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Sample records for 1 3 4

  1. Rapid, Microwave Accelerated Synthesis of [1,2,4]Triazolo[3,4-b][1,3,4]oxadiazoles from 4-Acylamino-1,2,4-Triazoles.

    PubMed

    Breunig, Stesphanie L; Olson, Margaret E; Harki, Daniel A

    2016-09-07

    1,2,4-Triazoles and 1,3,4-oxadiazoles are prevalent moieties in pharmaceutical agents, yet fused [1,2,4]-triazolo[3,4-b][1,3,4]oxadiazoles are surprisingly under-represented for both synthesis and biological application. We report a rapid, two-step synthesis of [1,2,4]-triazolo[3,4-b][1,3,4]oxadiazoles from commercial 4-amino-1,2,4-triazoles that is highlighted by a microwave accelerated intramolecular cyclization to generate the fused ring system. Our efforts to optimize reaction conditions and elucidate reaction mechanism are also described.

  2. 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.

  3. 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).

  4. 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.

  5. A novel dilithiation approach to 3,4-dihydro-2H-1,3-benzothiazines, 3,4-Dihydro-2H-1,3-benzoxazines, and 2,3,4,5-tetrahydro-1,3-benzothiazepines.

    PubMed

    Katritzky, Alan R; Xu, Yong-Jiang; Jain, Ritu

    2002-11-15

    3,4-Dihydro-2H-1,3-benzothiazines 4, 3,4-dihydro-2H-1,3-benzoxazines 9, and 2,3,4,5-tetrahydro-1,3-benzothiazepines 6 were synthesized by directed ortho-lithiation of thiophenols and phenols and by side-chain lithiation of substituted thiophenols, respectively, in one-pot by reacting with N,N-bis[(benzotriazol-1-yl)methyl]amines 3 as 1,3-biselectrophile synthons.

  6. (3R,4S)-3,4-Isopropylidenedioxy-5-phenylsulfonylmethyl-3,4-dihydro-2H-pyrrole 1-oxide

    PubMed Central

    Flores, Mari Fe; Garcia, P.; M. Garrido, Narciso; Sanz, Francisca; Diez, David

    2011-01-01

    The title compound, C14H17NO5S, was prepared by oxidation of (2R,3S,4R)-2-phenyl­sulfonyl­methyl-1-hy­droxy-3,4-iso­pro­pyl­idene­dioxy­pyrrolidine. Its crystal structure confirms unequivocally its configuration. Two inter­molecular C—H⋯O inter­actions help to establish the packing. PMID:21754431

  7. Intramolecular Diels–Alder/1,3-Dipolar Cycloaddition Cascade of 1,3,4-Oxadiazoles

    PubMed Central

    Elliott, Gregory I.; Fuchs, James R.; Blagg, Brian S. J.; Ishikawa, Hayato; Tao, Houchao; Yuan, Z.-Q.; Boger, Dale L.

    2008-01-01

    Full details of a systematic exploration of the intramolecular [4+2]/[3+2] cycloaddition cascade of 1,3,4-oxadiazoles are disclosed in which the scope and utility of the reaction are defined. PMID:16895427

  8. 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...

  9. 1,2,3,3',4',6'-Hexaacetyl-4,6-O-benzyl-idenesucrose.

    PubMed

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

    2011-01-26

    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.

  10. Synthesis and pharmacological properties of benzothiazole, 1,3-4-oxadiazole and 1,3,4-thiadiazole derivatives.

    PubMed

    Santagati, M; Modica, M; Santagati, A; Russo, F; Caruso, A; Cutuli, V; Di Pietro, E; Amico-Roxas, M

    1994-12-01

    The reaction of the 2-amino-substituted 1,3,4-oxadiazoles 9, 10 and the benzothiazoles 11, 12 with ethyl cyanoacetate is described. The obtained cyanoacetamide derivatives 13-16 gave the benzylidene derivatives 18-21 by condensation with benzaldehyde. 2-Phenyl-5-amino-1,3,4-oxadiazolo[3,2-a]pyrimidin-7-one (17) was also obtained. Moreover, the preparation of 6,7,8,9-tetraydro-5H-1,3,4-thiadiazolo[2,3-b]quinazolin++ +-5-thio-derivatives 22-25 and N-(1,3,4-thiadiazol-2-yl-5-substituted)-3,4-5,6-tetrahydro-anthran ilic acids 26-29 is also described. All above compounds and compounds, related to them, 1-8 were tested for their analgesic and antiinflammatory activities and the pharmacological screening results are reported and discussed.

  11. Synthesis of Novel 2,5-Disubstituted-1,3,4-thiadiazoles Clubbed 1,2,4-Triazole, 1,3,4-Thiadiazole, 1,3,4-Oxadiazole and/or Schiff Base as Potential Antimicrobial and Antiproliferative Agents.

    PubMed

    Rezki, Nadjet; Al-Yahyawi, Amjad M; Bardaweel, Sanaa K; Al-Blewi, Fawzia F; Aouad, Mohamed R

    2015-09-02

    In the present study, a new series of 2,5-disubstituted-1,3,4-thiadiazole tethered 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazole and Schiff base derivatives were synthesized and characterized by IR, ¹H-NMR, (13)C-NMR, MS and elemental analyses. All compounds were screened for their antibacterial, antifungal and antiproliferative activity. Some of the synthesized derivatives have displayed promising biological activity.

  12. 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.

  13. 1-Methyl-4H-3,1-benzoxazine-2,4(1H)dione

    PubMed Central

    Deifel, Nicholas P.; Cherney, Emily; Hunt, David A.; Chan, Benny C.

    2010-01-01

    In its crystal structure, the title compound, C9H7NO3, forms π-stacked dimers, with a centroid–centroid distance of 3.475 (5) Å between the benzenoid and the 2,4 dicarbonyl oxazine rings. These dimers then form staircase-like linear chains through further π-stacking between the benzenoid rings [centroid–centroid distance of 3.761 (2) Å]. The methyl-H atoms are disordered due to rotation about the C—N bond and were modeled with equal occupancy. PMID:21580413

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. PAX3-FOXO1 and FGFR4 in alveolar rhabdomyosarcoma.

    PubMed

    Marshall, Amy D; van der Ent, Martijn A; Grosveld, Gerard C

    2012-10-01

    We and others have identified FGFR4 as a direct transcriptional target of the alveolar rhabdomyosarcoma (ARMS) specific fusion protein, PAX3-FOXO1. We hypothesized fibroblast growth factor receptor 4 (FGFR4) may act as an effector of PAX3-FOXO1, contributing to PAX3-FOXO1 tumorigenic phenotypes. However, we demonstrate that enhanced expression of FGFR4 does not contribute to inhibited differentiation, enhanced proliferation, or transformation downstream of PAX3-FOXO1 in primary mouse myoblasts. Therefore we were unable to identify any contribution of up regulation of wild type FGFR4 to PAX3-FOXO1 driven tumorigenesis. Conversely, a constitutively active mutant of FGFR4 can enhance primary myoblast proliferation and transformation, indicating activating mutations of FGFR4 could contribute to the development and progression of ARMS. We sequenced the FGFR4 mRNA from five ARMS cell lines and identified no somatic mutations, nor any association with any human single nucleotide polymorphism within the FGFR4 coding region.

  20. 1-Benzyl-4-(naphthalen-1-yl)-1H-1,2,3-triazole

    PubMed Central

    Sarmiento-Sánchez, Juan I.; Aguirre, Gerardo; Rivero, Ignacio A.

    2011-01-01

    In the title compound, C19H15N3, the benzyl group is almost perpendicular to the triazole ring [dihedral angle = 80.64 (8)°], while the napthyl group makes an angle of 30.27 (12)° with the plane of the triazole ring. This conformation is different from the 1-benzyl-4-phenyl-1H-1,2,3-triazole analogue, which has the benzyl ring system at an angle of 87.94° and the phenyl group at an angle of 3.35° to the plane of the triazole ring. PMID:21837221

  1. Poly(1,3,4-oxadiazoles) via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Wolf, Peter (Inventor)

    1992-01-01

    Poly(1,3,4-oxadiazoles) (POX) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl) 1,3,4-oxadiazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The polymerizations are carried out in polar aprotic solvents such as sulfolane or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl) 1,3,4-oxadiazole monomers are synthesized by reacting 4-hydroxybenzoic hydrazide with phenyl 4-hydrobenzoate in the melt and also by reacting aromatic dihydrazides with two moles of phenyl 4-hydroxybenzoate in the melt. This synthetic route has provided high molecular weight POX of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the large variety of activated aromatic dihalides which are available.

  2. 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

  3. 1. 3/4 VIEW, LOOKING NE. Philadelphia & Reading Railroad, ...

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

    1. 3/4 VIEW, LOOKING NE. - Philadelphia & Reading Railroad, Pedestrian Suspension Bridge, Foot of Sixth Street at Schuylkill River (formerly spanned Philadelphia & Reading main line at Reading Depot), Reading, Berks County, PA

  4. 1,3,4-oxadiazole: a biologically active scaffold.

    PubMed

    Khalilullah, H; Ahsan, M J; Hedaitullah, Md; Khan, S; Ahmed, B

    2012-07-01

    There has been considerable interest in the development of novel compounds with anticonvulsant, antidepressant, analgesic, anti-inflammatory, antiallergic, antipsychotic, antimicrobial, antimycobecterial, antitumour, antiviral and antitubercular activities. 1,3,4-oxadiazoles constitute an important class of compounds for new drug development. Therefore, many researchers have synthesized these compounds as target structures and evaluated their biological activities. These observations led to the development of new 1,3,4-oxadiazole derivatives. This review article describes the various biological activities associated with 1,3,4-oxadiazole ring system and is useful in guiding the researchers across the world working on this moiety and consequently have been instrumental in the advancement of 1,3,4-oxadiazole chemistry.

  5. 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).

  6. 3-Methyl-1,2,4-triazolo[3,4-a]phthalazine monohydrate.

    PubMed

    Dutkiewicz, Grzegorz; Chidan Kumar, C S; Yathirajan, H S; Mayekar, A N; Kubicki, Maciej

    2009-10-10

    In the crystal structure of the title compound, C(10)H(8)N(4)·H(2)O, the organic mol-ecules are approximately planar [maximum deviation from the least-squares plane = 0.041 (2) Å]. Two mol-ecules are connected by two water mol-ecules via O-H⋯N hydrogen bonding into dimers, which are located around centres of inversion. In the crystal, mol-ecules are stacked in the a-axis direction, with mean distances between the π systems of 3.43 (1) and 3.46 (1) Å [centroid-centroid distances are 3.604 (2) and 3.591 (2) Å].

  7. Cometabolism of 3,4-dichlorobenzoate by Acinetobacter sp. strain 4-CB1.

    PubMed Central

    Adriaens, P; Focht, D D

    1991-01-01

    When Acinetobacter sp. strain 4-CB1 was grown on 4-chlorobenzoate (4-CB), it cometabolized 3,4-dichlorobenzoate (3,4-DCB) to 3-chloro-4-hydroxybenzoate (3-C-4-OHB), which could be used as a growth substrate. No cometabolism of 3,4-DCB was observed when Acinetobacter sp. strain 4-CB1 was grown on benzoate. 4-Carboxyl-1,2-benzoquinone was formed as an intermediate from 3,4-DCB and 3-C-4-OHB in aerobic and anaerobic resting-cell incubations and was the major transient intermediate found when cells were grown on 3-C-4-OHB. The first dechlorination step of 3,4-DCB was catalyzed by the 4-CB dehalogenase, while a soluble dehalogenase was responsible for dechlorination of 3-C-4-OHB. Both enzymes were inducible by the respective chlorinated substrates, as indicated by oxygen uptake experiments. The dehalogenase activity on 3-C-4-OHB, observed in crude cell extracts, was 109 and 44 nmol of 3-C-4-OHB min-1 mg of protein-1 under anaerobic and aerobic conditions, respectively. 3-Chloro-4-hydroxybenzoate served as a pseudosubstrate for the 4-hydroxybenzoate monooxygenase by effecting oxygen and NADH consumption without being hydroxylated. Contrary to 4-CB metabolism, the results suggest that 3-C-4-OHB was not metabolized via the protocatechuate pathway. Despite the ability of resting cells grown on 4-CB or 3-C-4-OHB to carry out all of the necessary steps for dehalogenation and catabolism of 3,4-DCB, it appeared that 3,4-DCB was unable to induce the necessary 4-CB dehalogenase for the initial p-dehalogenation step.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2036004

  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. Direct Aminolysis of Ethoxycarbonylmethyl 1,4-Dihydropyridine-3-carboxylates.

    PubMed

    Vigante, Brigita; Rucins, Martins; Plotniece, Aiva; Pajuste, Karlis; Luntena, Iveta; Cekavicus, Brigita; Bisenieks, Egils; Smits, Rufus; Duburs, Gunars; Sobolev, Arkadij

    2015-11-12

    The ethoxycarbonylmethyl esters of 1,4-dihydropyridines were directly converted into carbamoylmethyl esters in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) in good to excellent yields under mild conditions. The use of TBD is crucial for the successful aminolysis of ethoxycarbonylmethyl ester of 1,4-dihydropyridines with secondary amines as without it the reaction does not proceed at all. The aminolysis reaction proceeded regioselectively, as the alkyl ester conjugated with the 1,4-dihydropyridine cycle was not involved in the reaction. Screening of other N-containing bases, such as triethylamine (TEA), pyridine, 4-(N,N-dimethylamino)pyridine (DMAP), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), imidazole, tetramethyl guanidine (TMG) and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) as catalysts revealed no activity in the studied reaction.

  10. 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.

  11. 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.

  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...

  13. 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 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...

  14. 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...

  15. 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...

  16. 3,4-trans-4-Aryl-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolates--new group of potential cardiotonic drugs.

    PubMed

    Krauze, A; Vītoliņa, R; Garaliene, V; Sīle, L; Klusa, V; Duburs, G

    2005-11-01

    3,4-trans-4-Aryl-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolates 6-11 were prepared by a Michael reaction of N-acetonylpyridinium chloride with 3-aryl-2-cyanothioacrylamides or by a one-pot three-carbon condensation of N-acetonylpyridinium chloride, aromatic aldehyde and 2-cyanothioacetamide, and their cardiotonic properties were studied. 3,4-trans-5-cyano-2-hydroxy-2-methyl-4-(3-nitrophenyl)-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolate 8 was considered as a lead compound in this series since it in vitro experiments (spontaneously beating rat atria) showed a cardiotonic activity similar to that of milrinone 2, however compound 8 induced activity at lover concentrations and without influence on chronotropic action of the heart. Unlike milrinone 2, thiolate 8 in vivo experiments (anaesthetized rats) did not influence blood pressure and heart rate. The acute toxicity of compound 8 was more than 10 times lower than that of milrinone 2.

  17. 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…

  18. 1,3,4-oxadiazole derivatives as potential biological agents.

    PubMed

    Sun, Juan; Makawana, Jigar A; Zhu, Hai-Liang

    2013-10-01

    The synthesis of novel compound libraries along with screening is a rapid and effective approach for the discovery of potential chemical agents, and it becomes an important method in pharmaceutical chemistry research. 1,3,4- oxadiazole derivatives as the typical heterocyclic compounds, exhibit a broad spectrum of biological activities and vital leading compounds for the development of chemical drugs. Herein, we focus on the synthesis and screening of novel 1,3,4-oxadiazoles derivatives with antimicrobial, antitumor or antiviral activities during the past decade. In this review, we discussed the synthetic development of 1,3,4-oxadiazoles derivatives, and also the relevant bioactivity and their prospects as the potential chemical drugs.

  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. Electron impact mass spectral fragmentation of 3a,5-disubstituted 1, 3-diphenyl-3a,4,5,6-tetra-hydro-3H-1,2,4-triazolo[4,3-a][1, 5]benzo-diazepines.

    PubMed

    Xu, J; Zhang, Q; Wang, C

    2000-01-01

    The mass spectrometric behaviour of six 3a,5-disubstituted 1, 3-diphenyl-3a,4,5,6-tetrahydro-3H-1,2,4-triazolo[4,3-a][1, 5]benzodiazepines has been studied with the aid of mass-analyzed ion kinetic energy spectrometry and accurate mass measurements under electron impact ionization. All compounds show a tendency to eliminate (substituted) styrene molecules, aryl radicals, arylmethyl radicals or phenylnitrene (PhN:). All of the resulting fragment ions, except [M - PhN:](+.), could further undergo a reverse [2 + 3] cycloaddition. The [M - PhN:](+.) ions could further lose styrene derivatives and undergo a ring enlargement rearrangement. The molecular ions also show a tendency to eliminate a phenyl radical, and the [M - Ph](+) ions could eliminate styrene derivatives. The [M - R(1)CH = CH(2)](+.) ions could further lose NH(2) to yield stable tetracyclic 1,3-diphenyl-1,2,4-triazolo[4,3-d]phenanthridine ions, which could further lose benzonitrile, or undergo a reverse [2 + 3] cycloaddition. The molecular ions could also undergo a reverse [2 + 3] cycloaddition to produce N-phenylbenzonitrile imine ions and 2, 4-disubstituted 2,3-dihydro-1H-1,5-benzodiazepine ions, whose further fragmentations were also investigated.

  1. Polymerization of 1,3-Dienes with Functional Groups. 4.

    NASA Astrophysics Data System (ADS)

    Takenaka, Katsuhiko; Shibata, Natsuyo; Tsuchida, Shinsuke; Takeshita, Hiroki; Miya, Masamitsu; Shiomi, Tomoo

    Anionic polymerization of N,N-diethyl-2-methylene-3-butenamide (DEA), which is a 1,3-butadiene derivative containing a diethylamide function, was carried out in tetrahydrofurane (THF) under various conditions. When DEA was polymerized in THF at -78°C using potassium naphthalenide (K-Naph) or diphenylmethylpotassium (DPMK) as an initiator, a polymer of predictable molecular weight with a narrow molecular weight distribution was obtained. However, the rate of polymerization was extremely slow to reach 80% conversion after 720 h. When the polymerization temperature was raised to 20°C, a low molecular weight oligomer with a broad molecular weight distribution was obtained because of a chain transfer reaction. On the other hand, no such side reaction occurred even at 20°C, when polymerization was carried out in the presence of LiCl. Also, the chain transfer reaction did not occur in lithium naphthalenide (Li-Naph) initiated polymerization. The microstructure of the polymer prepared using a potassium counter cation was a 1 : 1 mixture of 1,4-E and 1,2- structures. In the case of Li-Naph or DPMK/LiCl systems, the microstructure was a complicated mixture of 1,4-E, 1,4-Z, and 1,2-structures.

