A1 and A2A receptors. Benzyl ester groups at the 3- and/or 5-positions and phenyl groups at the 2- and/or 6-positions were introduced as potential sites for chain attachment. Structure–activity analysis at A3 adenosine receptors indicated that 3,5-dibenzyl esters, but not 2,6-diphenyl groups, are tolerated in binding. Ring substitution of the 5-benzyl ester with a 4-fluorosulfonyl group provided enhanced A3 receptor affinity resulting in a Ki value of 2.42 nM; however, a long-chain derivative containing terminal amine functionalization at the 4-position of the 5-benzyl ester showed only moderate affinity. This sulfonyl fluoride derivative appeared to bind irreversibly to the human A3 receptor (1 h incubation at 100 nM resulting in the loss of 56% of the specific radioligand binding sites), while the binding of other potent dihydropyridines and other antagonists was generally reversible. At the 3-position of the dihydropyridine ring, an amine-functionalized chain attached at the 4-position of a benzyl ester provided higher A3 receptor affinity than the corresponding 5-position isomer. This amine congener was also used as an intermediate in the synthesis of a biotin conjugate, which bound to A3 receptors with a Ki value of 0.60 μM. PMID:10411465

  10. Synthesis of [1,2-3H2]cholecalciferol and metabolism of [4-14C,1,2-3H2]- and [4-14C,1-3H]-cholecalciferol in rachitic rats and chicks

    PubMed Central

    Lawson, D. E. M.; Pelc, B.; Bell, P. A.; Wilson, P. W.; Kodicek, E.

    1971-01-01

    [1,2-3H2]Cholecalciferol has been synthesized with a specific radioactivity of 508mCi/mmol by using tristriphenylphosphinerhodium chloride, the homogeneous hydrogen catalyst. With doses of 125ng (5i.u.) of [4-14C,1-3H2]cholecalciferol the tissue distribution in rachitic rats of cholecalciferol and its metabolites (25-hydroxycholecalciferol and peak P material) was similar to that found in chicken with 500ng doses of the double-labelled vitamin. The only exceptions were rat kidney, with a very high concentration of vitamin D, and rat blood, with a higher proportion of peak P material, containing a substance formed from vitamin D with the loss of hydrogen from C-1. Substance P formed from [4-14C,1,2-3H2]cholecalciferol retained 36% of 3H, the amount expected from its distribution between C-1 and C-2, the 3H at C-1 being lost. 25-Hydroxycholecalciferol does not seem to have any specific intracellular localization within the intestine of rachitic chicks. The 3H-deficient substance P was present in the intestine and bone 1h after a dose of vitamin D and 30min after 25-hydroxycholecalciferol. There was very little 25-hydroxycholecalciferol in intestine at any time-interval, but bone and blood continued to take it up over the 8h experimental period. It is suggested that the intestinal 3H-deficient substance P originates from outside this tissue. The polar metabolite found in blood and which has retained its 3H at C-1 is not a precursor of the intestinal 3H-deficient substance P. PMID:4329870

  11. A facile synthesis of new 1,2-dihydro-2 lambda(5)-[1,3]oxazolo[5,4-d][1,3,2]diazaphosphinine derivatives starting from 2-benzoylamino-3,3-dichloroacrylonitrile

    SciTech Connect

    Gakh, Andrei A; Shablykin, Oleg V

    2008-06-01

    Easily accessible 2-benzoylamino-3,3-dichloroacrylonitrile, when treated successively with primary amines, phosphorus pentachloride, sulfur dioxide, and various N- or S-nucleophiles, furnishes the corresponding derivatives of 1,2-dihydro-2{lambda}{sup 5}-[1,3]oxazolo[5,4-d][1,3,2]diazaphosphinine, a novel fused heterocycle. The structure of the compounds obtained is unequivocally confirmed by spectroscopic methods and X-ray diffraction analysis.

  12. 40 CFR 721.5262 - 2,7-Naphthalenedisulfonic acid, 5-[[4-chloro-6-[substituted] amino]-1,3,5-triazin-2-yl]amino]-4...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...,7-Naphthalenedisulfonic acid, 5- amino]-1,3,5-triazin-2-yl]amino]-4-hydroxy-3- -, trisodium salt...-Naphthalenedisulfonic acid, 5- amino]-1,3,5-triazin-2-yl]amino]-4-hydroxy-3- -, trisodium salt (PMN P-00-0803) is...-naphthalenedisulfonic acid, 5- ethyl]amino]-1,3,5-triazin-2-yl]amino]-4-hydroxy-3- -, sodium salt (1:3) (PMN......

  13. High nitrogen explosives. Part 2. Dibenzo-1,3a,4,6a-tetraazapentalenes and benzo-1 2,3,4-tetrazine-1,3-dioxides. Progress report, February 1994-June 1995

    SciTech Connect

    Altmann, K.L.; Merwin, L.H.; Norris, W.P.; Wilson, W.S.; Gilardi, R.

    1996-08-01

    High nitrogen materials are sought as a potentially dense, powerful but insensitive explosive and propellant ingredients. Elucidation of the structure and chemistry of dibenzo-1 ,3a,4,6a-tetraazapentalenes has continued, with particular attention to a putative C12N12O12 derivative initially prepared at the University of New Orleans. This research contributed substantially to identification of the actual o-quinone hydrate structure, and explanation of the apparently anomalous explosive insensitivity of the material. Synthesis of the novel 5,7-dinitrobenzo-1, 2,3,4-tetrazine-1,3-dioxide has been repeated, its structure has been confirmed, and preliminary evaluation of its explosive sensitivity has been completed.

  14. Alum Catalyzed Simple, Efficient, and Green Synthesis of 2-[3-Amino-5-methyl-5-(pyridin-3-yl)-1,5-dihydro-4H-1,2,4-triazol-4-yl]propanoic Acid Derivatives in Aqueous Media

    PubMed Central

    Sachdeva, Harshita; Dwivedi, Diksha; Saroj, Rekha

    2013-01-01

    Alum (KAl(SO4)2·12H2O) is an inexpensive, efficient, and nontoxic catalyst used for the synthesis of 2-[3-amino-5-methyl-5-(pyridin-3-yl)-1,5-dihydro-4H-1,2,4-triazol-4-yl]propanoic acid derivatives in aqueous media by the reaction of 3-acetyl pyridine (1), amino acids (2)/(6), and thiosemicarbazide (4) at 80°C. This methodology offers significant improvements for the synthesis of products with regards to the yield of products, simplicity in operation, and green aspects by avoiding toxic catalysts which uphold the motto of green chemistry. Synthesized compounds have been characterized by FT-IR, 13C NMR, and 1HNMR spectroscopy. PMID:24288503

  15. Upregulation of the E3 ligase NEDD4-1 by Oxidative Stress Degrades IGF-1 Receptor Protein in Neurodegeneration

    PubMed Central

    Kwak, Young-Don; Wang, Bin; Li, Jing Jing; Wang, Ruishan; Deng, Qiyue; Diao, Shiyong; Chen, Yaomin; Xu, Raymond; Masliah, Eliezer; Xu, Huaxi; Sung, Jung-Joon

    2012-01-01

    The importance of ubiquitin E3 ligases in neurodegeneration is being increasingly recognized. The crucial role of NEDD4-1 in neural development is well appreciated; however, its role in neurodegeneration remains unexplored. Herein, we report increased NEDD4-1 expression in the degenerated tissues of several major neurodegenerative diseases. Moreover, its expression is upregulated in cultured neurons in response to various neurotoxins, including zinc and hydrogen superoxide, via transcriptional activation likely mediated by the reactive oxygen species (ROS)-responsive FOXM1B. Reduced protein levels of the insulin-like growth factor receptor (IGF-1Rβ) were observed as a consequence of upregulated NEDD4-1 via the ubiquitin-proteasome system. Overexpression of a familial mutant form of superoxide dismutase 1 (SOD1) (G93A) in neuroblastoma cells resulted in a similar reduction of IGF-1Rβ protein. This inverse correlation between NEDD4-1 and IGF-1Rβ was also observed in the cortex and spinal cords of mutant (G93A) SOD1 transgenic mice at a presymptomatic age, which was similarly induced by in vivo-administered zinc in wild-type C57BL/6 mice. Furthermore, histochemistry reveals markedly increased NEDD4-1 immunoreactivity in the degenerating/degenerated motor neurons in the lumbar anterior horn of the spinal cord, suggesting a direct causative role for NEDD4-1 in neurodegeneration. Indeed, downregulation of NEDD4-1 by shRNA or overexpression of a catalytically inactive form rescued neurons from zinc-induced cell death. Similarly, neurons with a NEDD4-1 haplotype are more resistant to apoptosis, largely due to expression of higher levels of IGF-1Rβ.Together, our work identifies a novel molecular mechanism for ROS-upregulated NEDD4-1 and the subsequently reduced IGF-1Rβ signaling in neurodegeneration. PMID:22875931

  16. Crystal structure of 4-[benzylideneamino]-3-thiophen-2-yl-methyl-4,5-dihydro-1H-[1,2,4] triazole-5-one

    SciTech Connect

    Tanak, H.

    2013-12-15

    The crystal structure of the title compound C{sub 14}H{sub 12}N{sub 4}OS was determined by the X-ray diffraction method. The compound crystallizes in the triclinic space group P-bar1 with Z = 2. The molecule is not planar: the dihedral angle between the triazole and thiophene rings is 73.98(2)°, and that between the triazole and benzene rings is 4.05(2)°. The thiophene ring is disordered over two positions, which are approximately parallel and oppositely oriented. The major component refined to a site-occupancy factor of 0.573(3). An intramolecular C-H...O hydrogen bond generates an S(6) ring motif. In the crystal, molecules are linked together by two pairs of N-H...O interactions (to the same O atom as acceptor), forming inversion dimers. The crystal packing is also stabilized by π-π interactions [centroid-centroid distance is 3.978 Å].