  2. Action of an endo-β-1,3(4)-glucanase on cellobiosyl unit structure in barley β-1,3:1,4-glucan

    PubMed Central

    Kuge, Takao; Nagoya, Hiroki; Tryfona, Theodora; Kurokawa, Tsunemi; Yoshimi, Yoshihisa; Dohmae, Naoshi; Tsubaki, Kazufumi; Dupree, Paul; Tsumuraya, Yoichi; Kotake, Toshihisa

    2015-01-01

    β-1,3:1,4-Glucan is a major cell wall component accumulating in endosperm and young tissues in grasses. The mixed linkage glucan is a linear polysaccharide mainly consisting of cellotriosyl and cellotetraosyl units linked through single β-1,3-glucosidic linkages, but it also contains minor structures such as cellobiosyl units. In this study, we examined the action of an endo-β-1,3(4)-glucanase from Trichoderma sp. on a minor structure in barley β-1,3:1,4-glucan. To find the minor structure on which the endo-β-1,3(4)-glucanase acts, we prepared oligosaccharides from barley β-1,3:1,4-glucan by endo-β-1,4-glucanase digestion followed by purification by gel permeation and paper chromatography. The endo-β-1,3(4)-glucanase appeared to hydrolyze an oligosaccharide with degree of polymerization 5, designated C5-b. Based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight (ToF)/ToF-mass spectrometry (MS)/MS analysis, C5-b was identified as β-Glc-1,3-β-Glc-1,4-β-Glc-1,3-β-Glc-1,4-Glc including a cellobiosyl unit. The results indicate that a type of endo-β-1,3(4)-glucanase acts on the cellobiosyl units of barley β-1,3:1,4-glucan in an endo-manner. PMID:26027730

  3. 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.

  4. 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

    2015-03-26

    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.

  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. 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...

  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. Enantiomeric separation of racemic 4-aryl-1,4-dihydropyridines and 4-aryl-1,2,3,4-tetrahydropyrimidines on a chiral tetraproline stationary phase.

    PubMed

    Dai, Zhi; Pittman, Charles U; Li, Tingyu

    2013-04-01

    The chromatographic chiral resolution of 4-aryl-1,4-dihydropyridines (1-32), 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines (33-38), and 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines (39-41) was studied on a tetraproline-immobilized chiral column synthesized in our lab. This tetraproline chiral stationary phase can resolve most of these compounds. The 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines (33-38) and 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines (39-41) were more efficiently resolved than the racemic 4-aryl-1,4-dihydropyridines on the tetraproline chiralstationary phase. Analytes with 5,5-dimethyl groups (39-41) were less efficiently resolved than analytes without 5,5-dimethyl substituents (1-16). The 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines (39-41) without a sulfur atom were much more efficiently resolved than 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines (33-38). No obvious electronic effects on the resolution of any of these analytes (1-41) were observed on the tetraproline chiral stationary phase. The tetraproline chiral stationary phase separated enantiomers mainly via hydrogen bonding interactions.

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

    SciTech Connect

    Lai, Peng-Yeh; Tsai, Chong-Bin; 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. Spectral Analysis and Crystal Structures of 4-(4-Methylphenyl)-6-Phenyl-2,3,3a, 4-Tetrahydro-1H-Pyrido[3,2,1-jk]Carbazole and 4-(4-Methoxyphenyl)-6-Phenyl-2,3,3a, 4-Tetrahydro-1H-Pyrido[3,2,1-jk]Carbazole.

    PubMed

    Kalyana Sundar, J; Natarajan, S; Chitra, S; Paul, Nidhin; Manisankar, P; Muthusubramanian, S; Suresh, J

    2011-01-01

    The crystal structures of 4-(4-methylphenyl)-6-phenyl-2,3,3a,4-tetrahydro-1H-pyrido[3,2,1-jk]carbazole (IIa) and 4-(4-methoxyphenyl)-6-phenyl-2,3,3a,4-tetrahydro-1H-pyrido[3,2,1-jk]carbazole (IIb) were elucidated by single crystal X-ray diffraction. Compound (IIa), C28H25N, crystallizes in the triclinic system, space group P-1, with a = 8.936(2) Å, b = 10.490(1) Å, c = 11.801(1) Å, α = 102.69(5) (°) ,  β = 103.27(3) (°) , γ = 93.80(1) (°) , and Z = 2. The compound (IIb), C28H25NO, crystallizes in the monoclinic system, space group P21/a, with a = 11.376(5) Å, b = 14.139(3) Å, c = 13.237(4) Å, β = 97.41(3) (°) , and Z = 4. In both the structures, the pyrido ring adopts a twist boat conformation and the carbazole molecule has the twisted envelope structure with C3 and C13 at the flap. No classical hydrogen bonds are observed in the crystal structures. Details of the preparation, structures, and spectroscopic properties of the new compounds are discussed.

  11. Mutagenicity in Salmonella and sister chromatid exchange in mice for 1,4-, and 1,3-, 2,4-, and 3,4-dimethylphenanthrenes

    SciTech Connect

    Sinsheimer, J.E.; Giri, A.K.; Hooberman, B.H.; Jung, K.Y.; Gopalaswamy, R.; Koreeda, M. )

    1991-01-01

    The mutagenicity in Salmonella and in vivo sister chromatid exchange in the bone-marrow cells of mice was determined for 1,4-, 1,3-, 2,4-, and 3,4-dimethylphenanthrene (DMPh) with the objective to study the relative importance of substitution at the 1 and 4 positions of this series of methylated phenanthrenes. For both tests, 1,4-DMPh was decidedly more genotoxic than the remaining regioisomers. While the well recognized role of steric crowding in the bay region is a factor in this enhanced genotoxicity, equally important is substitution at the 1 position with its potential to inhibit detoxication through 9,10-diol formation.

  12. Quinolone antimicrobial agents. 1. Versatile new synthesis of 1-alkyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids.

    PubMed

    Mitscher, L A; Gracey, H E; Clark, G W; Suzuki, T

    1978-05-01

    A flexible reaction sequence has been developed which starts with readily available anthranilic acids or isatoic anhydrides and leads regiospecifically to 1-alkyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids after reaction with 1,3-dicarbonyl compounds. The sequence is superior to earlier published methods by allowing electron-releasing and -withdrawing groups in any position on the aro;atic ring, by allowing convenient substitution at C2, and better overall yield. A number of new and known antimicrobial agents were prepared and tested in vitro, demonstrating, inter alia, that substitution of the H at C2 abolished antibacterial activity.

  13. Mass spectrometric study of 1,2,4- and 1,3,4-oxadiazoles containing indole substituents

    SciTech Connect

    Ushakova, R.L.; Mikaya, A.I.; Zaikin, V.G.; Kelarev, V.I.; Shveikhgeimer, G.A.

    1986-10-01

    1,2,4- and 1,3,4-Oxadiazoles containing indole substituents decompose upon electron impact due to breakage of bonds in the oxadiazole ring. Skeletal rearrangements may occur in the molecular ions of 2,5-diaryl-1,3,4-oxadiazoles due to migration of the aryl groups.

  14. 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.

  15. 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.

  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. Vibrational Spectra of 3-(Adamantan-1-YL)-4-(2-Propen-1-YL)-1 H-1,2,4-Triazole-5(4 H)-Thione

    NASA Astrophysics Data System (ADS)

    Gladkov, L. L.; Matsukovich, A. S.; Pavich, T. A.; Gaponenko, S. V.; El-Emam, A. A.

    2017-01-01

    Vibrational spectra of 3-(adamantan-1-yl)-4-(2-propen-1-yl)-1H-1,2,4-triazole-5(4H)-thione (C15H21N3S), which was promising for drug development, were studied experimentally and theoretically. The geometric structure and normal modes of the molecule and its dimer were calculated using quantum-mechanical density functional theory. It was shown that the experimentally obtained vibrational spectra were due to dimeric C15H21N3S structures. This conclusion was confirmed by spectra of the isotopically substituted compound with a deuterated imine. Bands at 1496 and 1549 cm-1 were identified as markers of dimer formation. Bands at 936 and 1244 cm-1 were found to be markers of intermolecular interactions of adamantane fragments.

  18. 5-(Adamantan-1-yl)-3-[(4-benzyl­piperazin-1-yl)meth­yl]-1,3,4-oxadiazole-2(3H)-thione

    PubMed Central

    El-Emam, Ali A.; El-Brollosy, Nasser R.; Attia, Mohamed I.; Said-Abdelbaky, Mohammed; García-Granda, Santiago

    2012-01-01

    The mol­ecule of the title compound, C24H32N4OS, is a functionalized 1,3,4-oxadiazole-2-thione with substituted piperazine and adamantanyl substituents attached at the 3- and 5-positions, respectively, of the oxadiazole spacer with an approximately C-shaped conformation. In the crystal, mol­ecules form dimers via C—H⋯S inter­action. The piperazine ring has a chair conformation; the substituents S, methyl­ene C and adamantane C of the essentially planar oxadiazole ring are approximately in the same plane, with distances of −0.046 (2), −0.085 (5) and 0.003 (4) Å, respectively. The dihedral angle between the planes of the phenyl and oxadiazole rings is 31.3 (3)°. PMID:22798843

  19. Synthesis and Characterization of 1,4-Dihydro-3,1-Benzoxazines and 1,2,3,4-Tetrahydroquinazolines: An Unknown Structure Determination Experiment

    ERIC Educational Resources Information Center

    Bendorf, Holly D.; Vebrosky, Emily N.; Eck, Brian J.

    2016-01-01

    In this experiment for an upper-division course in organic structure determination, each student prepares an unknown compound and characterizes the product using multiple spectroscopic techniques. The unknowns, 2-aryl-substituted 1,4-dihydro-3,1-benzoxazines and 1,2,3,4-tetrahydroquinazolines, are prepared in a single step by the condensation of…

  20. (+/-)-4-Aryl-4,5-dihydro-3H-1,3-benzodiazepines. 2. Nuclear-substituted analogues of (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine and (+/-)-4,5-dihydro-2-ethyl-3-methyl-4-phenyl-3H-1,3-benzodiazepine as potential antidepressant agents.

    PubMed

    Martin, L L; Setescak, L L; Worm, M; Crichlow, C A; Geyer, H M; Wilker, J C

    1982-04-01

    Antidepressant-like activity, as evidenced by marked inhibition of tetrabenazine-induced ptosis, was previously reported for (+/-)-4,5-dihydro-4-phenyl-3H-1,3-benzodiazepine derivatives. Since optimal antitetrabenazine activity was associated with (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine (9k, HRP 543) and the 2-ethyl-3-methyl analogue (10k), the synthesis and evaluation of nuclear-substituted derivatives of these two compounds was also investigated. The initial synthesis involved Friedel-Crafts acylation of substituted benzenes with 2-nitrophenylacetyl chloride to afford 1-aryl-2-(2-nitrophenyl)ethanones 2, which were converted in five steps to (+/-)-alpha-aryl-N-methyl-2-nitrobenzeneethanamines 7. Greater flexibility with respect to the introduction of nuclear substituents was achieved by conversion of 2-nitrotoluene derivatives to 2 via acylation of intermediate beta-(dimethylamino)-2-nitrostyrenes with various aroyl chlorides and hydrolysis. Reductive amination of 2 with methylamine and sodium cyanoborohydride afforded 7 directly and significantly reduced the number of synthetic steps. Reduction of 7a-j to diamines 8a-j and cyclization with appropriate ortho esters gave nuclear-substituted analogues of 9k and 10k. Marked antitetrabenazine activity was associated with many of these compounds. Significant enhancement of activity with respect to the unsubstituted analogues 9k and 10k was not observed, with the exception of 9c which appeared to be slightly more potent than 9k.

  1. 3,4-Dihydroxy-1,6-bis(4-methoxyphenyl)hexa-2,4-diene-1,6-dione, its 4-methylphenyl analogue, and a potassium salt of 2-hydroxy-4-(4-methoxyphenyl)-4-oxobut-2-enoic acid.

    PubMed

    Nye, Luke; Turnbull, Mark M; Wikaira, Jan L

    2013-11-01

    Reaction of 4-methoxyacetophenone with diethyl oxalate under basic conditions produced 3,4-dihydroxy-1,6-bis(4-methoxyphenyl)hexa-2,4-diene-1,6-dione, C20H18O6, (1). The molecules lie across a crystallographic inversion centre and intramolecular hydrogen bonding, similar to acetylacetone, is observed, confirming that the molecule is in the di-enol-dione tautomeric form. Additional O-H...O hydrogen bonds link the molecules into chains parallel to the b axis. The structure is compared with that of redetermined 4-methylphenyl compound 3,4-dihydroxy-1,6-bis(4-methylphenyl)hexa-2,4-diene-1,6-dione, C20H18O4, (2), which crystallizes in a similar fashion. The salt, catena-poly[[μ2-2-hydroxy-4-(4-methoxyphenyl)-4-oxobut-2-enoato-κ(3)O(1),O(2):O(4)][μ2-2-hydroxy-4-(4-methoxyphenyl)-4-oxobut-2-enoic acid-κ(2)O(1):O(4)]potassium], [K(C11H9O5)(C11H10O5)]n, (3), was isolated as a by-product of the synthesis of (1). The two organic species are linked by a strong hydrogen bond between the carboxylic acid and carboxylate groups. They are further stabilized and linked into a double-chain structure via the seven-coordinate potassium ion.

  2. 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.

  3. Bis(5-amino-3-carb­oxy-1H-1,2,4-triazol-4-ium) dihydrogenphosphate nitrate 5-amino-1H-1,2,4-triazol-4-ium-3-carboxyl­ate

    PubMed Central

    Berrah, Fadila; Bouchene, Rafika; Bouacida, Sofiane; Daran, Jean-Claude

    2012-01-01

    In the title compound, 2C3H5N4O2 +·H2PO4 −·NO3 −·C3H4N4O2, three independent 5-amino-1H-1,2,4-triazol-3-carb­oxy­lic acid moieties are observed. Two are in the form of cations, while the third is in the zwitterionic form. The triazole rings in the two cations are almost coplanar, making an angle of 4.11 (7)°. Layers parallel to the (20-1) plane, resulting from hydrogen bonding of the organic mol­ecules and the nitrate anions, are linked via H2PO4 − infinite zigzag chains running parallel to the c axis. The crystal studied was an inversion twin, with refined components of 0.33 (7) and 0.67 (7). PMID:22590233

  4. Phosphine-catalyzed [4+1] annulation of 1,3-(aza)dienes with maleimides: highly efficient construction of azaspiro[4.4]nonenes.

    PubMed

    Yang, Mei; Wang, Tianyi; Cao, Shixuan; He, Zhengjie

    2014-11-14

    Phosphine-catalyzed [4+1] annulation of electron-deficient 1,3-dienes or 1,3-azadienes with maleimides has been successfully developed under very mild conditions, providing a convenient and highly efficient method for constructing 2-azaspiro[4.4]nonenes and 1,7-diazaspiro[4.4]nonenes. This reaction represents the first example of [4+1] cyclization between electron-deficient 4π-conjugated systems and non-allylic phosphorus ylides.

  5. Inositol 1,3,4,5-tetrakisphosphate negatively regulates chemoattractant-elicited PtdIns(3,4,5)P3 signaling in neutrophils

    PubMed Central

    Jia, Yonghui; Subramanian, Kulandayan K.; Erneux, Christophe; Pouillon, Valerie; Hattori, Hidenori; Jo, Hakryul; You, Jian; Zhu, Daocheng; Schurmans, Stephane; Luo, Hongbo R.

    2007-01-01

    Summary Many neutrophil functions are mediated by PtdIns(3,4,5)P3, an essential cellular signaling molecule that exerts its function by mediating protein translocation via binding to their pleckstrin homolog (PH)-domains. In mammalian cells, its activity was previously thought to be dependent solely upon concentrations of PtdIns(3,4,5)P3 in the plasma membrane. Here we show that inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), a cytosolic small molecule, binds the same PH domain and compete for its binding to PtdIns(3,4,5)P3. In neutrophils, chemoattractant stimulation triggers rapid elevation in Ins(1,3,4,5)P4 level. Depletion of Ins(1,3,4,5)P4 by deleting InsP3KB, which converts Ins(1,4,5)P3 to Ins(1,3,4,5)P4, enhances the membrane translocation of PtdIns(3,4,5)P3 specific PH domain, thus augments the PtdIns(3,4,5)P3 downstream signals, leading to enhanced sensitivity to chemoattractant stimulation, elevated superoxide production, and enhanced neutrophil recruitment to inflamed peritoneal cavity. On the contrary, augmentation of intracellular Ins(1,3,4,5)P4 level blocks chemoattractant-elicited PH domain membrane translocation and dramatically decreases the sensitivity of neutrophils to chemoattractant stimulation. These findings establish a novel role for Ins(1,3,4,5)P4 in cellular signal transduction pathways and provide an alternative mechanism for modulating PtdIns(3,4,5)P3 signaling in neutrophils, namely relative levels of Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3. PMID:17825589

  6. (S)-Methyl 2-[(3R,4R)-2-benzyl-3-(2-fur-yl)-1-oxo-1,2,3,4-tetra-hydro-isoquinoline-4-carboxamido]-3-(1H-indol-3-yl)propanoate.

    PubMed

    Baktır, Zeliha; Akkurt, Mehmet; Kandinska, Meglena I; Bogdanov, Milen G; Büyükgüngör, Orhan

    2009-06-06

    The title compound, C(33)H(29)N(3)O(5), was synthesized by the reaction of racemic trans-2-benzyl-3-(2-fur-yl)-1-oxo-1,2,3,4-tetra-hydro-isoquinoline-4-carboxylic acid, l-tryptophan methyl ester and diisopropylcarbodiimide in dry dichloro-methane. The furan ring is disordered over two positions in a 0.859 (14):0.141 (14) ratio. In the 1,2,3,4-tetra-hydro-iso-quin-oline ring system, the heterocyclic ring is not planar, with puckering parameters Q(T) = 0.448 (2) Å, θ = 64.9 (3) and ϕ = 268.3 (3)°. The crystal is extended into a three-dimensional supra-molecular architecture through inter-molecular N-H⋯O hydrogen bonds and C-H⋯π inter-actions. The absolute structure was assigned by reference to the chiral starting material.

  7. Synthesis and antimicrobial activity of styryl/pyrrolyl/pyrazolyl sulfonylmethyl-1,3,4-oxadiazolyl amines and styryl/pyrrolyl/pyrazolyl sulfonylmethyl-1,3,4-thiadiazolyl amines.

    PubMed

    Sravya, G; Yamini, G; Padmavathi, V; Padmaja, A

    2016-10-21

    A new class of mono and bis heterocycles - styryl sulfonylmethyl-1,3,4-oxadiazolyl/1,3,4-thiadiazolyl amines, pyrrolyl sulfonylmethyl-1,3,4-oxadiazolyl/1,3,4-thiadiazolyl amines and pyrazolyl sulfonylmethyl-1,3,4-oxadiazolyl/1,3,4-thiadiazolyl amines were prepared from the synthetic intermediate Z-styrylsulfonylacetic acid adopting simple and well versed synthetic methodologies and studied their antimicrobial activity. Amongst all the tested compounds styryl thiadiazole 5c exhibited promising antimicrobial activity against Pseudomonas aeruginosa and Penicillium chrysogenum.