  17. Optimization of pyrazole-containing 1,2,4-triazolo-[3,4-b]thiadiazines, a new class of STAT3 pathway inhibitors.

    PubMed

    LaPorte, Matthew G; Wang, Zhuzhu; Colombo, Raffaele; Garzan, Atefeh; Peshkov, Vsevolod A; Liang, Mary; Johnston, Paul A; Schurdak, Mark E; Sen, Malabika; Camarco, Daniel P; Hua, Yun; Pollock, Netanya I; Lazo, John S; Grandis, Jennifer R; Wipf, Peter; Huryn, Donna M

    2016-08-01

    Structure-activity relationship studies of a 1,2,4-triazolo-[3,4-b]thiadiazine scaffold, identified in an HTS campaign for selective STAT3 pathway inhibitors, determined that a pyrazole group and specific aryl substitution on the thiadiazine were necessary for activity. Improvements in potency and metabolic stability were accomplished by the introduction of an α-methyl group on the thiadiazine. Optimized compounds exhibited anti-proliferative activity, reduction of phosphorylated STAT3 levels and effects on STAT3 target genes. These compounds represent a starting point for further drug discovery efforts targeting the STAT3 pathway. PMID:27381083

  18. Synthesis, infrared spectral studies and theoretical calculations of 4-phenyl-4,5-dihydrobenzo[ f][1,4]oxazepin-3(2 H)-one (thione)

    NASA Astrophysics Data System (ADS)

    Agirbas, Hikmet; Sagdinc, Seda; Kandemirli, Fatma; Kemal, Berat

    2008-12-01

    Salicylaldehyde (1) was reacted with aniline to afford 2-[( E)-(phenylimino)methyl]phenol (2). The reduction of (2) by NaBH 4 gave 2-((phenylamino)methyl)phenol ( 3) which was reacted with chloroacetyl chloride to give 2-chloro- N-(2-hydroxybenzyl)- N-phenylacetamide ( 4). Compound ( 4) was cyclized to 4-phenyl-4,5-dihydrobenzo[ f][1,4]oxazepin-3( 2H)-one (5) by NaOH in ethanol solution. The treatment of compound (5) with P 2S 5 gave corresponding 4-phenyl-4,5-dihydrobenzo[ f][1,4]oxazepin-3( 2H)-thione (6). The structures of (5) and (6) were determined by 1H NMR and IR spectra. The optimized structural parameters and vibrational frequencies of (5) and (6) were calculated by DFT with 6-31G(d,p) basis set. The mechanism of the cyclization reaction was studied by RHF with the standard 3-21G basis set.

  19. Diaqua-bis-(1H-imidazole-4-carboxyl-ato-κ(2) N (3),O (4))manganese(II).

    PubMed

    Xiong, Zhi-Yong; Li, Lin; Zhao, Xiang-Jie; Chen, Hai-Ming

    2013-03-01

    In the title compound, [Mn(C4H3N2O2)2(H2O)2], the Mn(II) ion is located on a twofold rotation axis and displays a distorted octa-hedral coordination environment, defined by two N,O-bidentate 1H-imidazole-4-carboxyl-ate ligands in the equatorial plane and two water mol-ecules in axial positions. In the crystal, O-H⋯O and N-H⋯O hydrogen bonds link the mol-ecules into a three-dimensional supra-molecular network. π-π stacking inter-actions between the imidazole rings [centroid-centroid distances = 3.5188 (15) and 3.6687 (15) Å] further stabilize the structure. PMID:23476512

  20. Some rate 1/3 and 1/4 binary convolutional codes with an optimum distance profile

    NASA Technical Reports Server (NTRS)

    Johannesson, R.

    1977-01-01

    A tabulation of binary systematic convolutional codes with an optimum distance profile for rates 1/3 and 1/4 is given. A number of short rate 1/3 binary nonsystematic convolutional codes are listed. These latter codes are simultaneously optimal for the following distance measures: distance profile, minimum distance, and free distance; they appear attractive for use with Viterbi decoders. Comparisons with previously known codes are made.

  1. 40 CFR 721.5260 - 1,3,6-Naphthalenetrisulfonic acid, 7-[[2-[(aminocarbonyl)amino]- 4-[[4-[[2-[2-(ethenylsulfonyl...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...- - 4- ethyl]amino]- 6-fluoro-1,3,5-triazin-2-yl]amino]phenyl]azo], trisodium salt. 721.5260 Section 721...,3,6-Naphthalenetrisulfonic acid, 7- - 4- ethyl]amino]- 6-fluoro-1,3,5-triazin-2-yl]amino]phenyl]azo... substance identified as 1,3,6-Naphthalenetrisulfonic acid, 7- -4-......

  2. 40 CFR 721.5260 - 1,3,6-Naphthalenetrisulfonic acid, 7-[[2-[(aminocarbonyl)amino]- 4-[[4-[[2-[2-(ethenylsulfonyl...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...- - 4- ethyl]amino]- 6-fluoro-1,3,5-triazin-2-yl]amino]phenyl]azo], trisodium salt. 721.5260 Section 721...,3,6-Naphthalenetrisulfonic acid, 7- - 4- ethyl]amino]- 6-fluoro-1,3,5-triazin-2-yl]amino]phenyl]azo... substance identified as 1,3,6-Naphthalenetrisulfonic acid, 7- -4-......

  3. (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.

  4. (E)-2,2-Dimethyl-5-(3-phenyl-allyl-idene)-1,3-dioxane-4,6-dione.

    PubMed

    Zeng, Wu-Lan

    2010-01-01

    The title compound, C(15)H(14)O(4), was prepared by the reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione and (Z)-3-phenyl-acryl-aldehyde in ethanol. The dioxane ring is in a sofa conformation with the C atom bonded to the two methyl groups forming the flap. With the exception of the flap atom and the methyl group C atoms, all other non-H atoms are essentially planar, with an r.m.s. deviation of 0.067 (1) Å. The crystal structure is stabilized by weak inter-molecular C-H⋯O hydrogen bonds. PMID:21589113

  5. Regioselective synthesis of novel 3-allyl-2-(substituted imino)-4-phenyl-3H-thiazole and 2,2‧-(1,3-phenylene)bis(3-substituted-2-imino-4-phenyl-3H-thiazole) derivatives as antibacterial agents

    NASA Astrophysics Data System (ADS)

    Abbasi Shiran, Jafar; Yahyazadeh, Asieh; Mamaghani, Manouchehr; Rassa, Mehdi

    2013-05-01

    Several novel 3-allyl-2-(substituted imino)-4-phenyl-3H-thiazole derivatives were synthesized by the reaction of allyl-thioureas and 2-bromoacetophenone. We also report the synthesis of bis-allyl-3H thiazoles using the reaction of various isothiocyanates and 1,3-phenylenediamine. The structures of all compounds were characterized by spectral and elemental analysis. Most of the synthesized compounds exhibited efficient antibacterial activities against Salmonella enterica, Micrococcus luteus, Bacillus subtilis and Pseudomonas aeruginosa.

  6. The H3K9 methyltransferase Setdb1 regulates TLR4-mediated inflammatory responses in macrophages

    PubMed Central

    Hachiya, Rumi; Shiihashi, Takuya; Shirakawa, Ibuki; Iwasaki, Yorihiro; Matsumura, Yoshihiro; Oishi, Yumiko; Nakayama, Yukiteru; Miyamoto, Yoshihiro; Manabe, Ichiro; Ochi, Kozue; Tanaka, Miyako; Goda, Nobuhito; Sakai, Juro; Suganami, Takayoshi; Ogawa, Yoshihiro

    2016-01-01

    Proinflammatory cytokine production in macrophages involves multiple regulatory mechanisms, which are affected by environmental and intrinsic stress. In particular, accumulating evidence has suggested epigenetic control of macrophage differentiation and function mainly in vitro. SET domain, bifurcated 1 (Setdb1, also known as Eset) is a histone 3 lysine 9 (H3K9)-specific methyltransferase and is essential for early development of embryos. Here we demonstrate that Setdb1 in macrophages potently suppresses Toll-like receptor 4 (TLR4)-mediated expression of proinflammatory cytokines including interleukin-6 through its methyltransferase activity. As a molecular mechanism, Setdb1-deficiency decreases the basal H3K9 methylation levels and augments TLR4-mediated NF-κB recruitment on the proximal promoter region of interleukin-6, thereby accelerating interleukin-6 promoter activity. Moreover, macrophage-specific Setdb1-knockout mice exhibit higher serum interleukin-6 concentrations in response to lipopolysaccharide challenge and are more susceptible to endotoxin shock than wildtype mice. This study provides evidence that the H3K9 methyltransferase Setdb1 is a novel epigenetic regulator of proinflammatory cytokine expression in macrophages in vitro and in vivo. Our data will shed insight into the better understanding of how the immune system reacts to a variety of conditions. PMID:27349785

  7. The H3K9 methyltransferase Setdb1 regulates TLR4-mediated inflammatory responses in macrophages.

    PubMed

    Hachiya, Rumi; Shiihashi, Takuya; Shirakawa, Ibuki; Iwasaki, Yorihiro; Matsumura, Yoshihiro; Oishi, Yumiko; Nakayama, Yukiteru; Miyamoto, Yoshihiro; Manabe, Ichiro; Ochi, Kozue; Tanaka, Miyako; Goda, Nobuhito; Sakai, Juro; Suganami, Takayoshi; Ogawa, Yoshihiro

    2016-01-01

    Proinflammatory cytokine production in macrophages involves multiple regulatory mechanisms, which are affected by environmental and intrinsic stress. In particular, accumulating evidence has suggested epigenetic control of macrophage differentiation and function mainly in vitro. SET domain, bifurcated 1 (Setdb1, also known as Eset) is a histone 3 lysine 9 (H3K9)-specific methyltransferase and is essential for early development of embryos. Here we demonstrate that Setdb1 in macrophages potently suppresses Toll-like receptor 4 (TLR4)-mediated expression of proinflammatory cytokines including interleukin-6 through its methyltransferase activity. As a molecular mechanism, Setdb1-deficiency decreases the basal H3K9 methylation levels and augments TLR4-mediated NF-κB recruitment on the proximal promoter region of interleukin-6, thereby accelerating interleukin-6 promoter activity. Moreover, macrophage-specific Setdb1-knockout mice exhibit higher serum interleukin-6 concentrations in response to lipopolysaccharide challenge and are more susceptible to endotoxin shock than wildtype mice. This study provides evidence that the H3K9 methyltransferase Setdb1 is a novel epigenetic regulator of proinflammatory cytokine expression in macrophages in vitro and in vivo. Our data will shed insight into the better understanding of how the immune system reacts to a variety of conditions. PMID:27349785

  8. A New 1,3,4-Oxadiazole-Based Hole-Transport Material for Efficient CH3 NH3 PbBr3 Perovskite Solar Cells.

    PubMed

    Carli, Stefano; Baena, Juan Pablo Correa; Marianetti, Giulia; Marchetti, Nicola; Lessi, Marco; Abate, Antonio; Caramori, Stefano; Grätzel, Michael; Bellina, Fabio; Bignozzi, Carlo Alberto; Hagfeldt, Anders

    2016-04-01

    A new hole-transport material (HTM) based on the 1,3,4-oxadiazole moiety (H1) was prepared through a single-step synthetic pathway starting from commercially available products. Thanks to a deep HOMO level, H1 was used as HTM in CH3 NH3 PbBr3 perovskite solar cells yielding an efficiency of 5.8 %. The reference HTM (Spiro-OMeTAD), under the same testing conditions, furnished a lower efficiency of 5.1 %. Steady-state and time-resolved photoluminescence of the thin films showed good charge-extraction dynamics for H1 devices. In addition, H1 shows a large thermal stability and completely amorphous behavior (as evaluated by thermal gravimetric analysis and differential scanning calorimetry). PMID:26880477

  9. Preparation and properties of 3-amino-5-nitro-1,2,4-triazole

    SciTech Connect

    Lee, Kien-Yin; Storm, C.B.

    1990-10-01

    A novel method for the preparation of 3-amino-5-nitro-1,2,4-triazole (ANTA) has been invented. The yield of ANTA by selective reduction of the ammonium salt of 3,5-dinitro-1,2,4-triazole with hydrazine hydrate is 94% to 96% under mild reaction conditions. There is no volatile hydrazine present at the end of the reaction as it is isolated as hydrazine hydrochloride. ANTA, a potential insensitive explosive, has a crystal density of 1.82 g/cm{sup 3}, and a positive heat of formation ({Delta}H{sub f}) of 21.0 kcal/mol, and is thermally stable. The detonation velocity of ANTA, calculated at crystal density, is higher than that of triaminotrinitrobenzene. In addition to the preparation of ANTA, we have also synthesized a new hydrazinium salt of ANTA. 6 refs., 2 tabs.

  10. Thermally stable compositions including 2,4,8,10-tetranitro-5H-pyrido[3',2':4,5][1,2,3]triazolo[1,2-a]benzotriazo- l-6-ium, inner salt

    DOEpatents

    Hiskey, Michael A.; Huynh, My Hang

    2010-01-26

    An explosive formulation including 2,4,8,10-tetranitro-5H-pyrido[3',2':4,5][1,2,3]triazolo[1,2-a]benzotriazo- l-6-ium, inner salt and a high temperature binder is disclosed together with a process of preparing 2,4,8,10-tetranitro-5H-pyrido[3',2':4,5][1,2,3]triazolo[1,2-a]benzotriazo- l-6-ium, inner salt.

  11. (2E)-3-(2-Bromo-phen-yl)-1-(4,4''-difluoro-5'-meth-oxy-1,1':3',1''-terphenyl-4'-yl)prop-2-en-1-one.

    PubMed

    Fun, Hoong-Kun; Chia, Tze Shyang; Samshuddin, S; Narayana, B; Sarojini, B K

    2012-05-01

    In the title compound, C(28)H(19)BrF(2)O(2), the central benzene ring makes dihedral angles of 62.51 (18), 46.23 (18) and 48.19 (18)° with the bromo-substituted benzene ring and two terminal fluoro-substituted benzene rings, respectively. In the crystal, mol-ecules are linked by C-H⋯F hydrogen bonds into infinite chains along [110]. Weak C-H⋯π and π-π inter-actions [centroid-centroid distance = 3.683 (2) Å] also occur and short inter-molecular F⋯F contacts [2.833 (4) Å] are observed. PMID:22590218

  12. 40 CFR 721.10187 - 4-Morpholinepropanamine, N-(1,3-dimethylbutylidene)-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 4-Morpholinepropanamine, N-(1,3-dimethylbutylidene)-. 721.10187 Section 721.10187 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances...

  13. Fuel compositions containing maleic derivatives of 2,5-dimercapto-1,3,4-thiadiazole

    SciTech Connect

    Karol, T.J.

    1989-11-14

    This patent describes a diesel fuel composition. It is characterized by improved wear properties. It comprises: a major portion of middle distillates boiling in the range of about 163{degrees}to 400{degrees}C. and a minor wear improving amount of a reaction product of a maleic compound and 2,5-dimercapto-1,3,4-thiadiazole.

  14. Newsletter for Asian and Middle Eastern Languages on Computer, Volume 1, Numbers 3 & 4.

    ERIC Educational Resources Information Center

    Meadow, Anthony, Ed.

    1986-01-01

    Volume 1, numbers 3 and 4, of the newsletter on the use of non-Western languages with computers contains the following articles: "Reversing the Screen under MS/PC-DOS" (Dan Brink); "Comments on Diacritics Using Wordstar, etc. and CP/M Software for Non-Western Languages" (Michael Broschat); "Carving Tibetan in Silicon: A Tibetan Font for the…

  15. Synthesis of Some Benzimidazole Derivatives Bearing 1,3,4-Oxadiazole Moiety as Anticancer Agents

    PubMed Central

    MAZZIO, ELIZABETH; GANGAPURUM, MADHAVEI; MATEEVA, NELLY; REDDA, K. K.

    2015-01-01

    In an effort to establish new benzimidazole related structural leads with improved anticancer activity, several new benzimidazole derivatives (5a–i) with 1,3,4-oxadiazole scaffold incorporated were synthesized and studied for their anticancer activity. The anticancer screening against MDA-MB-231 breast cancer cell lines showed that compound (5c) exhibited moderate cytotoxicity. PMID:26451350

  16. 1. Building C9; 3/4 view, looking SE; showing storage tanks ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Building C-9; 3/4 view, looking SE; showing storage tanks on the west side of the building and the railroad tracks in foreground. (Ryan and Harms) - Holston Army Ammunition Plant, RDX-and-Composition-B Manufacturing Line 9, Kingsport, Sullivan County, TN

  17. Skylab missions SL/1, 2, 3, 4 photographic processing control plan

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The control parameters to be used by the Photographic Technology Division for the processing of films flown on Skylab Missions SL/1, 2, 3, and 4 are defined. The sensitometric exposure and processing conditions PTD plans to use and the procedures necessary for general film certification are described.

  18. Chemistry and properties of poly(arylene ether 1,3,4-oxadiazole)s and poly(arylene ether 1,2,4-triazole)s

    NASA Technical Reports Server (NTRS)

    Connell, J. W.; Hergenrother, P. M.; Wolf, P.

    1992-01-01

    Poly(arylene ether)s containing l,3,4-oxadiazole and 1,2,4-triazole units were prepared by the aromatic nucleophilic displacement reaction of bisphenol oxadiazole and bisphenol triazole compounds with activated aromatic dihalides. The polymers exhibited glass transition temperatures (Tg) ranging from 182 to 242 C, and several polymers exhibited melting transitions (Tm) ranging from 265 to 390 C. Inherent viscosities ranged from 1.02 to 3.40 dl/g, indicating relatively high molecular weights. Thin films exhibited tensile strengths, moduli, and elongations at 23 C of 90-110 MPa, 2.7-3.6 GPa, and 4-7 percent, respectively. Titanium-to-titanium tensile shear specimens of a poly(arylene ether 1,3,4-oxadiazole) exhibited tensile shear strengths at 23 and 150 C of 22.1 and 17.9 MPa, respectively.

  19. 3,1-Benzothiazines, 1,4-Benzodioxines and 1,4-Benzoxazines as Inhibitors of Matriptase-2: Outcome of a Focused Screening Approach

    PubMed Central

    Roydeva, Polya G.; Beckmann, Anna-Madeleine; Stirnberg, Marit; Cesar, Jožko; Kikelj, Danijel; Ilaš, Janez; Gütschow, Michael

    2016-01-01

    The liver enzyme matriptase-2 is a multi-domain, transmembrane serine protease with an extracellular, C-terminal catalytic domain. Synthetic low-molecular weight inhibitors of matriptase-2 have potential as therapeutics to treat iron overload syndromes, in particular in patients with β-thalassemia. A sub-library of 64 compounds was screened for matriptase-2 inhibition and several active compounds were identified. (S)-Ethyl 2-(benzyl(3-((4-carbamidoylphenoxy)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-2-oxoacetate ((S)-12) showed an IC50 value of less than 10 µM. Structure-activity relationships were discussed and proposals to design new matriptase-2 inhibitors were made. PMID:26771619

  20. The PVM 3.4 tracing facility and XPVM 1.1

    SciTech Connect

    Kohl, J.A.; Geist, G.A.

    1996-08-01

    One problem in developing a parallel program is monitoring its behavior for debugging and performance tuning. This paper discusses an enhanced tracing facility and tool for PVM (Parallel Virtual Machine), a message passing library for parallel processing in a heterogeneous environment. PVM supports mixed collections of workstation clusters, shared-memory multiprocessors, and massively parallel processors. The upcoming release of PVM, Version 3.4, contains a new, improved tracing facility which provides flexible, efficient access to run-time program information. This new tracing system supports a buffering mechanism to reduce perturbation of user applications caused by tracing, and a more flexible trace event definition scheme based on a self-defining data format. The new scheme expedites collection of program execution histories and allows for integration of user-defined custom trace events. Tracing instrumentation is built into the PVM library and allows on-the-fly adjustments to each task`s trace event mask, for control over the level of tracing detail. The graphical console and monitor XPVM have also been updated for better access to the new tracing functionality. Several new views have been implemented to utilize the additional tracing information now possible, including user-defined events. XPVM system has also been optimized for better real-time monitoring.