  8. The genes encoding the Eph-related receptor tyrosine kinase ligands LERK-1 (EPLG1, Epl1), LERK-3 (EPLG3, Epl3), and LERK-4 (EPLG4, Epl4) are clustered on human chromosome 1 and mouse chromosome 3

    SciTech Connect

    Cerretti, D.P.; Lyman, S.D.; Kozlosky, C.J.

    1996-04-15

    Hek and elk are members of the eph-related family of receptor tyrosine kinases. Recently, we isolated five cDNAs encoding membrane-bound ligands to hek and elk. Because of the promiscuous nature of their binding, we have termed these proteins ligands of the eph-related kinases or LERKs. The LERKs can be divided into two subgroups by virtue of their sequence identity, binding properties, and mode of cell membrane attachment. For example, LERK-2 (EPLG2, Epl2) and LERK-5 (EPLG5, Epl5) are type 1 transmembrane proteins, while LERK-1 (EPLG4, Epl4) are anchored to the membrane by glycosyl-phosphatidylinositol (GPI) linkage. Using Southern hybridization analysis of human x rodent somatic cell hybrid DNAs, we have assigned the genes that encode the GPI-anchored LERKs (EPLG1, EPLG3, and EPLG4) to human chromosome 1. Fluorescence in situ hybridization to metaphase chromosome preparations using genomic clones from each locus refined this localization to chromosome 1, bands q21-q22. In addition, Southern blot analysis of DNA from interspecific backcross mice indicated that the mouse homologues Epl1, Epl3, and Epl4 map to a homologous region on mouse chromosome 3. 36 refs., 2 figs.

  9. 5,6-Dihydro-2H-1,3-dithiolo[4,5-b][1,4]dioxine-2-thione

    PubMed Central

    Wang, Guan-nan; Xiao, Xun-wen; Cai, Tongjiang; Huang, Qin

    2011-01-01

    The title mol­ecule, C5H4O2S3, consists of a planar [mean deviation = 0.020 (1) Å] 1,3-dithiole-2-thione unit with an ethyl­enedi­oxy group in the 4,5-positions. The dioxine ring is in a twist-chair conformation. PMID:21754789

  10. 5,6-Dihydro-2H-1,3-dithiolo[4,5-b][1,4]dioxine-2-thione.

    PubMed

    Wang, Guan-Nan; Xiao, Xun-Wen; Cai, Tongjiang; Huang, Qin

    2011-06-01

    The title mol-ecule, C(5)H(4)O(2)S(3), consists of a planar [mean deviation = 0.020 (1) Å] 1,3-dithiole-2-thione unit with an ethyl-enedi-oxy group in the 4,5-positions. The dioxine ring is in a twist-chair conformation.

  11. 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.

  12. 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.

  13. 1/4-BPS M-theory bubbles with SO(3) × SO(4) symmetry

    NASA Astrophysics Data System (ADS)

    Kim, Hyojoong; Kiu Kim, Kyung; Kim, Nakwoo

    2007-08-01

    In this paper we generalize the work of Lin, Lunin and Maldacena on the classification of 1/2-BPS M-theory solutions to a specific class of 1/4-BPS configurations. We are interested in the solutions of 11 dimensional supergravity with SO(3) × SO(4) symmetry, and it is shown that such solutions are constructed over a one-parameter familiy of 4 dimensional almost Calabi-Yau spaces. Through analytic continuations we can obtain M-theory solutions having AdS2 × S3 or AdS3 × S2 factors. It is shown that our result is equivalent to the AdS solutions which have been recently reported as the near-horizon geometry of M2 or M5-branes wrapped on 2 or 4-cycles in Calabi-Yau threefolds. We also discuss the hierarchy of M-theory bubbles with different number of supersymmetries.

  14. Cytotoxicity and bioactivation mechanism of benzyl 2-chloro-1,1,2-trifluoroethyl sulfide and benzyl 1,2,3,4,4-pentachlorobuta-1,3-dienyl sulfide

    SciTech Connect

    Veltman, J.C.; Dekant, W.; Guengerich, F.P.; Anders, M.W.

    1988-01-01

    The metabolism and cytotoxicity of benzyl 1,2,3,4,4-pentachlorobuta-1,3-dienyl sulfide (1) and benzyl 2-chloro-1,1,2-trifluoroethyl sulfide (2) were studied as an alternative test of the hypothesis that the toxicity of the cysteine S-conjugates S-(pentachlorobutadienyl)-L-cysteine and S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine is associated with their metabolism to unstable thiols; the expectation was that the benzyl sulfides 1 and 2 would undergo cytochrome P-450 dependent benzylic hydroxylation and that the intermediate hemimercaptals would eliminate unstable, cytotoxic thiols. This expectation was realized: 1 and 2 were cytotoxic in isolated rat hepatocytes. The cytotoxicity of 1 was greater in hepatocytes from phenobarbital-treated rats compared with control rats and in male then in female rats and was inhibited by carbon monoxide and 2-(N,N-diethylamino)ethyl 2,2-diphenylvalerate HCl (SKF 525-A). Benzyl sulfides 1 and 2 were metabolized to benzaldehyde by rat hepatic microsomal fractions and by a purified, reconstituted cytochrome P-450/sub PB-B/ system. Benzaldehyde was not cytotoxic. These results provide support for the hypothesis that benzyl sulfides 1 and 2 and the corresponding cysteine S-conjugates yield unstable thiols, which may give rise to acylating agents or to stable, but toxic, terminal products that are responsible for the cytotoxic effects of benzyl sulfides and cysteine S-conjugates.

  15. Synthesis and characterization of tritium labeled N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide.

    PubMed

    Hong, Yang; Hynes, John; Tian, Yuan; Balasubramanian, Balu; Bonacorsi, Samuel

    2015-08-01

    N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide is a potent C-C chemokine receptor 1 (CCR1) antagonist. The compound, possessing benzamide functionality, successfully underwent tritium/hydrogen (T/H) exchange with an organoiridium catalyst (Crabtree's catalyst). The labeling pattern in the product was studied with liquid chromatography-mass spectrometry, time-of-flight mass spectrometry, and (3) H-NMR. Overall, multiple labeled species were identified. In addition to the anticipated incorporation of tritium in the benzamide moiety, tritium labeling was observed in the valine portion of the molecule including substitution at its chiral carbon. Using authentic standards, liquid chromatography analysis of the labeled compound showed complete retention of stereochemical configuration.

  16. 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

  17. 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

    2007-07-03

    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.

  18. 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- pyrimidinyl]azo-.kappaN1] -4-hydroxy-.kappa.O)-5-nitrobenzenesulfonato(3-)]-, trisodium. (a)...

  19. 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- pyrimidinyl]azo-.kappaN1] -4-hydroxy-.kappa.O)-5-nitrobenzenesulfonato(3-)]-, trisodium. (a)...

  20. 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.

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-1 Site identification... available, and will be supplemented in some instances by surface investigations and conceptual...

  2. The incommensurate magnetic structure of Er3Cu4Ge4below 1 K

    NASA Astrophysics Data System (ADS)

    Cadogan, J. M.; Ryan, D. H.; Cranswick, L. M. D.

    2010-01-01

    The magnetic structure of Er3Cu4Ge4 was previously studied down to 1.5 K by Wawrzyńska et al. who found that the Er(2d) sublattice orders at 8 K in a commensurate, doubled structure (kd = [0 1/2 0]) with an Er moment close to the free-ion value of 9 μB. By contrast, the Er(4e) sublattice ordered at 3.5 K in an incommensurate structure (ke = [0 0.883(2) 0]) with a greatly reduced moment (about one-third of the free-ion value). We have extended this study by high-resolution neutron powder diffraction down to 0.34 K in an effort to establish if the Er(4e) sublattice eventually locks-in and attains its free-ion moment (in keeping with our 166Er Mössbauer work). We observed a change in the Er(4e) order, beginning at 1.4 K, leading to a magnetic structure at 0.34 K which has almost locked-in but with (ke = [0.1 2/3 0]) and a still-reduced Er moment.

  3. Mineralization of diuron [3-(3,4-dichlorophenyl)-1, 1-dimethylurea] by co-immobilized Arthrobacter sp. and Delftia acidovorans.

    PubMed

    Bazot, S; Bois, P; Joyeux, C; Lebeau, T

    2007-05-01

    Mineralization of diuron has not been previously demonstrated despite the availability of some bacteria to degrade diuron into 3,4-dichloroaniline (3,4-DCA) and others that can mineralize 3,4-DCA. A bacterial co-culture of Arthrobacter sp. N4 and Delftia acidovorans W34, which respectively degraded diuron (20 mg l(-1)) to 3,4-DCA and mineralized 3,4-DCA, were able to mineralize diuron. Total diuron mineralization (20 mg l(-1)) was achieved with free cells in co-culture. When the bacteria were immobilized (either one bacteria or both), the degradation rate was higher. Best results were obtained with free Arthrobacter sp. N4 cells co-cultivated with immobilized cells of D. acidovorans W34 (mineralization of diuron in 96 h, i.e., 0.21 mg l(-1 )h(-1) vs. 0.06 mg l(-1 )h(-1) with free cells in co-culture).

  4. Comparison of the hydrogen-bond patterns in 2-amino-1,3,4-thiadiazolium hydrogen oxalate, 2-amino-1,3,4-thiadiazole-succinic acid (1/2), 2-amino-1,3,4-thiadiazole-glutaric acid (1/1) and 2-amino-1,3,4-thiadiazole-adipic acid (1/1).

    PubMed

    Matulková, Irena; Císařová, Ivana; Němec, Ivan; Fábry, Jan

    2014-10-01

    The X-ray single-crystal structure determinations of the chemically related compounds 2-amino-1,3,4-thiadiazolium hydrogen oxalate, C2H4N3S(+)·C2HO4(-), (I), 2-amino-1,3,4-thiadiazole-succinic acid (1/2), C2H3N3S·2C4H6O4, (II), 2-amino-1,3,4-thiadiazole-glutaric acid (1/1), C2H3N3S·C5H8O4, (III), and 2-amino-1,3,4-thiadiazole-adipic acid (1/1), C2H3N3S·C6H10O4, (IV), are reported and their hydrogen-bonding patterns are compared. The hydrogen bonds are of the types N-H···O or O-H···N and are of moderate strength. In some cases, weak C-H···O interactions are also present. Compound (II) differs from the others not only in the molar ratio of base and acid (1:2), but also in its hydrogen-bonding pattern, which is based on chain motifs. In (I), (III) and (IV), the most prominent feature is the presence of an R2(2)(8) graph-set motif formed by N-H···O and O-H···N hydrogen bonds, which are present in all structures except for (I), where only a pair of N-H···O hydrogen bonds is present, in agreement with the greater acidity of oxalic acid. There are nonbonding S···O interactions present in all four structures. The difference electron-density maps show a lack of electron density about the S atom along the S···O vector. In all four structures, the carboxylic acid H atoms are present in a rare configuration with a C-C-O-H torsion angle of ∼0°. In the structures of (II)-(IV), the C-C-O-H torsion angle of the second carboxylic acid group has the more common value of ∼|180|°. The dicarboxylic acid molecules are situated on crystallographic inversion centres in (II). The Raman and IR spectra of the title compounds are presented and analysed.

  5. 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.

  6. CAF-1-induced oligomerization of histones H3/H4 and mutually exclusive interactions with Asf1 guide H3/H4 transitions among histone chaperones and DNA.

    PubMed

    Liu, Wallace H; Roemer, Sarah C; Port, Alex M; Churchill, Mair E A

    2012-12-01

    Anti-silencing function 1 (Asf1) and Chromatin Assembly Factor 1 (CAF-1) chaperone histones H3/H4 during the assembly of nucleosomes on newly replicated DNA. To understand the mechanism of histone H3/H4 transfer among Asf1, CAF-1 and DNA from a thermodynamic perspective, we developed and employed biophysical approaches using full-length proteins in the budding yeast system. We find that the C-terminal tail of Asf1 enhances the interaction of Asf1 with CAF-1. Surprisingly, although H3/H4 also enhances the interaction of Asf1 with the CAF-1 subunit Cac2, H3/H4 forms a tight complex with CAF-1 exclusive of Asf1, with an affinity weaker than Asf1-H3/H4 or H3/H4-DNA interactions. Unlike Asf1, monomeric CAF-1 binds to multiple H3/H4 dimers, which ultimately promotes the formation of (H3/H4)(2) tetramers on DNA. Thus, transition of H3/H4 from the Asf1-associated dimer to the DNA-associated tetramer is promoted by CAF-1-induced H3/H4 oligomerization.

  7. Transport of 3,4-dihydroxybutyl-1-phosphonate, an analogue of sn-glycerol 3-phosphate.

    PubMed Central

    Leifer, Z; Engel, R; Tropp, B E

    1977-01-01

    3,4-Dihydroxybutyl-1-phosphonate (DHBP), an analogue of glycerol 3-phosphate, is actively transported by the sn-glycerol 3-phosphate transport system of Escherichia coli strain 8. The Km for the transport of DHBP is 200 microM. PMID:400804

  8. POLY-1,2,4-TRIAZOLES AND POLY-1,3,4-OXADIAZOLES FROM PRECURSOR POLY-N-ACYLHYDRAZIDINES,

    DTIC Science & Technology

    oxadiazole . Whereas, conversion of the precursor poly-N-acylhydrazidine predominantly to poly-1,2,4-triazole was affected by refluxing in solvents such... oxadiazole depending upon the heating rate. Poly-N-acylhydrazidine was of sufficient molecular weight to cast a clear yellow film which exhibited good...flexibility. The film, upon thermal treatment to temperatures as high as 300C, became brittle. The poly-1,3,4- oxadiazole and poly-1,2,4-triazole

  9. Synthesis, characterization and stereochemistry of N-acyl-r-2,c-4-bis(4-methoxyphenyl)-3-azabicyclo[3.3.1]nonanes

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    Four new N-acyl-2,4-bis(4-methoxyphenyl)-3-azabicyclo[3.3.1]nonanes 3-6 have been synthesized. The structural characterization and the conformational preferences of the compounds 3-6 have been carried out using IR, 1D and 2D NMR and Mass spectral data. The NMR spectral data indicates that the N-acyl-2,4-bis(4-methoxyphenyl)-3-azabicyclo[3.3.1]nonanes 3-6 prefer to exist in twin-chair conformation with partial flattening at nitrogen end. To avoid A1,3-strain, the anisyl groups at C2 and C4 are forced to occupy the quasi-axial orientation. X-ray crystal structure of the N-dichloroacetyl-2,4-bis(4-methoxyphenyl)-3-azabicyclo[3.3.1]nonane 6 also supports the similar conformation in the solid state.

  10. 1-[2-(4-Chloro­phen­yl)-5-phenyl-2,3-dihydro-1,3,4-oxadiazol-3-yl]ethanone

    PubMed Central

    Fun, Hoong-Kun; Arshad, Suhana; Shyma, P. C.; Kalluraya, Balakrishna; Arulmoli, T.

    2012-01-01

    In the title compound, C16H14ClN3O2, the 2,3-dihydro-1,3,4-oxadiazole ring [maximum deviation = 0.030 (1) Å] and the pyridine ring [maximum deviation = 0.012 (1) Å] are inclined slightly to one another, making a dihedral angle of 11.91 (5)°. The chloro-substituted phenyl ring is almost perpendicular to the 2,3-dihydro-1,3,4-oxadiazole and pyridine rings at dihedral angles of 86.86 (5) and 75.26 (5)°, respectively. In the crystal, π–π [centroid–centroid distance = 3.7311 (6) Å] and C—H⋯π inter­actions are observed. PMID:22719656

  11. INDUCTION AND POST-TRANSCRIPTIONAL SUPPRESSION OF HEPATIC CYTOCHROME P450 1A1 BY 3,3',4,4'-TETRACHLOROBIPHENYL. (R827102)

    EPA Science Inventory

    Abstract

    3,3',4,4'-Tetrachlorobiphenyl (TCB) can induce and inhibit cytochrome P450 1A1 (CYP1A1) in vertebrates. TCB may also suppress CYP1A1 protein levels, but the mechanism is unknown. This study examined transcriptional and translational aspects of hepatic ...

  12. Spectroscopic and laser properties of Er(3+):Yb(3+):LuAl(3)(BO(3))(4) crystal at 1.5-1.6 microm.

    PubMed

    Chen, Yujin; Lin, Yanfu; Huang, Jianhua; Gong, Xinghong; Luo, Zundu; Huang, Yidong

    2010-06-21

    An Er(3+):Yb(3+):LuAl(3)(BO(3))(4) crystal doped with 24.1 at.% Yb(3+) and 1.1 at.% Er(3+) ions was grown by the flux method. The polarized spectroscopic properties related to the operation of 1.5-1.6 microm laser of the crystal were evaluated at room temperature. The laser properties of a 0.7-mm-thick, c-cut crystal were investigated in diode-end-pumped hemispherical and plano-plano cavities, respectively. Compared with those of Er(3+):Yb(3+):YAl(3)(BO(3))(4) crystal obtained under similar experimental conditions, higher maximum output peak power, higher slope efficiency, and lower threshold were achieved in the Er(3+):Yb(3+):LuAl(3)(BO(3))(4) crystal.

  13. [1,2,4]triazolo[4,3-a]phthalazines: inhibitors of diverse bromodomains.

    PubMed

    Fedorov, Oleg; Lingard, Hannah; Wells, Chris; Monteiro, Octovia P; Picaud, Sarah; Keates, Tracy; Yapp, Clarence; Philpott, Martin; Martin, Sarah J; Felletar, Ildiko; Marsden, Brian D; Filippakopoulos, Panagis; Müller, Susanne; Knapp, Stefan; Brennan, Paul E

    2014-01-23

    Bromodomains are gaining increasing interest as drug targets. Commercially sourced and de novo synthesized substituted [1,2,4]triazolo[4,3-a]phthalazines are potent inhibitors of both the BET bromodomains such as BRD4 as well as bromodomains outside the BET family such as BRD9, CECR2, and CREBBP. This new series of compounds is the first example of submicromolar inhibitors of bromodomains outside the BET subfamily. Representative compounds are active in cells exhibiting potent cellular inhibition activity in a FRAP model of CREBBP and chromatin association. The compounds described are valuable starting points for discovery of selective bromodomain inhibitors and inhibitors with mixed bromodomain pharmacology.