  1. Synthesis and antimalarial activity of 3,3-spiroanellated 5,6-disubstituted 1,2,4-trioxanes.

    PubMed

    Maurya, Ranjani; Soni, Awakash; Anand, Devireddy; Ravi, Makthala; Raju, Kanumuri S R; Taneja, Isha; Naikade, Niraj K; Puri, S K; Wahajuddin; Kanojiya, Sanjeev; Yadav, Prem P

    2013-02-14

    Novel 3,3-spiroanellated 5-aryl, 6-arylvinyl-substituted 1,2,4-trioxanes 19-34 have been synthesized and appraised for their antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice by oral route at doses ranging from 96 mg/kg × 4 days to 24 mg/kg × 4 days. The most active compound of the series (compound 25) provided 100% protection at 24 mg/kg × 4 days, and other 1,2,4-trioxanes 22, 26, 27, and 30 also showed promising activity. In this model, β-arteether provided 100 and 20% protection at 48 mg/kg × 4 days and 24 mg/kg × 4 days, respectively, by oral route. Compound 25 displayed a similar in vitro pharmacokinetic profile to that of reference drug β-arteether. The activity results demonstrated the importance of an aryl moiety at the C-5 position on the 1,2,4-trioxane pharmacophore. PMID:24900640

  2. Synthesis of 4-(aminoalkyl) substituted 1,3-dioxanes as potent NMDA and σ receptor antagonists.

    PubMed

    Utech, Tina; Köhler, Jens; Wünsch, Bernhard

    2011-06-01

    Elongation of the distance between the oxygen heterocycle and the basic amino moiety or ring expansion of the oxygen heterocycle of the NMDA receptor antagonists dexoxadrol and etoxadrol led to compounds with promising NMDA receptor affinity. Herein the combination of both structural features, i.e. elongation of the O-heterocycle--amine distance with a 1,3-dioxane ring is envisaged. The synthesis of aminoethyl-1,3-dioxanes 13, 22, 23 and 29 was performed by transacetalization of various acetals with pentane-1,3,5-triol, activation of the remaining free OH moiety with tosyl chloride and subsequent nucleophilic substitution. The corresponding 3-aminopropyl derivatives 33-35 were prepared by substitution of the tosylates with KCN and LiAlH4 reduction. The highest NMDA receptor affinity was found for 1,3-dioxanes with a phenyl and an ethyl residue at the acetalic position (23) followed by diphenyl (22) and monophenyl derivatives (13). Generally the NMDA affinity of primary amines is higher than the NMDA affinity of secondary and tertiary amines. Altogether the primary amine 23a (Ki=24 nM) represents the most promising NMDA receptor antagonist of this series exceeding the NMDA affinity of the mono-homologues (2-aminoethyl)-1,3-dioxolanes (3,4) and (aminomethyl)-1,3-dioxanes (5,6). Whereas the primary amine 23a turned out to be selective against σ1 and σ2 receptors the benzylamine 13d was identified as potent (Ki=19 nM) and selective σ1 antagonist, which showed extraordinarily high antiallodynic activity in the capsaicin assay. PMID:21444132

  3. Human cytochrome P450 27C1 catalyzes 3,4-desaturation of retinoids.

    PubMed

    Kramlinger, Valerie M; Nagy, Leslie D; Fujiwara, Rina; Johnson, Kevin M; Phan, Thanh T N; Xiao, Yi; Enright, Jennifer M; Toomey, Matthew B; Corbo, Joseph C; Guengerich, Frederick Peter

    2016-05-01

    In humans, a considerable fraction of the retinoid pool in skin is derived from vitamin A2 (all-trans 3,4-dehydroretinal). Vitamin A2 may be locally generated by keratinocytes, which can convert vitamin A1 (all-trans retinol) into vitamin A2 in cell culture. We report that human cytochrome P450 (hP450) 27C1, a previously 'orphan' enzyme, can catalyze this reaction. Purified recombinant hP450 27C1 bound and desaturated all-trans retinol, retinal, and retinoic acid, as well as 11-cis-retinal. Although the physiological role of 3,4-dehydroretinoids in humans is unclear, we have identified hP450 27C1 as an enzyme capable of efficiently mediating their formation. PMID:27059013

  4. (2Z,3Z)-Quinoxaline-2,3(1H,4H)-dione dioxime

    PubMed Central

    Kakanejadifard, Ali; Amani, Vahid

    2008-01-01

    The asymmetric unit of the title compound, C8H8N4O2, contains one half-mol­ecule; a twofold rotation axis bisects the molecule. An intra­molecular N—H⋯O hydrogen bond results in the formation of a five-membered ring, which displays an envelope conformation. In the crystal structure, inter­molecular O—H⋯N hydrogen bonds link the mol­ecules. PMID:21203220

  5. (2Z,3Z)-Quinoxaline-2,3(1H,4H)-dione dioxime.

    PubMed

    Kakanejadifard, Ali; Amani, Vahid

    2008-01-01

    The asymmetric unit of the title compound, C(8)H(8)N(4)O(2), contains one half-mol-ecule; a twofold rotation axis bisects the molecule. An intra-molecular N-H⋯O hydrogen bond results in the formation of a five-membered ring, which displays an envelope conformation. In the crystal structure, inter-molecular O-H⋯N hydrogen bonds link the mol-ecules. PMID:21203220

  6. 1,3-Alternate Tetraamido-Azacalix[4]arenes as Selective Anion Receptors.

    PubMed

    Canard, Gabriel; Edzang, Judicaelle Andeme; Chen, Zhongrui; Chessé, Matthieu; Elhabiri, Mourad; Giorgi, Michel; Siri, Olivier

    2016-04-11

    Six tetraaza[1.1.1.1]cyclophane derivatives bearing peripheral amide groups were prepared according to two distinct synthetic strategies that depend on the connection pattern between the aryl units. NMR experiments combined with the X-ray structures of two tetraamide derivatives 4 b and 10 show that these cavitands adopt a 1,3-alternate conformation both in solution and in the solid state. Consequently, the four amide groups of the aza[1.1.1.1]-m,m,m,m-cyclophane isomer 10 can contribute to the same recognition process towards neutral water molecules or anion guests. NMR experiments, mass spectrometry analyses and single-crystal X-ray structures confirm the anion-binding ability of this receptor. Absorption spectrophotometric titrations in nonpolar solvents provided evidence for the selectivity of 10 to chloride anions in the halide series, with a corresponding association constant Ka reaching 2.5 × 10(6) m(-1). PMID:26938487

  7. Synthesis, antiviral activity and structure-activity relationship of 1-(1-aryl-4,5-dihydro-1H-imidazoline)-3-chlorosulfonylureas and products of their cyclization.

    PubMed

    Rządkowska, Marzena; Szacoń, Elżbieta; Kaczor, Agnieszka A; Rajtar, Barbara; Świątek, Łukasz; Polz-Dacewicz, Małgorzata; Matosiuk, Dariusz

    2016-10-01

    Novel 1-(1-aryl-4,5dihydro-1H-imidazoline)-3-chlorosulfonylourea derivatives 3a-3f were synthesized in the reaction of 1-aryl-4,5-dihydro-1H-imidazol-2-amines with chlorosulfonyl isocyanate. The second series of compounds 4a-4f was prepared from the respective 1-(1-aryl-4,5-dihydro-1H-imidazoline)-3-chlorsulfonylureas 3a-3f and 1,1'-carbonyldiimidazole (CDI). The selected compounds were tested for their activity against Herpes simplex virus and coxsackievirus B3 (CVB3). It was determined that three derivatives, i.e 3d, 4a and 4d are active against Herpes simplex virus (HSV-1). Compounds 3d and 4c are active against CVB3. Their favorable activity can be primarily attributed to their low lipophilicity values. Moreover, the lack of substituent in the phenyl moiety or 4-methoxy substitution can be considered as the most beneficial for the antiviral activity. PMID:26212601

  8. Anticancer activity of 5-benzylidene-2-phenylimino-1, 3-thiazolidin-4-one (BPT) analogs.

    PubMed

    Wu, S; Guo, W; Teraishi, F; Pang, J; Kaluarachchi, K; Zhang, L; Davis, J; Dong, F; Yan, B; Fang, B

    2006-11-01

    We recently identified two compounds of 5-benzylidene-2-phenylimino-1,3-thiazolidin-4-one (BPT) analog, 5-(4-methylbenzylidene)-2-phenylamino-1,3-thiazolidin-4-one (MMPT) and 5-(2,4-dihydroxybenzylidene)-2-phenylimino-1,3-thiazolidin-4-one (DBPT), that can effectively induce apoptosis in cancer cells but not in normal cells, independently of P-glycoprotein status. To further investigate the antitumor activity of BPT analogs, we obtained 18 commercially available analogs of BPT and synthesized 7 analogs in our lab, and analyzed their antitumor activity in various cancer cells, including paclitaxel- and vinorelbine-sensitive and -resistant human lung cancer cells. Two of the compounds were more potent than MMPT or DBPT in induction of apoptosis in certain cancer cell lines and remained tumor selective. Seven compounds did not induce any cytotoxic effects in any of the cell lines tested at the highest concentration tested (31 microM). The other compounds induced cytotoxic effects in some cancer cells but not in others or were less potent than MMPT and DBPT. Cell uptake studies showed that analogs that effectively induced cell killing in paclitaxel- and vinorelbine-resistant cells could be taken up easily by those cells despite their high levels of P-glycoprotein expression. These data further demonstrate that thiazolidinone analogs are not P-glycoprotein substrates and could be useful for treatment of P-glycoprotein overexpressing refractory cancers. PMID:17105441

  9. Synthesis and in vitro antimicrobial activity of 1-methyl-3-sulfonylthio-4-aminoquinolinium chlorides.

    PubMed

    Zieba, Andrzej; Wojtyczka, Robert D; Idzik, Danuta; Kepa, Małgorzata

    2013-01-01

    Synthesis and in vitro antimicrobial activity (MIC) of novel 1-methyl-3-sulfonylthio-4-aminoquinolinium chlorides 2 are described. Compounds 2 were obtained in the reaction of 1-methyl-4-aminoquinolinium 3-thiolates 1 with sulfonyl chlorides. Antimicrobial activity of compounds 2 was investigated using Gram-positive Staphylococcus aureus, Staphylococcus saprophyticus, Staphylococcus epidermidis, Micrococcus luteus, Enterococcus faecalis, Bacillus subtilis, Corynebacterium pseudodiphtericum and Gram-negative Escherichia coil, Klebsiella pneumoniae, Proteus vulgaris, Serratia marcescens, Citrobacter freundii, Pseudomonas aeruginosa strains as well as Candida albicans. The investigated compounds exhibited growth-inhibitory activity towards Gram-positive bacteria in the 4-64 microg/mL range whereas that towards Gram-negative bacteria covered the 128-1024 microg/mL range. The highest activity was shown by compound 2c, featuring a phenylsulfonylthio substituent in the 3-quinoline position and a 4-chlorophenylamine group in the position 4. All of the investigated compounds 2 showed antifungal activity in the 32-128 microg/mL range. Correlations between antimicrobial activity and chemical structure of the tested compounds were observed. PMID:23610972

  10. Spot test for 1,3,5-triamino-2,4,6-trinitrobenzene, TATB

    DOEpatents

    Harris, B.W.