  14. [1,2,4]Triazolo[4,3-a]phthalazines: Inhibitors of Diverse Bromodomains

    PubMed Central

    2013-01-01

    Bromodomains are gaining increasing interest as drug targets. Commercially sourced and de novo synthesized substituted [1,2,4]triazolo[4,3-a]phthalazines are potent inhibitors of both the BET bromodomains such as BRD4 as well as bromodomains outside the BET family such as BRD9, CECR2, and CREBBP. This new series of compounds is the first example of submicromolar inhibitors of bromodomains outside the BET subfamily. Representative compounds are active in cells exhibiting potent cellular inhibition activity in a FRAP model of CREBBP and chromatin association. The compounds described are valuable starting points for discovery of selective bromodomain inhibitors and inhibitors with mixed bromodomain pharmacology. PMID:24313754

  15. Synthesis, antityrosinase activity of curcumin analogues, and crystal structure of (1 E,4 E)-1,5-bis(4-ethoxyphenyl)penta-1,4-dien-3-one

    NASA Astrophysics Data System (ADS)

    Chantrapromma, S.; Ruanwas, P.; Boonnak, N.; Chantrapromma, K.; Fun, H.-K.

    2016-12-01

    Five derivatives of curcumin analogue ( R = OCH2CH3 ( 1), R = N(CH3)2 ( 2), R = 2,4,5-OCH3 ( 3), R = 2,4,6-OCH3 ( 4), and R = 3,4,5-OCH3 ( 5)) were synthesized and characterized by 1H NMR, FT-IR and UV-Vis spectroscopy. The synthesized derivatives were screened for antityrosinase activity, and found that 4 and 5 possess such activity. The crystal structure of 1 was determined by single crystal X-ray diffraction: monoclinic, sp. gr. P21/ c, a = 17.5728(15) Å, b = 5.9121(5) Å, c = 19.8269(13) Å, β = 121.155(5)°, Z = 4. The molecule 1 is twisted with the dihedral angle between two phenyl rings being 15.68(10)°. In the crystal packing, the molecules 1 are linked into chains by C-H···π interactions and further stacked by π···π interactions with the centroid-centroid distance of 3.9311(13) Å.

  16. 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...-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1]-4-hydroxy-.kappa.O)-5-nitrobenzenesulfonato(3-)]-, sodium... substance identified as chromate(3-), bis...

  17. 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...-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1]-4-hydroxy-.kappa.O)-5-nitrobenzenesulfonato(3-)]-, sodium... substance identified as chromate(3-), bis...

  18. GDH1 expression is regulated by GLN3, GCN4, and HAP4 under respiratory growth.

    PubMed

    Riego, Lina; Avendaño, Amaranta; DeLuna, Alexander; Rodríguez, Ekaterina; González, Alicia

    2002-04-26

    In the yeast Saccharomyces cerevisiae, two NADP(+)-dependent glutamate dehydrogenase isoenzymes encoded by GDH1 and GDH3 catalyze the synthesis of glutamate from ammonium and alpha-ketoglutarate. In this work we analyzed GDH1 transcriptional regulation, in order to deepen the studies in regard to its physiological role. Our results indicate that: (i) GDH1 expression is strictly controlled in ethanol-grown cultures, constituting a fine-tuning mechanism that modulates the abundance of Gdh1p monomers under this condition, (ii) GDH1 expression is controlled by transcriptional activators that have been considered as exclusive of either nitrogen (Gln3p and Gcn4p) or carbon metabolism (HAP complex), and (iii) chromatin remodeling complexes play a role in GDH1 expression; ADA2 and ADA3 up-regulated GDH1 expression on ethanol, while that on glucose was ADA3-dependent. SPT3 and SNF2 activated GDH1 expression on either carbon source whereas GCN5 played no role in any condition tested. The above described combinatorial control results in a refined mechanism that coordinates carbon and nitrogen utilization.

  19. Synthesis and COX-2 Inhibitory Activity of 4-[(E)-2-(4-Oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethenyl]benzene-1-sulfonamideand Its Analogs

    PubMed Central

    Hayun; Hudiyono, Sumi; Hanafi, Muhammad; Yanuar, Arry

    2012-01-01

    Some novel 3-phenyl-2-[(E)-2-phenylethenyl]-3,4-dihydroquinazolin-4-one derivatives possessing para-sulfonamides groups on the phenyl ring of the 2-phenylethenyl moiety have been synthesized and their COX-2 inhibitory activity evaluated. The stuctures of the synthesized compounds were confirmed on the basis of FT-IR, 1H-NMR, 13C-NMR and mass spectral data. The COX-2 inhibition screening assay revealed that 4-[(E)-2-{3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl}ethenyl]benzene-1-sulfonamide had a maximum COX-2 inhibition (47.1%), at a concentration of 20 μM. PMID:24281337

  20. 1,2,3,3′,4′,6′-Hexaacetyl-4,6-O-benzyl­idenesucrose

    PubMed Central

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

    2011-01-01

    In the title compound, C31H38O17, the 1,3-dioxane and pyran­oside rings both show 4 C 1 chair conformations while for the d-fructofuran­oside 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 pyran­oside ring and axial for the furan­oside ring. The analysis of potential hydrogen bonds shows both intra- and inter­molecular C—H⋯O contacts to be present. PMID:21523142

  1. Crystal structures of four 1-(aryl)-[1,2,4]triazolo[4,3-a]quinoxaline derivatives

    NASA Astrophysics Data System (ADS)

    Nogueira, Thais C. M.; Pinheiro, Alessandra C.; de Souza, Marcus V. N.; Baddeley, Thomas C.; Wardell, James L.; Wardell, Solange M. S. V.

    2017-01-01

    The crystal structures of four 1-aryl-[1,2,4]triazolo[4,3-a]quinoxaline derivatives, 2, are reported: [aryl = 3-ClC6H4: 2a; 2-HOC6H4:2b;2,3-(HO)2C6H3: 2c; and 3,4-(MeO)2C6H3: 2d] The compounds, 2, were prepared by oxidation of substituted arenealdehyde quinoxalin-2-ylhydrazones, 1, using ferric chloride in alcohol. In each of the four compounds, the three ring -[1,2,4]triazolo[4,3-a]quinoxaline moiety is a near planar moiety, with all ring atoms within 0.1 Å of the best plane. There are large dihedral angles, 59 ± 7°, between the [1,2,4]triazolo[4,3-a]quinoxaline system and the phenyl ring. The ortho sited hydroxyl groups in 2c are jointly involved in a single Osbnd H⋯O intramolecular hydrogen bond and individually in Osbnd H⋯N intermolecular interactions, while the hydroxyl group in 2b is involved in an intermolecular Osbnd H⋯N hydrogen bond. These and weaker intermolecular interactions, including some of Csbnd H···Z (Z = O, N and or π) and π···π interactions generate the supramolecular arrangements in 2b and 2c. Intermolecular Csbnd H···Z (Z = O, N and or π) and π···π interactions are only present in 2a and 2d.

  2. Synthesis and theoretical studies of non‒covalent interactions within a newly synthesized chiral 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine

    NASA Astrophysics Data System (ADS)

    Yunus, Uzma; Ahmed, Shahbaz; Chahkandi, Mohammad; Bhatti, Moazzam H.; Tahir, Muhammad Nawaz

    2017-02-01

    In this work the synthesis of a new compound formulated as C12H12N4OS, ((S)-1-(6-Phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)ethanol) (5) reported and theoretical studies of the non‒covalent interactions constructed the related crystalline network described. It has been characterized by IR, Mass, and 1H, 13C NMR spectroscopy and single crystal X‒ray diffraction analysis. The binding energy of the non‒covalent interactions constructing the network of 5 have been calculated by dispersion corrected density functional theory (DFT‒D). The optimization of the formed network using H‒bonding and π‒stacking revealed that 1‒D coordination chain has been composed of neutral monomeric compound. For this purpose, the independent smallest fragment (monomer) and subsequently the related network, including seven monomers, having all non‒covalent interactions have been optimized. The results demonstrate that hydrogen bonds, especially Osbnd H⋯N, Csbnd H⋯O, Csbnd H⋯N, and Csbnd H⋯S interactions, govern the network formation. The calculated results of electronic transition in agreement with the experiment ones show eleven major bands derived from σ → π, n → n/σ*/π* aromatic rings to hydroxyl, inter‒atomic of oxygen, and thiadiazine to phenyl ring charge transfer transitions.

  3. Structures of two precursors to organic charge-transfer salts: 1,3-dithiolo[4,5-b][1,4]dithlin-2-thione and 1,3-dithiolo[4.5-b] [1,4]dithilin-2-one

    SciTech Connect

    Beno, M.A.; Kini, A.M.; Williams, J.M.

    1990-09-01

    C{sub 5}H{sub 4}S{sub 4}O (1), M{sub r} = 208.343, monoclinic, P2{sub 1}/n, a = 6.664 (2), b = 16.535 (6), c = 7.281 (2) {angstrom}, {beta} = 97.84 (3), V = 794.8 (5) {angstrom}{sup 3}, Z = 4, D{sub x} = 1.741 Mg m{sup {minus}3}, {lambda} (MoK{alpha}) = 0.71073 {angstrom}, {mu} = 1.07 mm{sup {minus}1}, F(000) = 424, T = 298 K, R(F) = 0.048 for 2338 reflections. C{sub 5}H{sub 4}S{sub 5} (2), M{sub r} = 224.39, monoclinic, P2{sub 1}/n, a = 10.765 (2), b = 5.879 (2), c = 13.479 (2) {angstrom}, {beta} = 92.66 (2), V = 852.2 (4) {angstrom}{sup 3}, Z = 4, D{sub x} = 1.749 Mg m{sup {minus}3}, {lambda} (MoK{alpha}) = 0. 71073 {angstrom}, {mu} = 1.23 mm{sup {minus}1}, F(000) = 456, T = 298 K, R(F) = 0.059 for 2491 reflections. Structure determinations for intermediates 1 and 2 were undertaken as part of a qualitative theoretical study of the changes in the geometries of organic donor molecules which occur with charge transfer. Although the geometries of 1 and 2 are nearly identical, the packing of these molecules in the unit cells is quite different. The molecular packing patterns are undoubtedly related to differences in the C-H{hor_ellipsis}chalcogen interactions for the thio and keto substituents.

  4. Structure determination of (Fe3O4)n+(n = 1 - 3) 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 = 1 - 3) clusters were obtained by first-principles structural searches. The geometric structures and spin configurations of three cationic (Fe3O4)n+(n = 1 - 3) 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.

  5. Synthesis and antimicrobial activities of some novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines carrying thioalkyl and sulphonyl phenoxy moieties.

    PubMed

    Karabasanagouda, T; Adhikari, Airody Vasudeva; Shetty, N Suchetha

    2007-04-01

    Thirty one new 6-aryl-3-{(4-substituted phenoxy) methyl}-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles (6a-s) and 6-aryl-3-[(4-substituted phenoxy methyl]-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (7a-l) have been synthesized from 4-thioalkyl phenols (1a-b) through a multi-step reaction sequence. Compounds 1a-b reacted with ethyl chloroacetate in presence of acetone and potassium carbonate to give ethyl [4-(thioalkyl) phenoxy] acetates (2a-b). Further, 2a was oxidized to [4-(methyl sulphonyl) phenoxy] acetate (2c) using hydrogen peroxide in acetic acid. Reactions of (2a-c) with hydrazine hydrate in alcoholic medium furnished 2-[4-thiosubstituted phenoxy] acetohydrazides (3a-b) and 2-[4-methyl sulphonyl phenoxy] acetohydrazide (3c) which on treatment with carbon disulphide and methanolic potassium hydroxide yielded corresponding potassium dithiocarbazates (4a-c). They were then converted to 4-amino-5-[(4-thioalkyl phenoxy) methyl]-4H-1,2,4-triazole-3-thiols (5a-b) and 4-amino-5-[(4-methyl sulphonyl phenoxy) methyl]-4H-1,2,4-triazole-3-thiol (5c) by refluxing them with aqueous hydrazine hydrate. The title compounds 6a-s were prepared by condensing 5a-c with various aromatic carboxylic acids in presence of phosphorus oxychloride. The intermediates 5a-c, on condensation with various substituted phenacyl bromides afforded a series of title compounds (7a-l). The structures of new compounds 2a-7l were established on the basis of their elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data. All the title compounds were subjected to in vitro antibacterial testing against four pathogenic strains and antifungal screening against three fungi. Preliminary results indicate that some of them exhibited promising activities and they deserve more consideration as potential antimicrobials.

  6. Synthesis of 1,4-, 2,4-, and 3,4-dimethylphenanthrenes: A novel deoxygenation of arene 1,4-endoxides with trimethylsilyl iodide

    SciTech Connect

    Jung, Keeyong; Koreeda, Masato )

    1989-11-24

    A mild, efficient synthesis of the carcinogen 1,4-dimethylphenanthrene (2) and its bay-region methyl-bearing regioisomers 2,4-dimethyl- and 3,4-dimethylphenanthrenes (3 and 4) is described. The synthesis involves a generally applicable strategy that features a furan/dimethyl-1-naphthyne cycloaddition reaction followed by a convenient direct deoxygenation of the resulting enooxide with excess trimethylsilyl iodide generated in situ. The Friedel-Crafts cyclization of p-xylene with {gamma}-butyrolactone/AlCl{sub 3} or {gamma}-(2,5-dimethylphenyl)butyric acid via its trifluoromethanesulfonic anhydride derivative results in the formation of a mixture of 5,8-, 6,8-, and 5,7-dimethyl-1-tetralones (17, 20, and 21, respectively) through migration of aromatic methyl groups. The precursor to 6,8-dimethyl-1-naphthyne (10) was prepared from tetralone 20, isolable only as a 5:1 inseparable mixture with 17 from the direct Friedel-Crafts cyclization of p-xylene with {gamma}-butyrolactone, by {alpha}-dibromination with CuBr{sub 2}, dehydrobromination, and tosylation. The precursors to 5,8-dimethyl-1-naphthyne (9) and 7,8-dimethyl-1-naphthyne (11) were synthesized from the corresponding 1-naphthols 15 and 31, respectively. The synthesis of these naphthols involved cycloaddition between the corresponding dimethylated benzyne and furan followed by acid-catalyzed isomerization.

  7. 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...

  8. Recombinant β-1,3-1,4-glucanase from Theobroma cacao impairs Moniliophthora perniciosa mycelial growth.

    PubMed

    Britto, Dahyana Santos; Pirovani, Carlos Priminho; Andrade, Bruno Silva; Dos Santos, Tassiara Pereira; Pungartnik, Cristina; Cascardo, Júlio Cezar M; Micheli, Fabienne; Gesteira, Abelmon S

    2013-09-01

    In this work, we identified a gene from Theobroma cacao L. genome and cDNA libraries, named TcGlu2, that encodes a β-1,3-1,4-glucanase. The TcGlu2 ORF was 720 bp in length and encoded a polypeptide of 239 amino acids with a molecular mass of 25.58 kDa. TcGlu2 contains a conserved domain characteristic of β-1,3-1,4-glucanases and presented high protein identity with β-1,3-1,4-glucanases from other plant species. Molecular modeling of TcGlu2 showed an active site of 13 amino acids typical of glucanase with β-1,3 and 1,4 action mode. The recombinant cDNA TcGlu2 obtained by heterologous expression in Escherichia coli and whose sequence was confirmed by mass spectrometry, has a molecular mass of about 22 kDa (with His-Tag) and showed antifungal activity against the fungus Moniliophthora perniciosa, causal agent of the witches' broom disease in cacao. The integrity of the hyphae membranes of M. perniciosa, incubated with protein TcGlu2, was analyzed with propidium iodide. After 1 h of incubation, a strong fluorescence emitted by the hyphae indicating the hydrolysis of the membrane by TcGlu2, was observed. To our knowledge, this is the first study of a cacao β-1,3-1,4-glucanase expression in heterologous system and the first analysis showing the antifungal activity of a β-1,3-1,4-glucanase, in particular against M. perniciosa.

  9. Valence tautomerism of new pyrazolo[4,3-e]tetrazole[4,5-b][1,2,4]triazines

    NASA Astrophysics Data System (ADS)

    Mojzych, Mariusz; Karczmarzyk, Zbigniew; Wysocki, Waldemar; Urbańczyk-Lipkowska, Zofia; Żaczek, Natalia

    2014-06-01

    New pyrazolo[4,3-e]tetrazolo[4,5-b][1,2,4]triazines 5 and 6 were prepared as new biological active compounds with potential anticancer activity referring to our previous study. The 1H NMR spectra reveal tautomeric equilibrium azido and tricyclic forms of these compounds in solution. The molecular and crystal structures of 5 and 6 were determined by the X-ray analysis. The X-ray investigations show that in the crystalline state the compounds 5 and 6 exist as the linear tricyclic pyrazolo[4,3-e]tetrazolo[4,5-b][1,2,4]triazine tautomeric form. The analysis of the intra- and intermolecular interactions indicates the weak C-H⋯N hydrogen bonds and π⋯π interactions in crystal of 6 and van der Waals forces only in crystal of 5 as the non-covalent interactions influencing the molecular packing. The theoretical calculations at the ab initio DFT/B3LYP/6-311++G(d,p) level showed the azido form (3 and 4) as one existing in the gaseous phase and the coexistence of the tricyclic linear (5 and 6) and azido tautomeric forms in solution, wherein the contribution of the linear form compared to the azido form changes with polarity of the solvent.

  10. 4-Methyl-3-(2-phenoxy­acet­yl)-5-phenyl-1,3,4-oxadiazinan-2-one

    PubMed Central

    Zukerman-Schpector, Julio; Sousa Madureira, Lucas; Rodrigues, Alessandro; Vinhato, Elisângela; Olivato, Paulo R.

    2009-01-01

    The 1,3,4-oxadiazinane ring in the title compound, C18H18N2O4, is in a twisted boat conformation. The two carbonyl groups are orientated towards the same side of the mol­ecule. The dihedral angle between the planes of the benzene rings is 76.6 (3)°. Mol­ecules are sustained in the three-dimensional structure by a combination of C—H⋯O, C—H⋯π and π–π [shortest centroid–centroid distance = 3.672 (6) Å] inter­actions. PMID:21582771

  11. 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.

  12. 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.

  13. 3-Benzyl-7-(2,4-dichloro­phen­yl)-4H-1,3,4-thia­diazolo[2,3-c][1,2,4]triazin-4-one

    PubMed Central

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

    2012-01-01

    In the title compound, C17H10Cl2N4OS, 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-thia­diazolo[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 mol­ecules, 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

  14. A facile iodine(III)-mediated synthesis of 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridines via oxidation of 2-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazines and their antimicrobial evaluations

    PubMed Central

    2011-01-01

    Background Fused heterocyclic 1,2,4-triazoles have acquired much importance because of their interesting biological properties. Although a number of methods have been reported in the literature which includes oxidation with phosphorus oxychloride, lead tetraacetate, bromine, etc., hypervalent iodine reagents have emerged as reagents of choice for various synthetically useful transformations due to their low toxicity, ready availability and ease of handling. Results A series of new 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridines 4 has been conveniently synthesized by oxidative cyclization of 2-(3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazines 3 promoted with iodobenzene diacetate under mild conditions (up to 90% isolated yields). All the new compounds were tested in vitro for their antimicrobial activity. Conclusions Iodine(III)-mediated oxidative approach has offered an easy access to new 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridines 4. The antibacterial and antifungal activities of newly synthesized compounds have proved them potent antimicrobial agents. PMID:22373059

  15. 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.

  16. 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.

  17. Reaction of ketones with 1,4-diaza-1,3-diene zirconium and hafnium complexes: First example of a 1,3-dipolar cycloaddition reaction of 1,4-diaza-1,3-diene complexes of early transition metals

    SciTech Connect

    Scholz, J.; Goerls, H.

    1996-07-17

    The chemical preparation of M[O(R)PhCH(CH{double_bond}N(tBu))N(tBu)]{sub 2} (M = Zr, R = Me (4a), R = Ph (4b) and M = Hf, R = Me (5a), R = Ph (5b)) complexes is described. The reaction can be described as a 1,3-dipolar cycloaddition of C{double_bond}O across the M-N-C portion of Zr and Hf 1,4-diaza-1,3-diene complexes. The crystal structures of 4a and 5b are reported.

  18. Regioselective synthesis of 2-amino-substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives via reagent-based cyclization of thiosemicarbazide intermediate.

    PubMed

    Yang, Seung-Ju; Lee, Seok-Hyeong; Kwak, Hyun-Jung; Gong, Young-Dae

    2013-01-18

    A regioselective, reagent-based method for the cyclization reaction of 2-amino-1,3,4-oxadiazole and 2-amino-1,3,4-thiadiazole core skeletons is described. The thiosemicarbazide intermediate 3 was reacted with EDC·HCl in DMSO or p-TsCl, triethylamine in N-methyl-2-pyrrolidone to give the corresponding 2-amino-1,3,4-oxadiazoles 4 and 2-amino-1,3,4-thiadiazoles 5 through regioselcective cyclization processes. The regioselectivity was affected by both R(1) and R(2) in p-TsCl mediated cyclization. It is shown in select sets of thiosemicarbazide 3 with R(1)(benzyl) and R(2)(phenyl). 2-Amino-1,3,4-oxadiazole 4 was also shown in the reaction of p-TsCl mediated cyclization. The resulting 2-amino-1,3,4-oxadiazole and 2-amino-1,3,4-thiadiazole core skeleton are functionalized with various electrophiles such as alkyl halide, acid halides, and sulfornyl chloride in high yields.

  19. 4-cholesten-3-one suppresses lung adenocarcinoma metastasis by regulating translocation of HMGB1, HIF1α and Caveolin-1

    PubMed Central

    Ma, Jinben; Fu, Guobin; Wu, Jing; Han, Shaoxian; Zhang, Lishan; Yang, Ming; Yu, Yong; Zhang, Mengyuan; Lin, Yanliang; Wang, Yibing

    2016-01-01

    Metastasis is a great challenge in lung adenocarcinoma (ADC) therapy. Cholesterol has been implicated in ADC metastasis. 4-cholesten-3-one, as cholesterol metabolite and analog, can substitute membrane cholesterol and increase membrane fluidity. In this study, we explored the possibility that 4-cholesten-3-one inhibited ADC metastasis. Low-dose 4-cholesten-3-one significantly restrained ADC cells migration and invasion with little effects on cells viabilities. Further investigation showed that 4-cholesten-3-one promoted ROS generation, which transiently activated AMPKα1, increased HIF1α expression, reduced Bcl-2 expression and caused autophagy. AMPKα1 knockdown partly suppressed 4-cholesten-3-one-induced autophagy but, neither prevented 4-cholesten-3-one-induced upregulation of HIF1α or downregulation of Bcl-2. 4-cholesten-3-one-induced autophagy facilitated the release of HMGB1 from nuclei to cytoplasm, blocking nuclear translocation of HIF1α and activation of MMP2 and MMP9. Also, 4-cholesten-3-one induced time-dependent phosphorylation of caveolin-1, Akt and NF-κB. With increasing treatment time, 4-cholesten-3-one accelerated caveolin-1 internalization, but reduced the phosphorylation of Akt and NF-κB, and inhibited the expression of snail and twist. These data suggested that 4-cholesten-3-one could be a potential candidate for anti-metastasis of lung adenocarcinoma. PMID:27899819

  20. 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.

  1. Sonochemical synthesis of novel pyrano[3,4-e][1,3]oxazines: A green protocol.

    PubMed

    Saleh, Tamer S; Al-Bogami, Abdullah S; Mekky, Ahmed E M; Alkhathlan, Hamad Z

    2017-05-01

    The atom-efficient and green protocol for formation of pyrano[3,4-e][1,3]oxazines utilizing dimethyl carbonate under ultrasound irradiation in a presence of KF/basic alumina was reported. We provide a novel series of pyrano[3,4-e][1,3]oxazine derivatives interesting for biological screening tests. In general, it was found that ultrasound irradiations enable the reactions to occur which could not be carried out under silent conditions. These remarkable effects appeared in sonicated reactions can be reasonably interpreted in terms of acoustic cavitation phenomenon. Structures of the products were established on analytical and spectral data. This protocol offers several advantages attain many principles of green chemistry including, save energy, atom economy, clean reactions, inexpensive green reagent and use catalysts rather than stoichiometric reagents.

  2. 1,4-Bis(4-bromo-2,6-diisopropyl­phen­yl)-1,4-diaza­buta-1,3-diene

    PubMed Central

    Guzei, Ilia A.; Hill, Nicholas J.; Van Hout, Matthew R.

    2010-01-01

    The molecule of the title compound, C26H34Br2N2, lies on a crystallographic inversion center and hence the two imine groups are s-trans. The dihedral angle between the central 1,4-diaza­buta-1,3-diene unit and the attached substituted phenyl ring is 88.4 (7)°. The structure features a C—H⋯N close contact. The crystal selected for this study proved to be a non-merohedral twin with a minor component of 21.8 (3)%. PMID:21580146

  3. Role of (1,3)(1,4)-β-glucan in cell walls: interaction with cellulose.

    PubMed

    Kiemle, Sarah N; Zhang, Xiao; Esker, Alan R; Toriz, Guillermo; Gatenholm, Paul; Cosgrove, Daniel J

    2014-05-12

    (1,3)(1,4)-β-D-Glucan (mixed-linkage glucan or MLG), a characteristic hemicellulose in primary cell walls of grasses, was investigated to determine both its role in cell walls and its interaction with cellulose and other cell wall polysaccharides in vitro. Binding isotherms showed that MLG adsorption onto microcrystalline cellulose is slow, irreversible, and temperature-dependent. Measurements using quartz crystal microbalance with dissipation monitoring showed that MLG adsorbed irreversibly onto amorphous regenerated cellulose, forming a thick hydrogel. Oligosaccharide profiling using endo-(1,3)(1,4)-β-glucanase indicated that there was no difference in the frequency and distribution of (1,3) and (1,4) links in bound and unbound MLG. The binding of MLG to cellulose was reduced if the cellulose samples were first treated with certain cell wall polysaccharides, such as xyloglucan and glucuronoarabinoxylan. The tethering function of MLG in cell walls was tested by applying endo-(1,3)(1,4)-β-glucanase to wall samples in a constant force extensometer. Cell wall extension was not induced, which indicates that enzyme-accessible MLG does not tether cellulose fibrils into a load-bearing network.

  4. 1,4-Diiodo-1,3-dienes: versatile reagents in organic synthesis.

    PubMed

    Ananikov, Valentine P; Hazipov, Oleg V; Beletskaya, Irina P

    2011-02-01

    1,4-Diiodo-1,3-dienes are unique reagents in organic synthesis and have been employed in several well-known and recently developed areas of application. Furthermore, these dienes are easily accessible, starting from the alkynes and iodine, and they have demonstrated high reactivity in cross-coupling reactions, organometallic synthesis, in the preparation of heterocyclic compounds, and several other transformations. The high reactivity of the 1,4-diiodo-1,3-dienes allows for the development of synthetic procedures that use mild conditions (room temperature). The key advantages in assembling complex organic molecules, natural products, and compounds for material science using 1,4-diiodo-1,3-dienes as building blocks include high yields, excellent selectivity, and diverse reactivity in carbon-carbon and carbon-heteroatom bond formation. This Focus Review describes the scope and application of the 1,4-diiodo-1,3-dienes in organic synthesis as well as summarizes the methods for preparation of the dienes.

  5. (3-aminopropyl)-4-methylpiperazine end-capped poly(1,4-butanediol diacrylate-co-4-amino-1-butanol)-based multilayer films for gene delivery.

    PubMed

    Li, Cuicui; Tzeng, Stephany Y; Tellier, Liane E; Green, Jordan J

    2013-07-10

    Biodegradable polyelectrolyte surfaces for gene delivery were created through electrospinning of biodegradable polycations combined with iterative solution-based multilayer coating. Poly(β-amino ester) (PBAE) poly(1,4-butanediol diacrylate-co-4-amino-1-butanol) end-capped with 1-(3-aminopropyl)-4-methylpiperazine was utilized because of its ability to electrostatically interact with anionic molecules like DNA, its biodegradability, and its low cytotoxicity. A new DNA release system was developed for sustained release of DNA over 24 h, accompanied by high exogenous gene expression in primary human glioblastoma (GB) cells. Electrospinning a different PBAE, poly(1,4-butanediol diacrylate-co-4,4'-trimethylenedipiperidine), and its combination with polyelectrolyte 1-(3-aminopropyl)-4-methylpiperazine end-capped poly(1,4-butanediol diacrylate-co-4-amino-1-butanol)-based multilayers are promising for DNA release and intracellular delivery from a surface.

  6. 1,4-Dimethyl-3-phenyl-3H-pyrazolo[3,4-c]isoquinolin-5(4H)-one.

    PubMed

    Meneghetti, Fiorella; Bombieri, Gabriella; Maggio, Benedetta; Daidone, Giuseppe

    2008-04-16

    The title compound, C(18)H(15)N(3)O, is the product of the thermal decomposition of the diazo-nium salt derived from 2-amino-N-methyl-N-(3-methyl-1-phenyl-1H-pyrazol-5-yl)benzamide. It is characterized by a trans orientation of the methyl groups with respect to the tricyclic ring system. The mol-ecule has a nearly planar phenyl-pyrazolo[3,4-c]isoquinolin-5-one system, the largest deviation from the mean plane being 0.066 (2) Å for the O atom. The dihedral angle between the phenyl substituent and the heterotricycle is 67 (1)°. The packing is stabilized by C-H⋯N hydrogen-bond inter-actions, with the formation of mol-ecular chains along the c axis.

  7. Stereoselectivity of a potent calcium antagonist, 1-benzyl-3-pyrrolidinyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

    PubMed

    Tamazawa, K; Arima, H; Kojima, T; Isomura, Y; Okada, M; Fujita, S; Furuya, T; Takenaka, T; Inagaki, O; Terai, M

    1986-12-01

    Four enantiomers (3a-d) of the title compound, YM-09730 (3), were synthesized by the reaction of (-)- or (+)-5-(methoxycarbonyl)-2, 6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1a or 1b) with (S)- or (R)-1-benzyl-3-pyrrolidinol (2a or 2b). [3H]Nitrendipine binding affinity and coronary vasodilating activity of these compounds were evaluated. The absolute configuration of the most potent enantiomer (3a) with the longest duration was unequivocally determined to be (S)-1,4-dihydropyridine-C4 and (S)-pyrrolidine-C3 (S,S) by X-ray crystallographic study on 3a X HBr as well as 3a X HCl. The configuration of 1a corresponds to R, and the other enantiomers of 3 were respectively determined by chemical correlation. The potency order of the four enantiomers was (S,S)-3a greater than (S,R)-3b greater than (R,R)-3d greater than (R,S)-3c. Latent chiral characters of nifedipine derivatives with the identical ester groups were assigned by comparison of their puckering modes of 1,4-dihydropyridine (DHP) rings with those found in 3a X HCl or 3a X HBr. On the basis of the assignment, it has been revealed that the (S)-DHP nifedipine derivatives possess the synperiplanar carbonyl group at C5. The conformational restriction may be a factor causing stereoselectivity of antagonism.

  8. A novel IRS-1-associated protein, DGKζ regulates GLUT4 translocation in 3T3-L1 adipocytes.

    PubMed

    Liu, TingYu; Yu, BuChin; Kakino, Mamoru; Fujimoto, Hitoshi; Ando, Yasutoshi; Hakuno, Fumihiko; Takahashi, Shin-Ichiro

    2016-10-14

    Insulin receptor substrates (IRSs) are major targets of insulin receptor tyrosine kinases. Here we identified diacylglycerol kinase zeta (DGKζ) as an IRS-1-associated protein, and examined roles of DGKζ in glucose transporter 4 (GLUT4) translocation to the plasma membrane. When DGKζ was knocked-down in 3T3-L1 adipocytes, insulin-induced GLUT4 translocation was inhibited without affecting other mediators of insulin-dependent signaling. Similarly, knockdown of phosphatidylinositol 4-phosphate 5-kinase 1α (PIP5K1α), which had been reported to interact with DGKζ, also inhibited insulin-induced GLUT4 translocation. Moreover, DGKζ interacted with IRS-1 without insulin stimulation, but insulin stimulation decreased this interaction. Over-expression of sDGKζ (short-form DGKζ), which competed out DGKζ from IRS-1, enhanced GLUT4 translocation without insulin stimulation. Taking these results together with the data showing that cellular PIP5K activity was correlated with GLUT4 translocation ability, we concluded that IRS-1-associated DGKζ prevents GLUT4 translocation in the absence of insulin and that the DGKζ dissociated from IRS-1 by insulin stimulation enhances GLUT4 translocation through PIP5K1α activity.

  9. A novel IRS-1-associated protein, DGKζ regulates GLUT4 translocation in 3T3-L1 adipocytes

    PubMed Central

    Liu, TingYu; Yu, BuChin; Kakino, Mamoru; Fujimoto, Hitoshi; Ando, Yasutoshi; Hakuno, Fumihiko; Takahashi, Shin-Ichiro

    2016-01-01

    Insulin receptor substrates (IRSs) are major targets of insulin receptor tyrosine kinases. Here we identified diacylglycerol kinase zeta (DGKζ) as an IRS-1-associated protein, and examined roles of DGKζ in glucose transporter 4 (GLUT4) translocation to the plasma membrane. When DGKζ was knocked-down in 3T3-L1 adipocytes, insulin-induced GLUT4 translocation was inhibited without affecting other mediators of insulin-dependent signaling. Similarly, knockdown of phosphatidylinositol 4-phosphate 5-kinase 1α (PIP5K1α), which had been reported to interact with DGKζ, also inhibited insulin-induced GLUT4 translocation. Moreover, DGKζ interacted with IRS-1 without insulin stimulation, but insulin stimulation decreased this interaction. Over-expression of sDGKζ (short-form DGKζ), which competed out DGKζ from IRS-1, enhanced GLUT4 translocation without insulin stimulation. Taking these results together with the data showing that cellular PIP5K activity was correlated with GLUT4 translocation ability, we concluded that IRS-1-associated DGKζ prevents GLUT4 translocation in the absence of insulin and that the DGKζ dissociated from IRS-1 by insulin stimulation enhances GLUT4 translocation through PIP5K1α activity. PMID:27739494

  10. 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

  11. 3,6-Bis(2-pyridyl)di-1,2,4-triazolo[3,4-a:4',3'-c]phthalazine.

    PubMed

    Chang, Wen-Fu; Wen, Yuh-Sheng; Liu, Ling-Kang

    2004-09-01

    The title compound, C20H12N8, (I), has been prepared by the reaction of 1,4-dihydrazinophthalazine and pyridine-2-carboxaldehyde, followed by an oxidative cyclization by treatment with bromine. In the solid state, the molecules of (I) are discrete, comprising a fused and twisted four-ring system with an overall helical appearance. The distance between the two intramolecular pyridyl N atoms is 3.075 (2) A, this short contact distance suggesting a pi-pi interaction.

  12. Synthesis of (3S,4S)-4-aminopyrrolidine-3-ol derivatives and biological evaluation for their BACE1 inhibitory activities.

    PubMed

    De Tran, Quang; Bepary, Sukumar; Lee, Ge Hyeong; Cho, Heeyeong; Park, Woo Kyu; Lim, Hee-Jong

    2016-01-01

    Synthesis, SAR study and BACE1 inhibitory activity of (3S,4S)-4-aminopyrrolidine-3-ol derivatives (2) were described. The compound 7c exhibited more inhibition activity than 11a (IC50: 0.05μM vs 0.12μM, respectively), but the latter was more effective in cell-based assay (IC50: 1.7μM vs 40% inhibition by 7c @ 10μM) due to the relatively higher cell permeability. Most of the compounds showed high selectivity over BACE2 and cathepsin D. This work will provide useful information for further structural modifications to develop potent BACE1 inhibitors in cell.

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. Synthesis and antioxidant activity of novel Mannich base of 1,3,4-oxadiazole derivatives possessing 1,4-benzodioxan.

    PubMed

    Ma, Liang; Xiao, Yu; Li, Cong; Xie, Zheng-Lu; Li, Dong-Dong; Wang, Yan-Ting; Ma, Hai-Tian; Zhu, Hai-Liang; Wang, Ming-Hua; Ye, Yong-Hao

    2013-11-01

    A new series of Mannich base of 1,3,4-oxadiazole derivatives possessing 1,4-benzodioxan (6a-6ae) were synthesized and characterized by (1)H NMR, ESI-MS and elemental analysis. The structure of 6b was further confirmed by single crystal X-ray diffraction. All these novel compounds were screened for their in vitro antioxidant activity employing 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+)) and ferric reducing antioxidant power (FRAP) scavenging assays. Due to the combination of 1,4-benzodioxan, 1,3,4-oxadiazoles and substituted phenyl ring, most of them exhibited nice antioxidant activities. In all of these three assays mentioned above, compounds 6f and 6e showed significant radical scavenging ability comparable to the commonly used antioxidants, BHT and Trolox. Seven compounds with representative substituents or activities were selected for further assays in chemical simulation biological systems-inhibition of microsomal lipid peroxidation (LPO) and protection against 2,2'-azobis (2-amidinopropane hydrochloride) (AAPH) induced DNA strand breakage, in which, 6f and 6e were demonstrated to be of the most potent antioxidant activities.

  19. 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

  20. 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.