    1984-11-29

    A simple, sensitive and specific spot test for 1,3,5-triamino-2,4,6-trinitrobenzene, TATB, is described. Upon the application of the composition of matter of the subject invention to samples containing in excess of 0.1 mg of this explosive, a bright orange color results. Interfering species such as TNT and Tetryl can be removed by first treating the sample with a solvent which does not dissolve the TATB, but readily dissolves these interfering explosives.

  11. Spot test for 1,3,5-triamino-2,4,6-trinitrobenzene, TATB

    DOEpatents

    Harris, Betty W.

    1986-01-01

    A simple, sensitive and specific spot test for 1,3,5-triamino-2,4,6-trinitrobenzene, TATB, is described. Upon the application of the composition of matter of the present invention to samples containing in excess of 0.1 mg of this explosive, a bright orange color results. Interfering species such as TNT and Tetryl can be removed by first treating the sample with a solvent which does not dissolve much of the TATB, but readily dissolves these explosives.

  12. Mass spectrum of the 1-butene-3-yne-2-yl radical (i-C4H3; X2A')

    NASA Astrophysics Data System (ADS)

    Guo, Ying; Gu, Xibin; Kaiser, Ralf I.

    2006-03-01

    The crossed molecular beams method has been applied to produce the 1-butene-3-yne-2-yl radical, i-C4H3(X2A') under single collision conditions via the reaction of dicarbon molecules with ethylene. We recorded time-of-flight spectra of the radical at the center-of-mass angle (28.0°) of the parent ion (m/z = 51; C4H3+) and of the fragments at m/z = 50 (C4H2+), m/z = 49 (C4H+), m/z = 48 (C4+), m/z = 39 (C3H3+), m/z = 38 (C3H2+), m/z = 37 (C3H+), and m/z = 36 (C3+). This yielded relative intensity ratios of I(m/z = 51):I(m/z = 50):I(m/z = 49):I(m/z = 48):I(m/z = 39):I(m/z = 38):I(m/z = 37):I(m/z = 36) = 0.47 +/- 0.01:0.94 +/- 0.01:1.0:0.07 +/- 0.02:0.31 +/- 0.01:0.23 +/- 0.02:0.24 +/- 0.01:0.12 +/- 0.01 at 70 eV electron impact energy. Upper limits at mass-to-charge ratios between 27 and m/z = 24 and m/z = 14-12 were derived to be 0.02 +/- 0.01. Note that the intensity of the 13C isotopic peak of the 1-butene-3-yne-2-yl radical at m/z = 52 (13C12C3H3+) is about 0.04 +/- 0.01 relative to m/z = 51. Employing linear scaling methods, the absolute electron impact ionization cross section of the 1-butene-3-yne-2-yl radical was computed to be 7.8 +/- 1.6 × 10-16 cm2. These data can be employed to monitor the 1-butene-3-yne-2-yl radical in oxygen-poor combustion flames and in the framework of prospective explorations of planetary atmospheres (Jupiter, Saturn, Uranus, Neptune, Pluto) and of their moons (Titan, Triton, Oberon) in situ via matrix interval arithmetic assisted mass spectrometry.

  13. Synthesis and properties of 1-aryl(pyrimidinyl)-piperazinylalkyl derivatives of ethyl 3-phenyl-7-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d] pyrimidine-5-carboxylate.

    PubMed

    Sladowska, H; Sieklucka-Dziuba, M; Staniak, L; Kleinrok, Z

    1994-01-01

    Synthesis of N-aryl (pyrimidinyl)piperazinylalkyl derivatives of ethyl 2,4-dioxo-1,2,3-4-tetrahydropyrido[2,3-d]pyrimidine-5-carboxylate is reported. Some of the obtained compounds are pharmacologically active. PMID:7945716

  14. Structure-based design of 3-carboxy-substituted 1,2,3,4-tetrahydroquinolines as inhibitors of myeloid cell leukemia-1 (Mcl-1).

    PubMed

    Chen, L; Wilder, P T; Drennen, B; Tran, J; Roth, B M; Chesko, K; Shapiro, P; Fletcher, S

    2016-06-28

    Mcl-1 has recently emerged as an attractive target to expand the armamentarium in the war on cancer. Using structure-based design, 3-carboxy-substituted 1,2,3,4-tetrahydroquinolines were developed as a new chemotype to inhibit the Mcl-1 oncoprotein. The most potent compound inhibited Mcl-1 with a Ki of 120 nM, as determined by a fluorescence polarization competition assay. Direct binding was confirmed by 2D (1)H-(15)N HSQC NMR spectroscopy with (15)N-Mcl-1, which indicated that interactions with R263 and T266, and occupation of the p2 pocket are likely responsible for the potent binding affinity. The short and facile synthetic chemistry to access target molecules is expected to mediate lead optimization. PMID:26751150

  15. Lithium Diffusion Pathway in Li1.3Al0.3Ti1.7(PO4)3 (LATP) Superionic Conductor.

    PubMed

    Monchak, Mykhailo; Hupfer, Thomas; Senyshyn, Anatoliy; Boysen, Hans; Chernyshov, Dmitry; Hansen, Thomas; Schell, Karl G; Bucharsky, Ethel C; Hoffmann, Michael J; Ehrenberg, Helmut

    2016-03-21

    The Al-substituted LiTi2(PO4)3 powders Li1+xAlxTi2-x(PO4)3 (LATP) were successfully prepared by a water-based sol-gel process with subsequent calcination and sintering. The crystal structure of obtained samples was characterized at different temperatures using high-resolution synchrotron-based X-ray and neutron powder diffraction. Possible lithium diffusion pathways were initially evaluated using the difference bond-valence approach. Experimental 3D lithium diffusion pathway in LATP was extracted from the negative nuclear density maps reconstructed by the maximum entropy method. Evaluation of the energy landscape determining the lithium diffusion process in NASICON-type superionic conductor is shown for the first time. PMID:26930220

  16. Elicitor and resistance-inducing activities of beta-1,4 cellodextrins in grapevine, comparison with beta-1,3 glucans and alpha-1,4 oligogalacturonides.

    PubMed

    Aziz, Aziz; Gauthier, Adrien; Bézier, Annie; Poinssot, Benoît; Joubert, Jean-Marie; Pugin, Alain; Heyraud, Alain; Baillieul, Fabienne

    2007-01-01

    Cellodextrins (CD), water-soluble derivatives of cellulose composed of beta-1,4 glucoside residues, have been shown to induce a variety of defence responses in grapevine (Vitis vinifera L.) cells. The larger oligomers of CD rapidly induced transient generation of H2O2 and elevation in free cytosolic calcium, followed by a differential expression of genes encoding key enzymes of the phenylpropanoid pathway and pathogenesis-related (PR) proteins as well as stimulation of chitinase and beta-1,3 glucanase activities. Most of these defence reactions were also induced by linear beta-1,3 glucans (betaGlu) and alpha-1,4 oligogalacturonides (OGA) of different degree of polymerization (DP), but the intensity of some reactions induced by CD was different when compared with betaGlu and OGA effects. Moreover, desensitization assays using H2O2 production showed that cells treated with CD remained fully responsive to a second application of OGA, suggesting a different mode of perception of these oligosaccharides by grape cells. None of CD, betaGlu, or OGA induced HSR gene expression nor did they induce cell death. In accordance with elicitor activity in grapevine cells, CD-incubated leaves challenged with Botrytis cinerea also resulted in a significant reduction of the disease. Data suggest that CD could operate via other distinct reaction pathways than betaGlu and OGA. They also highlight the requirement of a specific DP for each oligosaccharide to induce the defence response. PMID:17322548

  17. Metabolites of 1,2,3,4-tetrachlorobenzene in monkey urine

    SciTech Connect

    Schwartz, H.; Chu, I.; Villeneuve, D.C.; Viau, A.; Benoit, F.M.

    1985-01-01

    (/sup 14/C(U))-Labeled 1,2,3,4-tetrachlorobenzene was administered orally to squirrel monkeys. Urine was collected from these animals, pooled and analyzed for metabolites by thin-layer chromatography, high-performance liquid chromatography, and gas chromatography-mass spectroscopy. N-Acetyl-s(2,3,4,5-tetrachlorophenyl) cysteine was shown to be the major metabolite and accounted for 85% of the radioactivity found in urine. A minor metabolite was identified at 2,3,4,5-tetrachlorophenol. This study demonstrates for the first time that an N-acetyl cysteine conjugate has been isolated and identified as metabolite of a chlorinated benzene. This pattern of chlorobenzene metabolism is significantly different from the one obtained with the rat and rabbit, where tetrachlorophenols constitute the major metabolites.