  1. Enzymatic conjugation of hexachloro-1,3-butadiene with glutathione. Formation of 1-(glutathion-S-yl)-1,2,3,4,4-pentachlorobuta-1,3-diene and 1,4-bis(glutathion-S-yl)-1,2,3,4-tetrachlorobuta-1,3-diene.

    PubMed

    Dekant, W; Vamvakas, S; Henschler, D; Anders, M W

    1988-01-01

    The glutathione-dependent metabolism of the nephrotoxin and nephrocarcinogen hexachloro-1,3-butadiene (HCBD) was investigated in subcellular fractions from rat liver and kidney. HCBD was metabolized by hepatic glutathione S-transferases to (E)- and (Z)-1-(glutathion-S-yl)-pentachlorobuta-1,3-diene (GPCB) in a ratio of 20:1, which were identified by secondary ion MS and by GC-MS after acid hydrolysis. The formation of GPCB was dependent on time and on protein and glutathione concentrations. Microsomal glutathione S-transferases from rat liver catalyzed GPCB formation more efficiently than did cytosolic glutathione S-transferases; very low rates of GPCB formation were observed in kidney subcellular fractions. GPCB is also a substrate for glutathione S-transferases and is metabolized to a diglutathione conjugate, which was identified by secondary ion MS and 13C NMR spectrometry as 1,4-bis(glutathion-S-yl)-1,2,3,4-tetrachlorobuta-1,3-diene (BTCB). BTCB formation from GPCB was dependent on time and on protein, glutathione, and GPCB concentrations. Hepatic cytosol catalyzed BTCB formation more efficiently than did hepatic microsomes; significant amounts of BTCB were also formed in kidney cytosol. Hepatic formation of glutathione S-conjugates, translocation of the S-conjugates to the kidney, and renal processing to form reactive intermediates may be the cause of HCBD-induced nephrotoxicity and, perhaps, nephrocarcinogenicity.

  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. Ultrasound-mediated synthesis of 4-substituted 1,4-dihydropyridine-3,5-dicarboxylates catalyzed by 1-carboxymethyl-3-methylimidazolium tetrafluoroborate under solvent free condition.

    PubMed

    He, Jing-Yu; Jia, Hui-Zhen; Yao, Qing-Guo; Liu, Si-Jie; Yue, Hong-Kun; Yu, Hong-Wei; Hu, Rui-Sheng

    2015-01-01

    4-Substituted 1,4-dihydropyridine-3,5-dicarboxylates (4) have been synthesized by the solvent-free reaction of aldehyde, methyl propiolate and ammonium carbonate catalyzed by ionic liquid 1-carboxymethyl-3-methylimidazolium tetrafluoroborate under ultrasonic irradiation. The effects of changes in the ultrasonic power, temperature, catalysts and reactants on the synthesis of 4-substituted 1,4-dihydropyridine-3,5-dicarboxylates (4) are discussed. With the optimized reaction conditions, various aldehydes were used to synthesize 1,4-dihydropyridines (4) under the influence of ultrasound irradiation. Compared with the conventional thermal methods, the remarkable advantages of this method are the simple experimental procedure, shorter reaction time (2-10min) and high yield of product (76-95%). Furthermore, the green catalytic system can be recycled specific times without significantly decreasing the yields and reaction rates.

  4. 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.

  5. 40 CFR 721.10162 - 1,3 Dioxolane-4-butanol, 2-ethenyl-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1,3 Dioxolane-4-butanol, 2-ethenyl... Specific Chemical Substances § 721.10162 1,3 Dioxolane-4-butanol, 2-ethenyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 1,3 dioxolane-4-butanol,...

  6. 40 CFR 721.10162 - 1,3 Dioxolane-4-butanol, 2-ethenyl-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 1,3 Dioxolane-4-butanol, 2-ethenyl... Specific Chemical Substances § 721.10162 1,3 Dioxolane-4-butanol, 2-ethenyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 1,3 dioxolane-4-butanol,...

  7. 40 CFR 721.10162 - 1,3 Dioxolane-4-butanol, 2-ethenyl-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 1,3 Dioxolane-4-butanol, 2-ethenyl... Specific Chemical Substances § 721.10162 1,3 Dioxolane-4-butanol, 2-ethenyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 1,3 dioxolane-4-butanol,...

  8. 40 CFR 721.10162 - 1,3 Dioxolane-4-butanol, 2-ethenyl-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 1,3 Dioxolane-4-butanol, 2-ethenyl... Specific Chemical Substances § 721.10162 1,3 Dioxolane-4-butanol, 2-ethenyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 1,3 dioxolane-4-butanol,...

  9. 40 CFR 721.10162 - 1,3 Dioxolane-4-butanol, 2-ethenyl-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false 1,3 Dioxolane-4-butanol, 2-ethenyl... Specific Chemical Substances § 721.10162 1,3 Dioxolane-4-butanol, 2-ethenyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 1,3 dioxolane-4-butanol,...

  10. Refined Synthesis of 2,3,4,5-Tetrahydro-1,3,3-trimethyldipyrrin, a Deceptively Simple Precursor to Hydroporphyrins

    PubMed Central

    Ptaszek, Marcin; Bhaumik, Jayeeta; Kim, Han-Je; Taniguchi, Masahiko; Lindsey, Jonathan S.

    2008-01-01

    2,3,4,5-Tetrahydro-1,3,3-trimethyldipyrrin (1) is a crucial building block in the rational synthesis of chlorins and oxochlorins. The prior 5-step synthesis of 1 from pyrrole-2-carboxaldehyde (2) employed relatively simple and well-known reactions yet suffered from several drawbacks, including limited scale (≥ 0.5 g of 1 per run). A streamlined preparation of 1 has been developed that entails four steps: (i) nitro-aldol condensation of 2 and nitromethane under neat conditions to give 2-(2-nitrovinyl)pyrrole (3), (ii) reduction of 3 with NaBH4 to give 2-(2-nitroethyl)pyrrole (4), (iii) Michael addition of 4 with mesityl oxide under neat conditions or at high concentration to give γ-nitrohexanonepyrrole 5, and (iv) reductive cyclization of 5 with zinc/ammonium formate to give 1. Several multistep transformations have been established, including the direct conversion of 2 → 1. The advantages of the new procedures include (1) fewer steps, (2) avoidance of several problematic reagents, (3) diminished consumption of solvents and reagents, (4) lessened reliance on chromatography, and (5) scalability. The new procedures facilitate the preparation of 1 at the multigram scale. PMID:19132135

  11. Synthesis of [3 alpha-3H]7-dehydrocholesterol via stable tritiated 4-phenyl-1,2,4-triazoline-3,5-dione derivative.

    PubMed

    Batta, A K; Salen, G; Tint, G S; Honda, A; Shefer, S

    1997-11-01

    Synthesis of [3 alpha-3H]7-dehydrocholesterol is described via protection of the 5,7-diene system in 7-dehydrocholesterol as the Diels-Alder adduct with 4-phenyl-1,2,4-triazoline-3,5-dione followed by oxidation of the hydroxyl group to give the 3-oxo adduct. Reduction of the keto adduct with [3H]sodium borohydride produced the adduct of [3 alpha-3H]7-dehydrocholesterol from which the radiolabeled sterol was obtained via treatment with lithium aluminum hydride. The advantage of the method is that highly labeled [3 alpha-3H]7-dehydrocholesterol can be prepared. Further, unlike 7-dehydrocholesterol, its adduct with 4-phenyl-1,2,4-triazoline-3,5-dione is stable and can be stored. This allows the preparation of small batches of [3 alpha-3H]7-dehydrocholesterol for immediate use in biological experiments, and losses due to decomposition of excess radiolabeled 7-dehydrocholesterol are minimized.

  12. Formation of a highly stable complex between BN 50730 [tetrahydro-4,7,8,10 methyl-1(chloro-2 phenyl)-6 (methoxy-4 phenyl-carbamoyl)-9 pyrido [4',3'-4,5] thieno [3,2-f] triazolo-1,2,4 [4,3-a] diazepine-1,4] and the platelet-activating factor receptor in rabbit platelet membranes.

    PubMed

    Silva, C L; Cruz, H N; Violante, F A; Cordeiro, R S; Martins, M A; Noël, F

    1996-01-26

    BN 50730 [tetrahydro-4,7,8,10 methyl-1(chloro-2 phenyl)-6 (methoxy-4 phenyl-carbamoyl)-9 pyrido [4',3'-4,5] thieno [3,2-f] triazolo-1,2,4 [4,3-alpha] diazepine-1,4], a novel platelet-activating factor (PAF) receptor antagonist with a hetrazepine structure, decreased the maximal number of binding sites (Bmax) of [3H]PAF in rabbit platelet membranes without altering its dissociation constant. Platelet aggregation induced by 1 microM PAF was prevented by preincubation with 1 microM BN 50730. The washing of the platelets preincubated with BN 50730 failed to revert its inhibitory effects. We conclude that BN 50730 acts as a non-competitive antagonist of the PAF receptor, due to the formation of a highly stable drug-receptor complex.

  13. 42 CFR 84.100 - Man tests 1, 2, 3, and 4; requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...-Contained Breathing Apparatus § 84.100 Man tests 1, 2, 3, and 4; requirements. Man tests 1, 2, 3, and 4, set... of work and physical orientation; and (d) Provide information on the operating and...

  14. 42 CFR 84.100 - Man tests 1, 2, 3, and 4; requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...-Contained Breathing Apparatus § 84.100 Man tests 1, 2, 3, and 4; requirements. Man tests 1, 2, 3, and 4, set... of work and physical orientation; and (d) Provide information on the operating and...

  15. 42 CFR 84.100 - Man tests 1, 2, 3, and 4; requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...-Contained Breathing Apparatus § 84.100 Man tests 1, 2, 3, and 4; requirements. Man tests 1, 2, 3, and 4, set... of work and physical orientation; and (d) Provide information on the operating and...

  16. 42 CFR 84.100 - Man tests 1, 2, 3, and 4; requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...-Contained Breathing Apparatus § 84.100 Man tests 1, 2, 3, and 4; requirements. Man tests 1, 2, 3, and 4, set... of work and physical orientation; and (d) Provide information on the operating and...

  17. 42 CFR 84.100 - Man tests 1, 2, 3, and 4; requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...-Contained Breathing Apparatus § 84.100 Man tests 1, 2, 3, and 4; requirements. Man tests 1, 2, 3, and 4, set... of work and physical orientation; and (d) Provide information on the operating and...

  18. Investigation of 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one: Crystal structure, AIM and NBO analysis

    NASA Astrophysics Data System (ADS)

    Udayakumar, Mani; Jagatheeswaran, Kothandapani; Ganesan, Subramaniapillai Selva; Venkataramanan, Natarajan S.; Madan Kumar, Shankar; Byrappa, Kullaiah; Thamotharan, Subbiah

    2017-04-01

    Single crystal X-ray analysis reveals that the 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one, crystallizes in the centrosymmetric space group P21/c. In the crystal, molecules form as a dimer through a keto-enol type hydrogen-bonding pattern along with intermolecular Csbnd H⋯O interactions. The crystal structure of the title compound is further stabilized by intermolecular H⋯H interactions. Various intermolecular interactions present in the crystal structure are quantified by Hirshfeld surface analysis, PIXEL energy, NBO, AIM and DFT calculations. The energetics of the title compound is also compared with that of the two closely related analogs. Further, the vibrational modes of the interacting groups are characterized using both the experimental and simulated FT-IR and FT-Raman spectra. The experimental and calculated UV-visible spectra are compared and agree well. The time-dependent DFT spectra suggest that the ligand-to-ligand charge transfer within the molecule is responsible for the intense absorbance.

  19. Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes.

    PubMed

    Mitsuhashi, Kazuteru; Senmaru, Takafumi; Fukuda, Takuya; Yamazaki, Masahiro; Shinomiya, Katsuhiko; Ueno, Morio; Kinoshita, Shigeru; Kitawaki, Jo; Katsuyama, Masato; Tsujikawa, Muneo; Obayashi, Hiroshi; Nakamura, Naoto; Fukui, Michiaki

    2016-01-01

    Decreases in serum testosterone concentrations in aging men are associated with metabolic disorders. Testosterone has been reported to increase GLUT4-dependent glucose uptake in skeletal muscle cells and cardiomyocytes. However, studies on glucose uptake occurring in response to testosterone stimulation in adipocytes are currently not available. This study was designed to determine the effects of testosterone on glucose uptake in adipocytes. Glucose uptake was assessed with 2-[(3)H] deoxyglucose in 3T3-L1 adipocytes. GLUT4 translocation was evaluated in plasma membrane (PM) sheets and PM fractions by immunofluorescence and immunoblotting, respectively. Activation of GLUT4 translocation-related protein kinases, including Akt, AMPK, LKB1, CaMKI, CaMKII, and Cbl was followed by immunoblotting. Expression levels of androgen receptor (AR) mRNA and AR translocation to the PM were assessed by real-time RT-PCR and immunoblotting, respectively. The results showed that both high-dose (100 nM) testosterone and testosterone-BSA increased glucose uptake and GLUT4 translocation to the PM, independently of the intracellular AR. Testosterone and testosterone-BSA stimulated the phosphorylation of AMPK, LKB1, and CaMKII. The knockdown of LKB1 by siRNA attenuated testosterone- and testosterone-BSA-stimulated AMPK phosphorylation and glucose uptake. These results indicate that high-dose testosterone and testosterone-BSA increase GLUT4-dependent glucose uptake in 3T3-L1 adipocytes by inducing the LKB1/AMPK signaling pathway.

  20. 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.

  1. Fused polycyclic compounds via cycloaddition of 4-(1'-cyclohexenyl)-5-iodo-1,2,3-triazoles with 4-phenyl-1,2,4-triazoline-3,5-dione: the importance of a sacrificial iodide leaving group.

    PubMed

    Michaels, Heather A; Simmons, J Tyler; Clark, Ronald J; Zhu, Lei

    2013-05-17

    4-(1'-Cyclohexenyl)-5-iodo-1,2,3-triazole and 4-phenyl-1,2,4-triazoline-3,5-dione undergo a formal Diels-Alder reaction, which following an S(N)2' solvolysis process to displace the iodo group affords a fused polycyclic compound.

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

    PubMed

    Śmist, Małgorzata; Kwiecień, Halina; Krawczyk, Maria

    2016-01-01

    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%).

  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. 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.

  5. The absolute configuration of (2S,4S)- and (2R,4R)-2-tert-butyl-4-methyl-3-(4-tolylsulfonyl)-1,3-oxazolidine-4-carbaldehyde.

    PubMed

    Flock, Susanne; Bruhn, Clemens; Fink, Heinrich; Frauenrath, Herbert

    2006-02-01

    The title enantiomorphic compounds, C16H23NO4S, have been obtained in an enantiomerically pure form by crystallization from a diastereomeric mixture either of (2S,4S)- and (2R,4S)- or of (2R,4R)- and (2S,4R)-2-tert-butyl-4-methyl-3-(4-tolylsulfonyl)-1,3-oxazolidine-4-carbaldehyde. These mixtures were prepared by an aziridination rearrangement process starting with (S)- or (R)-2-tert-butyl-5-methyl-4H-1,3-dioxine. The crystal structures indicate an envelope conformation of the oxazolidine moiety for both compounds.

  6. Synthesis and multi-spectroscopic DNA binding study of 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives of fatty acid

    NASA Astrophysics Data System (ADS)

    Hassan, Mohammad F.; Rauf, Abdul

    2016-01-01

    A facile and convenient synthesis of a series of fatty acid derivatives of 1,3,4-oxadiazole and 1,3,4-thiadiazole has been described. The key step of this protocol is the cyclization of acyl thiosemicarbazides via iodobenzene diacetate and methanesulfonic acid under mild conditions. The newly synthesized compounds were characterized by FT-IR, 1HNMR, 13CNMR and mass spectral study. The binding affinity of 5-(pentadecyl)-N-propenyl-1,3,4-oxadiazol-2-amine (3a) and 5-(heptadecyl)-2-amino-1,3,4-thiadiazole (6a) with CT-DNA has been evaluated by UV, fluorescence, Circular Dichroism (CD) and thermal denaturation studies. It has been found that these small and planer heteroaromatic compounds are capable of binding to the minor groove region of DNA.

  7. Synthesis and multi-spectroscopic DNA binding study of 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives of fatty acid.

    PubMed

    Hassan, Mohammad F; Rauf, Abdul

    2016-01-15

    A facile and convenient synthesis of a series of fatty acid derivatives of 1,3,4-oxadiazole and 1,3,4-thiadiazole has been described. The key step of this protocol is the cyclization of acyl thiosemicarbazides via iodobenzene diacetate and methanesulfonic acid under mild conditions. The newly synthesized compounds were characterized by FT-IR, (1)HNMR, (13)CNMR and mass spectral study. The binding affinity of 5-(pentadecyl)-N-propenyl-1,3,4-oxadiazol-2-amine (3a) and 5-(heptadecyl)-2-amino-1,3,4-thiadiazole (6a) with CT-DNA has been evaluated by UV, fluorescence, Circular Dichroism (CD) and thermal denaturation studies. It has been found that these small and planer heteroaromatic compounds are capable of binding to the minor groove region of DNA.

  8. 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.

  9. Enhanced 1G 4 emission in NaLaF 4: Pr 3+, Yb 3+ and charge transfer in NaLaF 4: Ce 3+, Yb 3+ studied by fourier transform luminescence spectroscopy

    NASA Astrophysics Data System (ADS)

    van der Kolk, E.; Ten Kate, O. M.; Wiegman, J. W.; Biner, D.; Krämer, K. W.

    2011-05-01

    A high resolution luminescence study of NaLaF 4: 1%Pr 3+, 5%Yb 3+ and NaLaF 4: 1%Ce 3+, 5%Yb 3+ in the UV to NIR spectral range using a InGaAs detector and a fourier transform interferometer is reported. Although the Pr 3+( 3P 0 → 1G 4), Yb 3+( 2F 7/2 → 2F 5/2) energy transfer step takes place, significant Pr 3+1G 4 emission around 993, 1330 and 1850 nm is observed. No experimental proof for the second energy transfer step in the down-conversion process between Pr 3+ and Yb 3+ can be given. In the case of NaLaF 4: Ce 3+, Yb 3+ it is concluded that the observed Yb 3+ emission upon Ce 3+ 5d excitation is the result of a charge transfer process instead of down-conversion.

  10. Synthesis and anticonvulsant activity of 6-alkoxy-[1,2,4]triazolo[3,4-a]phthalazines.

    PubMed

    Zhang, Lei; Guan, Li-Ping; Sun, Xian-Yu; Wei, Cheng-Xi; Chai, Kyu-Yun; Quan, Zhe-Shan

    2009-03-01

    A new series of 6-alkoxy-[1,2,4]triazolo[3,4-a]phthalazines (3a-3v) were synthesized and their anticonvulsant activity and neurotoxicity were evaluated by the maximal electroshock test and the rotarod test respectively. Significant anticonvulsant activity was displayed by a number of compounds. The most promising compounds 6-(4-chlorobenzyloxy)-[1,2,4]triazolo[3,4-a]phthalazine (3f) and 6-heptyloxy-[1,2,4]triazolo[3,4-a]phthalazine (3s) showed a median effective dose of 7.1 and 11.0 mg/kg, and had protective index value of 5.2 and 8.0 respectively. The two compounds were further found to have potent activity against seizures induced by pentylenetetrazole, isoniazid, thiosemicarbazide, 3-mercaptopropionic acid but not seizures induced by strychnine, indicating that the two compounds might function by enhancing gamma-aminobutyric acid neurotransmission.

  11. 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)

  12. Poly[(μ3-hydrogenphosphato)(4H-1,2,4-triazole-κN 1)zinc

    PubMed Central

    Aitenneite, Hafid; El Bouari, Abdeslam; Sebti, Said; Saadi, Mohamed; El Ammari, Lahcen; Adil, Karim

    2012-01-01

    The asymmetric unit of the title compound, [Zn(HPO4)(C2H3N3)]n, contains one Zn2+ cation, one (HPO4)2− anion and a 1,2,4 triazole ligand. The Zn2+ cation is coordinated in a quite regular tetra­hedral geometry by O atoms from three phosphate groups and a tertiary N atom from the triazole ring. Each phosphate anion is connected to three ZnII cations, leading to a series of corrugated organic–inorganic layers parallel to the ac plane. The overall structure involves stacking of complex hybrid organic–inorganic layers along the b axis. Cohesion in the crystal is ensured by an infinite three-dimensional network of N—H⋯O and O—H⋯O hydrogen bonds between the phosphate groups and the triazole ligands. PMID:23284388

  13. Nitro group photoreduction of 4-(2-nitrophenyl)- and 4-(3-nitrophenyl)-1,4-dihydropyridines

    NASA Astrophysics Data System (ADS)

    Görner, Helmut

    2010-08-01

    The photoprocesses of nifedipine, a 4-(2-nitrophenyl)-1,4-dihydropyridine, and nimodipine and nitrendipine, two 3-nitrophenyl Hantzsch-type analogues, were studied by steady-state and time-resolved methods. The intramolecular photoreduction of nifedipine into its nitrosophenyl product takes place within a few ns. The quantum yield of conversion is Φred = 0.3 and does not depend significantly on the oxygen concentration and solvent properties. Formation of the fully reduced 4-(2-aminophenyl)-1,4-dihydropyridine as minor product is indicated by fluorescence spectroscopy. The photoreduction of nimodipine and nitrendipine is inefficient, Φred = 0.002 in acetonitrile, but markedly enhanced in the presence of donors such as triethylamine (TEA) and 2-propanol, e.g. for TEA Φred is up to 0.03. The triplet states of nimodipine and nitrendipine were characterized. They react intermolecularly with TEA and 2-propanol, forming radicals as intermediates and eventually several reduction products.

  14. The Cac1 subunit of histone chaperone CAF-1 organizes CAF-1-H3/H4 architecture and tetramerizes histones

    PubMed Central

    Liu, Wallace H; Roemer, Sarah C; Zhou, Yeyun; Shen, Zih-Jie; Dennehey, Briana K; Balsbaugh, Jeremy L; Liddle, Jennifer C; Nemkov, Travis; Ahn, Natalie G; Hansen, Kirk C; Tyler, Jessica K; Churchill, Mair EA

    2016-01-01

    The histone chaperone Chromatin Assembly Factor 1 (CAF-1) deposits tetrameric (H3/H4)2 histones onto newly-synthesized DNA during DNA replication. To understand the mechanism of the tri-subunit CAF-1 complex in this process, we investigated the protein-protein interactions within the CAF-1-H3/H4 architecture using biophysical and biochemical approaches. Hydrogen/deuterium exchange and chemical cross-linking coupled to mass spectrometry reveal interactions that are essential for CAF-1 function in budding yeast, and importantly indicate that the Cac1 subunit functions as a scaffold within the CAF-1-H3/H4 complex. Cac1 alone not only binds H3/H4 with high affinity, but also promotes histone tetramerization independent of the other subunits. Moreover, we identify a minimal region in the C-terminus of Cac1, including the structured winged helix domain and glutamate/aspartate-rich domain, which is sufficient to induce (H3/H4)2 tetramerization. These findings reveal a key role of Cac1 in histone tetramerization, providing a new model for CAF-1-H3/H4 architecture and function during eukaryotic replication. DOI: http://dx.doi.org/10.7554/eLife.18023.001 PMID:27690308

  15. (3R,4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl]chroman-4,7-diol: a conformationally restricted analogue of the NR2B subtype-selective NMDA antagonist (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)- 1-propanol.

    PubMed

    Butler, T W; Blake, J F; Bordner, J; Butler, P; Chenard, B L; Collins, M A; DeCosta, D; Ducat, M J; Eisenhard, M E; Menniti, F S; Pagnozzi, M J; Sands, S B; Segelstein, B E; Volberg, W; White, W F; Zhao, D

    1998-03-26

    (1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP-101,606, 1) is a recently described antagonist of N-methyl-D-aspartate (NMDA) receptors containing the NR2B subunit. In the present study, the optimal orientation of compounds of this structural type for their receptor was explored. Tethering of the pendent methyl group of 1 to the phenolic aromatic ring via an oxygen atom prevents rotation about the central portion of the molecule. Several of the new chromanol compounds have high affinity for the racemic [3H]CP-101,606 binding site on the NMDA receptor and protect against glutamate toxicity in cultured hippocampal neurons. The new ring caused a change in the stereochemical preference of the receptor-cis (erythro) compounds had better affinity for the receptor than the trans isomers. Computational studies suggest that steric interactions between the pendent methyl group and the phenol ring in the acyclic series determine which structures can best fit the receptor. The chromanol analogue, (3R,4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1- yl]chroman-4,7-diol (12a, CP-283,097), was found to possess potency and selectivity comparable to CP-101,606. Thus 12a is a new tool to explore the function of the NR2B-containing NMDA receptors.

  16. Synthesis, crystal structure, experimental and theoretical investigations of 3-(4-ethoxy-3-methoxyphenyl)-1-phenylprop-2-en-1-one

    NASA Astrophysics Data System (ADS)

    Anam, Faiza; Abbas, Asghar; Lo, Kong Mun; Hameed, Shahid; Ramasami, Ponnadurai; Umar, Yunusa; Ullah, Aman; Naseer, Muhammad Moazzam

    2017-01-01

    A chalcone derivative namely, (E)-3-(4-ethoxy-3-methoxyphenyl)-1-phenylprop-2-en-1-one (1v) has been synthesized and characterized on the basis of its spectral data. The solid state self-assembly studies of 1v were carried out through single crystal X-ray technique to see the major non-covalent interactions responsible for molecular alignment in the solid state. Furthermore, the optimized molecular geometry, vibrational frequencies, 1H and 13C NMR chemical shift (in gas and in chloroform solvent) values and the molecular electrostatic potential (MEP) surface parameters of 1v were calculated using DFT/B3LYP/HF/M06 method with 6-311++G (d,p) basis set in ground state. All the theoretical calculations for 1v were found in good agreement with experimental data.

  17. Novel aryl and heteroaryl substituted N-[3-(4-phenylpiperazin-1-yl)propyl]-1,2,4-oxadiazole-5-carboxamides as selective GSK-3 inhibitors.

    PubMed

    Koryakova, Angela G; Ivanenkov, Yan A; Ryzhova, Elena A; Bulanova, Elena A; Karapetian, Ruben N; Mikitas, Olga V; Katrukha, Eugeny A; Kazey, Vasily I; Okun, Ilya; Kravchenko, Dmitry V; Lavrovsky, Yan V; Korzinov, Oleg M; Ivachtchenko, Alexandre V

    2008-06-15

    Synthesis, biological evaluation, and SAR dependencies for a series of novel aryl and heteroaryl substituted N-[3-(4-phenylpiperazin-1-yl)propyl]-1,2,4-oxadiazole-5-carboxamide inhibitors of GSK-3beta kinase are described. The inhibitory activity of the synthesized compounds is highly dependent on the character of substituents in the phenyl ring and the nature of terminal heterocyclic fragment of the core molecular scaffold. The most potent compounds from this series contain 3,4-di-methyl or 2-methoxy substituents within the phenyl ring and 3-pyridine fragment connected to the 1,2,4-oxadiazole heterocycle. These compounds selectively inhibit GSK-3beta kinase with IC(50) value of 0.35 and 0.41 microM, respectively.

  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. Evidence for new bands in the 3nu1 and 4nu1 regions of propyne.

    PubMed

    Ganot, Yuval; Rosenwaks, Salman; Bar, Ilana

    2005-06-22

    Vibrationally mediated photodissociation and room-temperature photoacoustic (PA) spectroscopy have been used for obtaining action (monitoring the yield of H photofragments) and absorption spectra of the second (3nu(1)) and third (4nu(1)) C-H acetylenic stretches overtone regions in propyne. The band contours appearing in these regions seem mostly regular even though they are perturbed, as expressed by the origin shifts in different K components, splitting of the K structure, and splitting due to resonances between neighboring states. Symmetric rotor simulations of the band contours of the PA and action spectra allowed extraction of the molecular parameters and rough estimates for the homogeneous broadening arising from energy flow to the bath vibrational states. We particularly benefited from the reduced congestion in the jet-cooled action spectra and their simulations, which enabled observation of yet unknown features in the vicinity of the 3nu(1) and 4nu(1) states. Particularly, the emergence of the new state in the 3nu(1) region was confirmed by the action spectra monitored at several differing jet temperatures, suggesting that it is a dark state in IR vibrational excitation that becomes brighter in UV excitation to the upper electronic state. The monitored and Gaussian-fitted Doppler profiles point to the release of H photofragments with low average translational energies, attributed to an indirect dissociation process occurring after internal conversion to the ground electronic state and isomerization to allene.

  1. 1,3,5-Tri- and 1,3,4,5-tetra-substituted 1,4-diazepin-2-one solid-phase synthesis.

    PubMed

    Iden, Hassan S; Lubell, William D

    2008-01-01

    Solid-phase syntheses of 1,3,5-tri-substituted and 1,3,4,5-tetra-substituted 1,4-diazepin-2-ones 15-18 have been accomplished by employing inexpensive commercially available alpha- and beta-amino acids on Wang resin. Reductive amination of the imine formed by condensation of Wang aldehyde resin respectively with beta-alaninate 2 and beta-homophenylalaninate 3, followed by aminoacylation with a set of alpha-N-Boc amino acids (Phe epsilon-( Z)-Lys, and Leu) gave tertiary amide resins 7 and 8. Exposure of resins 7 and 8 to an excess of vinyl magnesium bromide in the presence of copper cyanide gave the corresponding gamma,delta-unsaturated ketone resins 9 and 10 by way of a cascade addition. Diazepinones were made by Boc deprotection and intramolecular reductive amination. To diversify the heterocycle, N-alkylation was performed using a series of alkyl halides. Alternatively, diazepinones 15e-g were obtained from treatment of methyl beta-alaninate resins 4 and 20 under similar copper-catalyzed cascade conditions to afford the gamma,delta-unsaturated ketone 21, which was acylated using alpha-N-Fmoc-amino acids (Phe, Trp, gamma-(t-Bu)-Glu). Formation of diazepinones 15 followed a similar protocol, after Fmoc removal with piperidine. Cleavage of the heterocycles with TFA/TES 95:5 gave the N1-p-hydroxybenzyl diazepinones 15-18 in overall isolated yields from 6 to 24% after purification in purities ranging from 81 to 100% according to LCMS analysis.

  2. Crystal structure and magnetic properties of Li,Cr-containing molybdates Li 3Cr(MoO 4) 3, LiCr(MoO 4) 2 and Li 1.8Cr 1.2(MoO 4) 3

    NASA Astrophysics Data System (ADS)

    Sarapulova, A.; Mikhailova, D.; Senyshyn, A.; Ehrenberg, H.

    2009-12-01

    Single crystals of LiCr(MoO 4) 2, Li 3Cr(MoO 4) 3 and Li 1.8Cr 1.2(MoO 4) 3 were grown by a flux method during the phase study of the Li 2MoO 4-Cr 2(MoO 4) 3 system at 1023 K. LiCr(MoO 4) 2 and Li 3Cr(MoO 4) 3 single phases were synthesized by solid-state reactions. Li 3Cr(MoO 4) 3 adopts the same structure type as Li 3In(MoO 4) 3 despite the difference in ionic radii of Cr 3+ and In 3+ for octahedral coordination. Li 3Cr(MoO 4) 3 is paramagnetic down to 7 K and shows a weak ferromagnetic component below this temperature. LiCr(MoO 4) 2 is isostructural with LiAl(MoO 4) 2 and orders antiferromagnetically below 20 K. The magnetic structure of LiCr(MoO 4) 2 was determined from low-temperature neutron diffraction and is based on the propagation vektor k⇒=({1}/{2},{1}/{2},0). The ordered magnetic moments were refined to 2.3(1) μ B per Cr-ion with an easy axis close to the [1 1 1¯] direction. A magnetic moment of 4.37(3) μ B per Cr-ion was calculated from the Curie constant for the paramagnetic region. The crystal structures of the hitherto unknown Li 1.8Cr 1.2(MoO 4) 3 and LiCr(MoO 4) 2 are compared and reveal a high degree of similarity: In both structures MoO 4-tetrahedra are isolated from each other and connected with CrO 6 and LiO 5 via corners. In both modifications there are Cr 2O 10 fragments of edge-sharing CrO 6-octahedra.

  3. 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…

  4. (Z)-5-(3,4,5-Tri-meth-oxy-styr-yl)-2,3-di-hydro-thieno[3,4-b][1,4]dioxine.

    PubMed

    Liu, Yu-Tao; Chu, Gang

    2014-04-01

    In the title compound, C17H18O5S, an analogue of the potent anti-cancer agent combretastatin A-4, the alkene C=C bond has a cis conformation and the C-C=C-C torsion angle is 9.0 (3)°. The dihedral angle between the benzene and thio-phene rings is 54.07 (4)°. The dioxene ring adopts a half-chair conformation, with the C atoms of the methyl-ene groups displaced by -0.325 (2) and 0.341 (3) Å from the plane of the other atoms. The C atoms of the two meta-meth-oxy groups are close to being coplanar with their attached benzene ring [displacements = -0.025 (2) and -0.196 (2) Å], whereas the C atom of the para-meth-oxy group is significantly displaced [by -1.107 (2) Å]. In the crystal, C-H⋯O hydrogen bonds link the mol-ecules into [0-11] chains, which feature two different types of R 2 (2)(6) loops.

  5. Spectroscopic properties and photochemistry of [Fe(CO) 3(1,4-Diazabuta-1,3-diene)] complexes

    NASA Astrophysics Data System (ADS)

    Stufkens, D. J.; Kokkes, M. W.; Oskam, A.

    1984-03-01

    Different photochemical reactions are found for [Fe(CO) 3(dab)] (dab = 1,4-diazabuta-1,3-diene) in matrices at 10 K and in solutions at room temperature. Matrix photolysis results in loss of CO via an intermediate in which the dab-ligand is π,π-coordinated to the metal, whereas photolysis in solution leads to CO-substitution after breaking of a metal-nitrogen bond. This behaviour is discussed in relationship to the spectroscopic properties of [Fe(CO) 3(dab)].

  6. Synthesis and Biological Evaluation of Some Novel 5-[(3-Aralkyl Amido/Imidoalkyl) Phenyl]-1,2,4-Triazolo[3,4-b]-1,3,4-Thiadiazines as Antiviral Agents

    PubMed Central

    Pandey, Vinod Kumar; Tusi, Zehra; Tusi, Sumerah; Joshi, Madhawanand

    2012-01-01

    A series of novel 4-amino-5-mercapto-3-[(3-aralkyl amido/imidoalkyl) phenyl]-1,2,4-triazoles (5a-d) were obtained by treating m-(aralkyl amido/imidoalkyl) benzoic acid hydrazides (3a-d) with carbon disulphide in alcoholic KOH and hydrazine hydrate, respectively. These triazole derivatives were employed in the synthesis of 5-[(3′-aralkyl amido/imidoalkyl) phenyl]-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (6a-d). The newly synthesized compounds were evaluated for their antiviral activity against two animal viruses, namely, Japanese encephalitis virus (JEV) strain P20778 and herpes simplex virus-1 (HSV-1) strain 753166. PMID:24052850

  7. 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.

  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. An efficient synthesis of 3,4-Dihydrofuro [3,4-B] [1,4] dioxepine-6,8-dicarboxylic Acid

    NASA Astrophysics Data System (ADS)

    DENG, D. D.; WANG, L. P.; YAN, H. W.; SUN, X. X.; WANG, Z.

    2017-01-01

    As a class of important conjugated polymers, electroluminescent material of polyfuran possess a lot of merits, including good stability, structure is easy to be modified and controllable electrochemical properties. This study uses ethylene diglycol, diethyl oxalate, 1,3- dibromopropane and so on as raw materials to synthesize 3, 4 - ethylenedioxy furan monomer and similar derivatives via oxidation, acetylation, hydrolysis and elimination reaction, etc.

  10. Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor.

    PubMed

    Vandurm, Pierre; Cauvin, Christine; Guiguen, Allan; Georges, Benoît; Le Van, Kiet; Martinelli, Valérie; Cardona, Christelle; Mbemba, Gladys; Mouscadet, Jean-François; Hevesi, László; Van Lint, Carine; Wouters, Johan

    2009-08-15

    Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30 degrees ). Docking studies suggest binding modes in agreement with structure-activity relationships.

  11. 49 CFR 173.124 - Class 4, Divisions 4.1, 4.2 and 4.3-Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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 decomposition... decomposition temperature is 50 °C (122 °F) or higher for a 50 kg (110 pounds) package). A...

  12. 49 CFR 173.124 - Class 4, Divisions 4.1, 4.2 and 4.3-Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 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 decomposition... decomposition temperature is 50 °C (122 °F) or higher for a 50 kg (110 pounds) package). A...

  13. 49 CFR 173.124 - Class 4, Divisions 4.1, 4.2 and 4.3-Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 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 decomposition... decomposition temperature is 50 °C (122 °F) or higher for a 50 kg (110 pounds) package). A...

  14. 49 CFR 173.124 - Class 4, Divisions 4.1, 4.2 and 4.3-Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 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 decomposition... decomposition temperature is 50 °C (122 °F) or higher for a 50 kg (110 pounds) package). A...