  18. Novel free fatty acid receptor 1 (GPR40) agonists based on 1,3,4-thiadiazole-2-carboxamide scaffold.

    PubMed

    Krasavin, Mikhail; Lukin, Alexey; Zhurilo, Nikolay; Kovalenko, Alexey; Zahanich, Ihor; Zozulya, Sergey; Moore, Daniel; Tikhonova, Irina G

    2016-07-01

    Free fatty acid receptor 1 (FFA1), previously known as GPR40 is a G protein-coupled receptor and a new target for treatment of type 2 diabetes. Two series of FFA1 agonists utilizing a 1,3,4-thiadiazole-2-caboxamide scaffold were synthetized. Both series offered significant improvement of the potency compared to the previously described 1,3,4-thiadiazole-based FFA1 agonists and high selectivity for FFA1. Molecular docking predicts new aromatic interactions with the receptor that improve agonist potency. The most potent compounds from both series were profiled for in vitro ADME properties (plasma and metabolic stability, LogD, plasma protein binding, hERG binding and CYP inhibition). One series suffered very rapid degradation in plasma and in presence of mouse liver microsomes. However, the other series delivered a lead compound that displayed a reasonable ADME profile together with the improved FFA1 potency. PMID:27229618

  19. Phase transition and chemical order in the ferroelectric perovskite (1-x)Bi(Mg3/4W1/4)O3-xPbTiO3 solid solution system

    NASA Astrophysics Data System (ADS)

    Stringer, C. J.; Eitel, R. E.; Shrout, T. R.; Randall, C. A.; Reaney, I. M.

    2005-01-01

    Building on the ferroelectric family based on the Bi(Me+3)O3-PbTiO3 solid solutions, the complex solid solution (1-x )Bi(Mg3/4W1/4)O3-xPbTiO3 [(1-x)BMW-xPT] was investigated. This system was found to exhibit a broad morphotropic phase boundary at x ˜0.48mol% PbTiO3 with a corresponding Curie temperature of 205°C separating pseudocubic and tetragonal ferroelectric phases. Based on dielectric, x-ray diffraction (XRD), and calorimetric data, a simple dielectric phase field diagram was established. On further structural analysis with diffraction contrast transmission electron microscopy along with XRD, evidence of B-site chemical ordering was found for the (1-x )Bi(Me'Me″)O3-xPbTiO3 perovskite family.

  20. Strong electron correlation on the Fe3O4(0 0 1) surfaces

    NASA Astrophysics Data System (ADS)

    Pinto, Henry; Elliott, Simon D.; Foster, Adam; Nieminen, R. M.

    2007-03-01

    Magnetite Fe3O4 is a fascinating material that still is not well understood and presents challenges for the state-of-the-art computational methods. This transition metal oxide undergoes a first-order metal-insulator transition at TV=120 K. The ferrimagnetic properties of Fe3O4 makes it a promising material for spintronic applications. We use a plane wave density functional theory in the generalized gradient approximation adding a Hubbard-U parameter to describe properly the strongly correlated Fe--3d electrons. Based on previous results, we compute the surface structure, magnetic properties and electronic structure of several Fe3O4(0 0 1) surfaces with (√2x√2)R45^o reconstruction. The simulated scanning tunneling microscopy images of these surfaces are compared and discussed in the light of available experimental data. Finally, we analyze the possible existence of charge ordering on the Fe3O4(0 0 1) surface and the effect on the surface electronic structure with changing the value of the Hubbard-U parameter on the superficial Fe sites. H. Pinto, S. Elliott, J.Phys.: Condens. Matter 18, 10427 (2006)

  1. General, Highly Selective Synthesis of 1,3- and 1,4-Difunctionalized Building Blocks by Regiodivergent Epoxide Opening.

    PubMed

    Funken, Nico; Mühlhaus, Felix; Gansäuer, Andreas

    2016-09-19

    We describe a regiodivergent epoxide opening (REO) featuring a catalyst-controlled synthesis of enantiomerically and diastereomerically highly enriched or pure syn- and anti- 1,3- and 1,4-difunctionalized building blocks from a common epoxide precursor. The REO is attractive for natural product synthesis and as a branching reaction for diversity-oriented synthesis with epoxides. PMID:27600090

  2. A Direct, Concise, and Enantioselective Synthesis of 2-Substituted 4,4,4-Trifluorobutane-1,3-diols Based on the Organocatalytic In Situ Generation of Unstable Trifluoroacetaldehyde.

    PubMed

    Funabiki, Kazumasa; Furuno, Yudai; Yano, Yosuke; Sakaida, Yuta; Kubota, Yasuhiro; Matsui, Masaki

    2015-12-01

    A direct, concise, and enantioselective synthesis of 2-substituted 4,4,4-trifluorobutane-1,3-diols based on the organocatalytic asymmetric direct aldol reaction of an ethyl hemiacetal of trifluoroacetaldehyde with various aldehydes was examined. A catalytic amount (30 mol %) of commercially available and inexpensive l-prolinamide is quite effective as an organocatalyst for the catalytic in situ generation of gaseous and unstable trifluoroacetaldehyde from its hemiacetal, and a successive asymmetric direct aldol reaction with various aldehydes in dichloromethane at 0 °C, followed by reduction with sodium borohydride, gives 2-substituted 4,4,4-trifluorobutane-1,3-diols in moderate to good yields (31-84%) with low diastereoselectivities and good to excellent enantioselectivities (64-97% ee). PMID:26206587

  3. Synthesis, ligand-receptor modeling studies and pharmacological evaluation of novel 4-modified-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives as potent and selective human A3 adenosine receptor antagonists.

    PubMed

    Colotta, Vittoria; Catarzi, Daniela; Varano, Flavia; Lenzi, Ombretta; Filacchioni, Guido; Martini, Claudia; Trincavelli, Letizia; Ciampi, Osele; Traini, Chiara; Pugliese, Anna Maria; Pedata, Felicita; Morizzo, Erika; Moro, Stefano

    2008-06-01

    The study of some 4-substituted-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives, designed as hA(3) adenosine receptor antagonists, is reported. The new compounds bear on the four-position different acylamino, sulfonylamino, benzylureido and benzyloxy moieties, which have also been combined with a para-methoxy group on the 2-phenyl ring or with a nitro residue at the six-position. Many derivatives show high hA(3) adenosine receptor affinities and selectivities both versus hA(1) and hA(2A) receptors. The observed structure-affinity relationships of this class of antagonists have been exhaustively rationalized using the recently published ligand-based homology modeling (LBHM) approach. The selected 4-bismethanesulfonylamino-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one (13), which shows high hA(3) affinity (K(i)=5.5nM) and selectivity versus hA(1), hA(2A) (both selectivity ratios>1800) and hA(2B) (cAMP assay, IC(50)>10,000nM) receptors, was tested in an in vitro rat model of cerebral ischemia, proving to be effective in preventing the failure of synaptic activity, induced by oxygen and glucose deprivation in the hippocampus, and in delaying the occurrence of anoxic depolarization. PMID:18468446

  4. Conformational Changes in Inositol 1,3,4,5,6-Pentakisphosphate 2-Kinase upon Substrate Binding

    PubMed Central

    Baños-Sanz, José Ignacio; Sanz-Aparicio, Julia; Whitfield, Hayley; Hamilton, Chris; Brearley, Charles A.; González, Beatriz

    2012-01-01

    Inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IP5 2-K) catalyzes the synthesis of inositol 1,2,3,4,5,6-hexakisphosphate from ATP and IP5. Inositol 1,2,3,4,5,6-hexakisphosphate is implicated in crucial processes such as mRNA export, DNA editing, and phosphorus storage in plants. We previously solved the first structure of an IP5 2-K, which shed light on aspects of substrate recognition. However, failure of IP5 2-K to crystallize in the absence of inositide prompted us to study putative conformational changes upon substrate binding. We have made mutations to residues on a region of the protein that produces a clasp over the active site. A W129A mutant allowed us to capture IP5 2-K in its different conformations by crystallography. Thus, the IP5 2-K apo-form structure displays an open conformation, whereas the nucleotide-bound form shows a half-closed conformation, in contrast to the inositide-bound form obtained previously in a closed conformation. Both nucleotide and inositide binding produce large conformational changes that can be understood as two rigid domain movements, although local changes were also observed. Changes in intrinsic fluorescence upon nucleotide and inositide binding are in agreement with the crystallographic findings. Our work suggests that the clasp might be involved in enzyme kinetics, with the N-terminal lobe being essential for inositide binding and subsequent conformational changes. We also show how IP5 2-K discriminates between inositol 1,3,4,5-tetrakisphosphate and 3,4,5,6-tetrakisphosphate enantiomers and that substrate preference can be manipulated by Arg130 mutation. Altogether, these results provide a framework for rational design of specific inhibitors with potential applications as biological tools for in vivo studies, which could assist in the identification of novel roles for IP5 2-K in mammals. PMID:22745128

  5. Exploring the 3-piperidin-4-yl-1H-indole scaffold as a novel antimalarial chemotype.

    PubMed

    Santos, Sofia A; Lukens, Amanda K; Coelho, Lis; Nogueira, Fátima; Wirth, Dyann F; Mazitschek, Ralph; Moreira, Rui; Paulo, Alexandra

    2015-09-18

    A series of 3-piperidin-4-yl-1H-indoles with building block diversity was synthesized based on a hit derived from an HTS whole-cell screen against Plasmodium falciparum. Thirty-eight compounds were obtained following a three-step synthetic approach and evaluated for anti-parasitic activity. The SAR shows that 3-piperidin-4-yl-1H-indole is intolerant to most N-piperidinyl modifications. Nevertheless, we were able to identify a new compound (10d) with lead-like properties (MW = 305; cLogP = 2.42), showing antimalarial activity against drug-resistant and sensitive strains (EC50 values ∼ 3 μM), selectivity for malaria parasite and no cross-resistance with chloroquine, thus representing a potential new chemotype for further optimization towards novel and affordable antimalarial drugs. PMID:26295174

  6. A hydrogen-1, chlorine-35, and yttrium-89 NMR complex formation study of aqueous Y(ClO 4) 3 and Y(NO 3) 3 solutions

    NASA Astrophysics Data System (ADS)

    Fratiello, Anthony; Kubo-Anderson, Vicki; Bolinger, Todd; Cordero, Cristina; Demerit, Barbara; Flores, Thomas; Matejka, Dennis; Perrigan, Richard

    A Y (III) coordination study of Y (ClO 4) 3 and Y (NO 3) 3 solutions in aqueous solvent mixtures has been carried out by hydrogen-1, chlorine-35, and yttrium-89 NMR spectroscopy. An accurate measurement of the Y(III) hydration number by a direct hydrogen-1 NMR method was not possible in Y (ClO 4) 3 solutions, even at -115°C, but these experiments were successful for Y(NO 3) 3 solutions. The hydrogen-1 spectra for the Y(NO 3) 3 solutions revealed two coordinated water signals, appearing at different temperatures, and corresponding to total Y(III) hydration numbers of 2.5 to 3.5. The yttrium-89 NMR spectra showed one signal for Y(ClO 4) 3 solutions for all conditions of concentration and temperature, whereas the Y (NO 3) 3 solution spectra at low temperature consisted of two signals, which varied in intensity with solvent composition. The hydrogen-1 and yttrium-89 NMR results were interpreted in terms of combinations of (H 2O) 4Y (NO 3) 2+ and (H 2O) 2Y ( NO3) {1}/{2}+ in the Y(NO 3) 3 solutions, but similar experiments, along with chlorine-35 NMR data, ruled out inner-shell complex formation in the Y(ClO 4) 3 systems.

  7. Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Antinociceptive Agents.

    PubMed

    Altıntop, Mehlika Dilek; Can, Özgür Devrim; Demir Özkay, Ümide; Kaplancıklı, Zafer Asım

    2016-01-01

    In the current work, new 1,3,4-thiadiazole derivatives were synthesized and investigated for their antinociceptive effects on nociceptive pathways of nervous system. The effects of these compounds against mechanical, thermal and chemical stimuli were evaluated by tail-clip, hot-plate and acetic acid-induced writhing tests, respectively. In addition, activity cage was performed to assess the locomotor activity of animals. The obtained data indicated that compounds 3b, 3c, 3d, 3e, 3g and 3h increased the reaction times of mice both in the hot-plate and tail-clip tests, indicating the centrally mediated antinociceptive activity of these compounds. Additionally, the number of writhing behavior was significantly decreased by the administration of compounds 3a, 3c, 3e and 3f, which pointed out the peripherally mediated antinociceptive activity induced by these four compounds. According to the activity cage tests, compounds 3a, 3c and 3f significantly decreased both horizontal and vertical locomotor activity of mice. Antinociceptive behavior of these three compounds may be non-specific and caused by possible sedative effect or motor impairments. PMID:27490523

  8. Child Proportional Scaling: Is 1/3 = 2/6 = 3/9 = 4/12?

    ERIC Educational Resources Information Center

    Boyer, Ty W.; Levine, Susan C.

    2012-01-01

    The current experiments examined the role of scale factor in children's proportional reasoning. Experiment 1 used a choice task and Experiment 2 used a production task to examine the abilities of kindergartners through fourth-graders to match equivalent, visually depicted proportional relations. The findings of both experiments show that accuracy…

  9. One-pot sonochemical synthesis of 1,3-thiazolidin-4-ones using nano-CdZr4(PO4)6 as a robust heterogeneous catalyst.

    PubMed

    Safaei-Ghomi, Javad; Navvab, Maryam; Shahbazi-Alavi, Hossein

    2016-07-01

    An efficient three-component synthesis of 1,3-thiazolidin-4-ones is described by one-pot condensation of aldehydes, aniline and thioglycolic acid with nano-CdZr4(PO4)6 as a robust heterogeneous catalyst under ultrasonic irradiation. Use of simple and readily available starting materials, experimental simplicity, applying the sonochemical methodology as an efficient method and innocuous means of activation in synthetic chemistry are some advantages of this protocol. PMID:26964928

  10. Pharmacophore modeling, 3D-QSAR, and docking study of pyrozolo[1,5-a]pyridine/4,4-dimethylpyrazolone analogues as PDE4 selective inhibitors.

    PubMed

    Tripuraneni, Naga Srinivas; Azam, Mohammed Afzal

    2015-11-01

    Phosphodiesterases 4 enzyme is an attractive target for the design of anti-inflammatory and bronchodilator agents. In the present study pharmacophore and atom based 3D-QSAR studies were carried out for pyrozolo[1,5-a]pyridine/4,4-dimethylpyrazolone analogues. A five point pharmacophore model was developed using 52 molecules having pIC50 values ranging from 9.959 to 3.939. The best predictive pharmacophoric hypothesis AHHRR.3 was characterized by survival score (2.944), cross validated (r(2) = 0.8147), regression coefficient (R(2) = 0.9545) and Fisher ratio (F =173) with 4 component PLS factor. Results explained that one hydrogen bond acceptor, two aromatic rings and two hydrophobic groups are crucial for the PDE4 inhibition. The docking studies of all selected inhibitors in the active site of PDE4 showed crucial hydrogen bond interactions with Asp392, Asn395 Tyr233, and Gln443 residues. The pharmacophoric features R15 and R16 exhibited π-π stacking with His234, Phe414, and Phe446 residues. The generated model was further validated by carrying out the decoy test. The binding free energies of these inhibitors in the catalytic domain of 1XMU were calculated by the molecular mechanics/generalized Born surface area VSGB 2.0 method. The results of molecular dynamics simulation confirmed the extra precision docking-predicted priority for binding sites, the accuracy of docking, and the reliability of active conformations. Pyrozolo[1,5-a]pyridine/4,4-dimethylpyrazolone analogues in this study showed lower binding affinity toward PDE3A in comparison to PDE4. Outcomes of the present study provide insight in designing novel molecules with better PDE4 inhibitory activity. Graphical Abstract Pyrozolo[1,5-a]pyridines/4,4-dimethylpyrazolones. PMID:26499496

  11. Aspirin Breaks the Crosstalk between 3T3-L1 Adipocytes and 4T1 Breast Cancer Cells by Regulating Cytokine Production.

    PubMed

    Hsieh, Chia-Chien; Huang, Yu-Shan

    2016-01-01

    Breast cancer is one of the most common cancers in women worldwide. The obesity process is normally accompanied by chronic, low-grade inflammation. Infiltration by inflammatory cytokines and immune cells provides a favorable microenvironment for tumor growth, migration, and metastasis. Epidemiological evidence has shown that aspirin is an effective agent against several types of cancer. The aim of this study is to investigate the anti-inflammatory and anti-cancer effects of aspirin on 3T3-L1 adipocytes, 4T1 murine breast cancer cells, and their crosstalk. The results showed that aspirin treatment inhibited differentiation and lipid accumulation by 3T3-L1 preadipocytes, and decreased the secretion of the inflammatory adipokine MCP-1 after stimulation with tumor necrosis factor (TNF)-α or conditioned medium from RAW264.7 cells. In 4T1 cells, treatment with aspirin decreased cell viability and migration, possibly by suppressing MCP-1 and VEGF secretion. Subsequently, culture of 4T1 cells in 3T3-L1 adipocyte-conditioned medium (Ad-CM) and co-culture of 3T3-L1 and 4T1 cells using a transwell plate were performed to clarify the relationship between these two cell lines. Aspirin exerted its inhibitory effects in the transwell co-culture system, as well as the conditioned-medium model. Aspirin treatment significantly inhibited the proliferation of 4T1 cells, and decreased the production of MCP-1 and PAI-1 in both the Ad-CM model and co-culture system. Aspirin inhibited inflammatory MCP-1 adipokine production by 3T3-L1 adipocytes and the cell growth and migration of 4T1 cells. It also broke the crosstalk between these two cell lines, possibly contributing to its chemopreventive properties in breast cancer. This is the first report that aspirin's chemopreventive activity supports the potential application in auxiliary therapy against obesity-related breast cancer development. PMID:26794215

  12. Discovery of (R)-1-(3-(4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)-2-(dimethylamino)ethanone (CHMFL-FLT3-122) as a Potent and Orally Available FLT3 Kinase Inhibitor for FLT3-ITD Positive Acute Myeloid Leukemia.

    PubMed

    Li, Xixiang; Wang, Aoli; Yu, Kailin; Qi, Ziping; Chen, Cheng; Wang, Wenchao; Hu, Chen; Wu, Hong; Wu, Jiaxin; Zhao, Zheng; Liu, Juan; Zou, Fengming; Wang, Li; Wang, Beilei; Wang, Wei; Zhang, Shanchun; Liu, Jing; Liu, Qingsong

    2015-12-24

    FLT3-ITD mutant has been observed in about 30% of AML patients and extensively studied as a drug discovery target. On the basis of the structure of PCI-32765 (ibrutinib), a BTK kinase inhibitor that was recently reported to bear FLT3 kinase activity through a structure-guided drug design approach, we have discovered compound 18 (CHMFL-FLT3-122), which displayed an IC50 of 40 nM against FLT3 kinase and achieved selectivity over BTK kinase (over 10-fold). It significantly inhibited the proliferation of FLT3-ITD positive AML cancer cell lines MV4-11 (GI50 = 22 nM), MOLM13/14 (GI50 = 21 nM/42 nM). More importantly, 18 demonstrated 170-fold selectivity between FLT3 kinase and c-KIT kinase (GI50 = 11 nM versus 1900 nM) in the TEL-fusion isogenic BaF3 cells indicating a potential to avoid the FLT3/c-KIT dual inhibition induced myelosuppression toxicity. In the cellular context it strongly affected FLT3-ITD mediated signaling pathways and induced apoptosis by arresting the cell cycle into the G0/G1 phase. In the in vivo studies 18 demonstrated a good bioavailability (30%) and significantly suppressed the tumor growth in MV4-11 cell inoculated xenograft model (50 mg/kg) without exhibiting obvious toxicity. Compound 18 might be a potential drug candidate for FLT3-ITD positive AML. PMID:26630553

  13. Quenching rate constants for reactions of Ar(4p'[1/2]0, 4p[1/2]0, 4p[3/2]2, and 4p[5/2]2) atoms with 22 reagent gases

    NASA Astrophysics Data System (ADS)

    Sadeghi, N.; Setser, D. W.; Francis, A.; Czarnetzki, U.; Döbele, H. F.

    2001-08-01

    The total quenching rate constants of argon atoms in the 4p'[1/2]0, 4p[1/2]0, 4p[3/2]2, and 4p[5/2]2 states (2p1, 2p5, 2p6, and 2p8, respectively, in the Paschen numbering system) by rare gases, H2, D2, N2, CO, NO, O2, F2, Cl2, CO2, NO2, CH4, C2H2, C2H4, C2H6, CF4, CHF3, and SF6 have been determined at room temperature. These four excited states of argon (energy 13.09-13.48 eV) were selectively prepared by two-photon excitation from the ground state using VUV (184-190 nm range) laser pulses. The total quenching rates were deduced from the pressure dependence of the decay times of the excited-state atoms, measured by observing their fluorescence emission intensities in the presence of added reagents. The quenching constants increase from values of ≅0.01×10-10 cm3 atom-1 s-1 for Ne, to ≅0.1×10-10 cm3 atom-1 s-1 for He and Ar, and to very large values, (5-15)×10-10 cm3 atom-1 s-1, for most polyatomic molecules, F2, Cl2, and O2. The quenching mechanisms of the Ar(4p,4p') atoms are briefly discussed and compared to the reactions of the Ar(4s,4s') metastable and resonance state atoms, 11.55-11.83 eV, which can serve as a reference.

  14. Evidence of Polymorphism on the Antitrypanosomal Naphthoquinone (4E)-2-(1H-Pyrazol-3-ylamino)-4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one

    PubMed Central

    Sperandeo, Norma R.; Faudone, Sonia N.

    2013-01-01

    The aim of this study was to characterize the solid state properties of (4E)-2-(1H-pyrazol-3-ylamino)-4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one (BiPNQ), a compound with a significant inhibitory activity against Trypanosoma cruzi, the etiological agent of Chagas disease (American trypanosomiasis). Methods used included Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Fourier Transform Infrared Spectroscopy (FTIR), Powder X-Ray Diffraction (PXRD), Hot Stage, and Confocal Microscopy. Two BiPNQ samples were obtained by crystallization from absolute methanol and 2-propanol-water that exhibited different thermal behaviours, PXRD patterns, and FTIR spectra, indicating the existence of an anhydrous form (BiPNQ-I) and a solvate (BIPNQ-s), which on heating desolvated leading to the anhydrous modification BiPNQ-I. It was determined that FTIR, DSC, and PXRD are useful techniques for the characterization and identification of the crystalline modifications of BiPNQ. PMID:24106678

  15. Merlin's tumor suppression linked to inhibition of the E3 ubiquitin ligase CRL4DCAF1

    PubMed Central

    Li, Wei

    2010-01-01

    The mechanism by which the FERM domain protein Merlin, encoded by the tumor suppressor NF2, restrains cell proliferation is poorly understood. Prior studies have suggested that Merlin exerts its antimitogenic effect by interacting with multiple signaling proteins located at or near the plasma membrane. We have recently observed that Merlin translocates into the nucleus and binds to and inhibits the E3 ubiquitin ligase CRL4DCAF1. Genetic evidence indicates that inactivation of Merlin induces oncogenic gene expression, hyperproliferation, and tumorigenicity by unleashing the activity of CRL4DCAF1. In addition to providing a potential explanation for the diverse effects that loss of Merlin exerts in multiple cell types, these findings suggest that compounds inhibiting CRL4DCAF1 may display therapeutic efficacy in Neurofibromatosis type 2 and other cancers driven by Merlin inactivation. PMID:21084862

  16. 4-(4-Chloro­phen­yl)-1-[3-(4-fluoro­benzo­yl)prop­yl]-4-hydroxy­piperidin-1-ium 2,4,6-trinitro­phenolate (haloperidol picrate)

    PubMed Central

    Jasinski, Jerry P.; Butcher, Ray J.; Hakim Al-Arique, Q. N. M.; Yathirajan, H. S.; Narayana, B.

    2009-01-01

    In the title salt, C21H24ClFNO2 +·C6H2N3O7 −, the dihedral angle between the aromatic rings in the cation is 16.5 (1)°. The piperidium ring adopts a slightly distorted chair conformation. Strong hydrogen-bonding inter­actions occur between the N—H and O—H functions of the 4-hydroxy­piperidin-1-ium ring and the phenolate and p-NO2 O atoms of the picrate anion. In addition, a variety of weak C—H⋯O and π–π ring inter­actions between cations and cation–anion neighbors [centroid–centroid distances = 3.597 (1) and 3.848 (10) Å] further consolidate the packing. PMID:21577866

  17. Synthesis and structure of 1-methyl-2,3-dihydro-1,2,4-triazolium salts and their free bases

    SciTech Connect

    Pinson, V.V.; Krustalev, V.A.; Matveeva, Z.M.; Zelenin, K.N.

    1985-04-01

    1-Methyl-2,3-dihydro-1,2,4-triazolium iodides can be obtained by reacting methylhydrazones with S-methylthioamide hydriodides, by condensing 2-methylamidrazone hydriodides with aldehydes and ketones, or by reacting methyl iodide with 1-alkylidene(or arylidene) benzamidrazones. In solutions these salts are capable of undergoing tautomerism to 1-alkylidene(or arylidene)-2-methylamidrazone hydriodides. The influence of the structural factors on the position of the tautomeric equilibrium has been studied. The free bases obtained by neutralization of the respective salts by an alkali metal hydroxide are heretofore undescribed 1-alkylidene(or arylidene)-2-methylhydrazidoimines or 4-triazolines, depending on their structure. Under the action of oxygen, these compounds are readily oxidized to substituted 1-methyl-1,2,4-triazoles with heating.

  18. α(1,3)-Fucosyltransferases FUT4 and FUT7 Control Murine Susceptibility to Thrombosis

    PubMed Central

    Wang, Huili; Morales-Levy, Maria; Rose, Jason; Mackey, Lantz C.; Bodary, Peter; Eitzman, Daniel; Homeister, Jonathon W.

    2014-01-01

    The α(1,3)-fucosyltransferases, types IV and VII (FUT4 and FUT7, respectively), are required for the synthesis of functional selectin-type leukocyte adhesion molecule ligands. The selectins and their ligands modulate leukocyte trafficking, and P-selectin and its ligand, P-selectin glycoprotein ligand-1, can modulate hemostasis and thrombosis. Regulation of thrombosis by FUT4 and/or FUT7 activity was examined in mouse models of carotid artery thrombosis and collagen/epinephrine-induced thromboembolism. Mice lacking both FUT4 and FUT7 (Fut−/− mice) had a shorter time to occlusive thrombus formation in the injured carotid artery and a higher mortality due to collagen/epinephrine-induced pulmonary thromboemboli. Mice lacking P-selectin or P-selectin glycoprotein ligand-1 did not have a prothrombotic phenotype. Whole blood platelet aggregation was enhanced, and plasma fibrinogen content, clot weight, and clot strength were increased in Fut−/− mice, and in vitro clot lysis was reduced compared with wild type. Fut4−/−, but not Fut7−/−, mice had increased pulmonary thromboembolism-induced mortality and decreased thromboemboli dissolution in vivo. These data show that FUT4 and FUT7 activity regulates thrombosis in a P-selectin– and P-selectin glycoprotein ligand-1–independent manner and suggest that FUT4 activity is important for thrombolysis. PMID:23562273

  19. Synthesis and Antimicrobial Screening of Novel Thioglycosides and Acyclonucleoside Analogs Carrying 1,2,3-Triazole and 1,3,4-Oxadiazole Moieties.

    PubMed

    Aouad, M R

    2016-01-01

    The solvent-free 1,3-dipolar cycloaddition reaction of dimethylacetylene dicarboxylate (1) with 2-chlorophenyl azide (2) afforded 1,2,3-triazole diester 3 that upon hydrazinolysis, furnished the corresponding bis-acid hydrazide 4. The treatment of compound 4 with carbon disulfide in a refluxing potassium hydroxide solution furnished the desired bis-1,3,4-oxadiazole-2-thione 5 tethered to a 1,2,3-triazole moiety. The respective SOx-glycosides 9-11 were obtained by glycosylation of bis-oxadiazole 5 with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide (6), 2,3,4,6-tetra-O-acetyl-α-d-galactopyranosyl bromide (7), and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl chloride (8) in dry acetone in the presence of Et3N, which acted as a base. However, alkylation of 5 with halogeno-alkanol 12 or 13, chloroglycerol 14, bromoethers 20 or 21, and epichlohydrin 22 in the presence of K2CO3 in DMF yielded the corresponding acyclonucleoside analogs 16-18 and 23-25. The isopropylidenes 19 and acetyl derivatives 26-28 of the products were also prepared. The newly synthesized compounds were characterized by (1)H NMR, (13)C NMR, 2D NMR, and mass spectra. The compounds were screened for their antibacterial and antifungal activities. A number of the tested compounds exhibited significant antimicrobial activity compared to the reference drugs. PMID:26810028

  20. Crystal structure of (Z)-4-[1-(4-acetyl-anilino)ethyl-idene]-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one.

    PubMed

    Mahfouz, Refaat M; Demircioğlu, Zeynep; Abbady, Mohamed S; Büyükgüngör, Orhan

    2015-01-01

    In the solid state, the title compound, C20H19N3O2, adopts the keto-amine tautomeric form, with the H atom attached to the N atom, which participates in an intra-molecular N-H⋯O hydrogen bond with an S(6) ring motif. The dihedral angles between the pyrazole ring and the phenyl and benzene rings are 3.69 (10) and 46.47 (9)°, respectively. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, generating C(16) chains propagating in [301]. Weak aromatic π-π stacking inter-actions [centroid-centroid distances = 3.6123 (10) and 3.6665 (10) Å] link the chains into a three-dimensional network. PMID:25705461