  15. 49 CFR 173.124 - Class 4, Divisions 4.1, 4.2 and 4.3-Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 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 decomposition... decomposition temperature is 50 °C (122 °F) or higher for a 50 kg (110 pounds) package). A...

  16. 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…

  17. A π-stacked chain of hydrogen-bonded dimers in 3-tert-butyl-1-(4-chlorophenyl)-4-phenylindeno[1,2-b]pyrazolo[4,3-e]pyridin-5(1H)-one and a π-stacked sheet of hydrogen-bonded chains in 3-tert-butyl-1-(4-chlorophenyl)-4-(4-methoxyphenyl)indeno[1,2-b]pyrazolo[4,3-e]pyridin-5(1H)-one.

    PubMed

    Portilla, Jaime; Lizarazo, Carolina; Cobo, Justo; Glidewell, Christopher

    2011-12-01

    In 3-tert-butyl-1-(4-chlorophenyl)-4-phenylindeno[1,2-b]pyrazolo[4,3-e]pyridin-5(1H)-one, C(29)H(22)ClN(3)O, (I), inversion-related pairs of molecules are linked by C-H...O hydrogen bonds to form R(2)(2)(18) dimers, which are themselves linked into a chain by a π-π stacking interaction between inversion-related pairs of molecules. In 3-tert-butyl-1-(4-chlorophenyl)-4-(4-methoxyphenyl)indeno[1,2-b]pyrazolo[4,3-e]pyridin-5(1H)-one, C(30)H(24)ClN(3)O(2), (II), which crystallizes in the space group P-1, with Z' = 2 and with different orientations for the methoxy groups in the two independent molecules, a combination of C-H···O and C-H···π(arene) hydrogen bonds links the molecules into chains of rings, which are further linked into sheets by a π-π stacking interaction.

  18. 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.

  19. Energetic Materials Based on 5,5'-Diamino-4,4'-dinitramino-3,3'-bi-1,2,4-triazole.

    PubMed

    Klapötke, Thomas M; Leroux, Marcel; Schmid, Philipp C; Stierstorfer, Jörg

    2016-03-18

    A simple and straightforward synthesis of 5,5'-diamino-4,4'-dinitramino-3,3'-bi-1,2,4-triazole by the selective nitration of 4,4',5,5'-tetraamino-3,3'-bi-1,2,4-triazole is presented. The interaction of the amino and nitramino groups improves the energetic properties of this functionalized bitriazole. For a deeper investigation of these properties, various nitrogen-rich derivatives were synthesized. The new compounds were investigated and characterized by spectroscopy ((1)H and (13)C NMR, IR, Raman), elemental analysis, mass spectrometry, differential thermal analysis (DTA), X-ray analysis, and impact and friction sensitivities (IS, FS). X-ray analyses were performed and deliver insight into structural characteristics with which the stability of the compounds can be explained. The standard enthalpies of formation were calculated for all compounds at the CBS-4M level of theory, revealing highly positive heats of formation. The energetic performance of the new molecules was predicted with the EXPLO5 V6.02 computer. A small-scale shock reactivity test (SSRT) and a toxicity test gave a first impression of the performance and toxicity of selective compounds.

  20. 3-Hydroxy-4-pyrones as Precursors of 4-Methoxy-3-oxidopyridinium Ylides. An Expeditious Entry to Highly Substituted 8-Azabicyclo[3.2.1]octanes.

    PubMed

    Rumbo, Antonio; Mouriño, Antonio; Castedo, Luis; Mascareñas, José L.

    1996-09-06

    3-Hydroxy-4-pyridones, which are easily prepared from commercially available 3-hydroxy-4-pyrones, can be readily transformed into 4-methoxy-3-oxidopyridinium ylides by treatment with methyl trifluoromethanesulfonate and subsequent deprotonation with a non-nucleophilic base. These ylides are capable of undergoing cycloaddition to several electron-deficient alkenes, thus allowing the synthesis of highly functionalized azabicyclo[3.2.1]octane moieties. The rich substitution patterns of these frameworks might allow their divergent conversion to a variety of natural and non-natural tropane alkaloids.

  1. 40 CFR 721.1450 - 1,3-Benzenediamine, 4-(1,1-di-methylethyl)-ar-methyl.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-methylethyl)-ar-methyl. 721.1450 Section 721.1450 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1450 1,3-Benzenediamine, 4-(1,1-di-methylethyl)-ar-methyl. (a) Chemical...-dimethylethyl)-ar-methyl. (2) The significant new uses are: (i) Use other than for applications where...

  2. 40 CFR 721.1450 - 1,3-Benzenediamine, 4-(1,1-di-methylethyl)-ar-methyl.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-methylethyl)-ar-methyl. 721.1450 Section 721.1450 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1450 1,3-Benzenediamine, 4-(1,1-di-methylethyl)-ar-methyl. (a) Chemical...-dimethylethyl)-ar-methyl. (2) The significant new uses are: (i) Use other than for applications where...

  3. 40 CFR 721.1450 - 1,3-Benzenediamine, 4-(1,1-di-methylethyl)-ar-methyl.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-methylethyl)-ar-methyl. 721.1450 Section 721.1450 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1450 1,3-Benzenediamine, 4-(1,1-di-methylethyl)-ar-methyl. (a) Chemical...-dimethylethyl)-ar-methyl. (2) The significant new uses are: (i) Use other than for applications where...

  4. 40 CFR 721.1450 - 1,3-Benzenediamine, 4-(1,1-di-methylethyl)-ar-methyl.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-methylethyl)-ar-methyl. 721.1450 Section 721.1450 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1450 1,3-Benzenediamine, 4-(1,1-di-methylethyl)-ar-methyl. (a) Chemical...-dimethylethyl)-ar-methyl. (2) The significant new uses are: (i) Use other than for applications where...

  5. IR, FT-ICR-MS studies on (1'S, 6'S)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0] non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride salt.

    PubMed

    Lin, Zhiwei

    2014-01-01

    The infrared spectra of (1'S, 6'S)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0] non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride salt (CLF-HCl) were studied and compared with free base. Their fragmentation pathways were investigated using tandem mass spectrometric (MS/MS) techniques on Fourier-transform ion cyclotron resonance spectrum, and many characteristic fragment ions were found.

  6. A computational study of simultaneous cation/anion interactions in model clusters containing all-cis 1,2,3-trifluorocyclopropane (F3C3H3) and all-cis 1,2,3,4-tetrafluorobutane (F4C4H4)

    NASA Astrophysics Data System (ADS)

    McDowell, Sean A. C.

    2016-11-01

    A computational study of two model clusters involving the all-cis 1,2,3-trifluorocyclopropane (F3C3H3) and the all-cis 1,2,3,4-tetrafluorocyclobutane (F4C4H4) molecules was undertaken. These clusters involve the simultaneous attachment of a cation (Li+/Na+) to the "negative" face of F3C3H3/F4C4H4 (via interaction with the Csbnd F bonds) and a model F- anion to the "positive" face of F3C3H3/F4C4H4 (via the adjacent Csbnd H bonds). The relative stabilities of the two model clusters was investigated and extended to the neutral M+sbnd F4C4H4sbnd X- (M = Li, Na, K; X = F, Cl, Br) clusters. The cation-anion electrostatic interaction is the main source of attraction in these highly polar moieties.

  7. One-pot synthesis of novel 1H-pyrimido[4,5-c][1,2]diazepines and pyrazolo[3,4-d]pyrimidines

    PubMed Central

    Prajapati, Dipak; Baruah, Partha P; Gogoi, Baikuntha J; Sandhu, Jagir S

    2006-01-01

    Novel 1H-pyrimido [4,5-c][1,2]diazepines 3 & 4 and pyrazolo [3,4-d]pyrimidines 6 were regioselectively synthesised by the reaction of 1,3-dimethyl-6-hydrazinouracils 1 with various α,β-unsaturated compounds 2 and α-ketoalkynes 8 in excellent yields. PMID:16556308

  8. 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-...

  9. 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-...

  10. Crystal structure of rac-2,3-diphenyl-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one 1-oxide

    PubMed Central

    Yennawar, Hemant P.; Yang, Ziwei; Silverberg, Lee J.

    2016-01-01

    In the title compound, C16H15NO2S [alternative name: rac-2,3-diphenyl-1,3-thia­zinan-4-one 1-oxide], the thia­zine ring exhibits an envelope conformation, with the S atom forming the flap. The sulfoxide O atom is in a pseudo-axial position on the thia­zine ring and is trans to the phenyl group on C-2. The phenyl rings form a dihedral angle of 89.47 (19)°. In this racemate crystal, homochiral mol­ecules form slabs parallel to (010) of thickness b/2 which then stack with alternating chirality in the b-axis direction. The stacking is aided by edge-to-face inter­actions between the phenyl rings of racemic mol­ecules. Within each of the single-enanti­omer slabs, the mol­ecules are held by C—H⋯O-type inter­actions, with an H⋯O distance of 2.30 Å, forming infinite chains along the c-axis direction, as well by the edge-to-face inter­actions between phenyl rings of neighboring mol­ecules in the a-axis direction. PMID:27840703

  11. Reactivity study of 1H-thieno[3,2-d][1,3]oxazine-2,4-dione toward the synthesis of bicyclic 3,4-dihydro-1H-thieno[3,2-e][1,4]diazepine-2,5-dione analogues.

    PubMed

    Brouillette, Yann; Lisowski, Vincent; Fulcrand, Pierre; Martinez, Jean

    2007-03-30

    A series of 10 optically pure 3,4-dihydro-1H-thieno[3,2-e][1,4]diazepine-2,5-dione derivatives has been synthesized in 41-75% yields on treatment of 1H-thieno[3,2-d][1,3]oxazine-2,4-dione with different natural alpha-amino acids.

  12. Synthesis and metabolic studies of 1α,2α,25-, 1α,4α,25- and 1α,4β,25-trihydroxyvitamin D3.

    PubMed

    Takano, Masashi; Sawada, Daisuke; Yasuda, Kaori; Nishikawa, Miyu; Takeuchi, Akiko; Takagi, Ken-Ichiro; Horie, Kyohei; Reddy, G Satyanarayana; Chen, Tai C; Sakaki, Toshiyuki; Kittaka, Atsushi

    2015-04-01

    Three different A-ring perhydroxylated trihydroxyvitamin D3 metabolites were synthesized from their appropriate A-ring precursors and CD-ring for their potential therapeutic applications. We first chemically synthesized 1α,2α,25-trihydroxyvitamin D3 [1α,2α,25(OH)3D3] to study its VDR binding affinity because this metabolite is a product of recombinant human CYP3A4 catalysis when 2α-(3-hydroxypropoxy)-1α,25-dihydroxyvitamin D3 (O2C3), a more potent vitamin D receptor (VDR) binder than 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], is used as the substrate. We found that this metabolite retained 27.3% of the VDR binding affinity compared to 1α,25(OH)2D3. The kcat/Km value of CYP24A1 for 1α,2α,25(OH)3D3 is 60% of that for 1α,25(OH)2D3. Since the biological activity and the metabolic fate of a naturally occurring C4-hydroxylated vitamin D2 metabolite found in the serum of rats treated with pharmacological doses of vitamin D2 have never been described, we next synthesized 1α,4α,25-trihydroxyvitamin D3 and its diastereoisomer, 1α,4β,25-trihydroxyvitamin D3, to study their metabolism and biological activities. Both 4-hydroxylated isomers showed weaker VDR binding affinity than 1α,25(OH)2D3. Although either 4-hydroxylated isomer can be metabolized by CYP24A1 almost at the same level as 1α,25(OH)2D3, their metabolic patterns catalyzed by uridine 5'-diphosphoglucuronosyltransferase (UGT) are different; only the 4α-hydroxylated analog can be metabolized by UGT to produce a glucuronate conjugate. The results provide important information for the synthesis of new novel chemotherapeutic vitamin D analogs which would be less subjective to degradation and therefore more bioavailable than 1α,25(OH)2D3. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

  13. Evaluation of 3,3′,4′-trihydroxyflavone and 3,6,4′-trihydroxyflavone (4′-O-glucuronidation) as the in vitro functional markers for hepatic UGT1A1

    PubMed Central

    Wu, Baojian; Zhang, Shuxing; Hu, Ming

    2012-01-01

    Identifying UDP-glucuronosyltransferase (UGT)-selective probes (substrates that are primarily glucuronidated by a single isoform) is complicated by the enzymes' large overlapping substrate specificity. Here, regioselective glucuronidation of two flavonoids 3,3′,4′-trihydroxyflavone (33′4′THF) and 3,6,4′-trihydroxyflavone (364′THF) is used to probe the activities of hepatic UGT1A1. The glucuronidation kinetics of 33′4′THF and 364′THF was determined using 12 recombinant human UGT isoforms and pooled human liver microsomes (pHLM). The individual contribution of main UGT isoforms to the metabolism of the two flavonoids in pHLM was estimated using the relative activity factor approach. UGT1A1 activity correlation analyses using flavonoids-4′-O-glucuronidation vs. β-estradiol-3-glucuronidation (a well-recognized marker for UGT1A1) or vs. SN-38 glucuronidation were performed using a bank of HLMs (n=12) including three UGT1A1-genotyped HLMs (i.e., UGT1A1*1*1, UGT1A1*1*28 and UGT1A1*28*28). The results showed that UGT1A1 and 1A9, followed by 1A7, were the main isoforms for glucuronidating the two flavonoids, where UGT1A1 accounted for 92 ± 7 % and 91 ± 10 % of 4′-O-glucuronidation of 33′4′THF and 364′THF, respectively, and UGT1A9 accounted for most of the 3-O-glucuronidation. Highly significant correlations (R2 > 0.944, p < 0.0001) between the rates of flavonoids 4′-O-glucuronidation and that of estradiol-3-glucuronidation or SN-38 glucuronidation were observed across 12 HLMs. In conclusion, UGT1A1-mediated 4′-O-glucuronidation of 33′4′THF and 364′THF were highly correlated with glucuronidation of estradiol (3-OH) and SN-38. This study demonstrated for the first time that regioselective glucuronidation of flavonoids can be applied to probe hepatic UGT1A1 activity in vitro. PMID:21985641

  14. Crystal structure of [propane-1,3-diylbis(piperidine-4,1-di-yl)]bis-[(pyridin-4-yl)methanone]-isophthalic acid (1/1).

    PubMed

    Murray, Nathan H; Biros, Shannon M; LaDuca, Robert L

    2014-11-01

    In the crystal structure of the title co-crystal, C25H32N4O2·C8H6O4, isophthalic acid and [propane-1,3-diylbis(piperidine-4,1-di-yl)]bis-(pyridin-4-yl-methanone) mol-ecules are connected into supra-molecular chains aligned along the c axis by O-H⋯N hydrogen bonding. These aggregate into supra-molecular layers oriented parallel to the ac plane by C-H⋯O inter-actions. These layers then stack in an ABCD pattern along the b-axis direction by additional C-H⋯O inter-actions to give the full three-dimensional crystal structure. The central chain in the di-pyridyl-amide molecule has an anti-gauche conformation.

  15. Regulation of histamine- and UTP-induced increases in Ins(1,4,5)P3, Ins (1,3,4,5)P4 and Ca2+ by cyclic AMP in DDT1 MF-2 cells.

    PubMed

    Sipma, H; Duin, M; Hoiting, B; den Hertog, A; Nelemans, A

    1995-01-01

    1. Stimulation of P2U-purinoceptors with UTP or histamine H1-receptors with histamine gave rise to the formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) in DDT1 MF-2 smooth muscle cells. 2. Stimulation of P2U-purinoceptors or histamine H1-receptors caused an increase in cytoplasmic Ca2+, consisting of an initial peak, representing the release of Ca2+ from internal stores and a sustained phase representing Ca2+ influx. 3. The P2U-purinoceptor-mediated Ca(2+)-entry mechanism was more sensitive to UTP than Ca(2+)-mobilization (EC50: 3.3 microM +/- 0.4 microM vs 55.1 microM +/- 9.2 microM), in contrast to these processes activated by histamine H1-receptors (EC50: 5.8 microM +/- 0.6 microM vs 3.1 microM +/- 0.5 microM). 4. Pre-stimulation of cells with several adenosine 3':5'-cyclic monophosphate (cyclic AMP) elevating agents, reduced the histamine H1-receptor-mediated formation of Ins(1,4,5)P3 and Ins(1,3,4,5)P4. Forskolin completely inhibited Ins(1,4,5)P3 formation (IC50: 158 +/- 24 nM) whereas Ins(1,3,4,5)P4 formation was inhibited by only 45% (IC50: 173 +/- 16 nM). The P2U-purinoceptor-mediated production of these inositol phosphates was not affected by cyclic AMP. 5. Forskolin and isoprenaline reduced the histamine-induced increase in cytoplasmic Ca2+, as measured in Ca2+ containing medium and in nominally Ca(2+)-free medium but did not change the UTP-induced increase in cytoplasmic Ca2+. 6. These results clearly demonstrate that cyclic AMP differentially regulates components of the histamine induced phospholipase C signal transduction pathway. Furthermore, cyclic AMP does not affect the phospholipase C pathway activated by stimulation of P2U-purinoceptors in DDT1 MF-2 cells.

  16. 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.

  17. Psh1 is an E3 ubiquitin ligase that targets the centromeric histone variant Cse4

    PubMed Central

    Hewawasam, Geetha; Shivaraju, Manjunatha; Mattingly, Mark; Venkatesh, Swaminathan; Martin-Brown, Skylar; Florens, Laurence; Workman, Jerry L.; Gerton, Jennifer L.

    2010-01-01

    Cse4 is a variant of histone H3 that is incorporated into a single nucleosome at each centromere in budding yeast. We have discovered an E3 ubiquitin ligase, called Psh1, which controls the cellular level of Cse4 via ubiquitylation and proteolysis. The activity of Psh1 is dependent on both its RING and Zinc finger domains. We demonstrate the specificity of the ubiquitylation activity of Psh1 toward Cse4 in vitro and map the sites of ubiquitylation. Mutation of key lysines prevents ubiquitylation of Cse4 by Psh1 in vitro and stabilizes Cse4 in vivo. While deletion of Psh1 stabilizes Cse4, elimination of the Cse4-specific chaperone Scm3 destabilizes Cse4 and the addition of Scm3 to the Psh1-Cse4 ubiquitylation reaction prevents Cse4 ubiquitylation, together suggesting Scm3 may protect Cse4 from ubiquitylation. Without Psh1, Cse4 overexpression is toxic and Cse4 is found at ectopic locations. Our results suggest Psh1 functions to prevent the mislocalization of Cse4. PMID:21070970

  18. 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

  19. 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.

  20. 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

  1. 3-Acetyl-2-methyl-4-(pyridin-3-yl)-1,4-di­hydro­indeno­[1,2-b]pyridin-5-one

    PubMed Central

    Bisenieks, Imants; Mishnev, Anatoly; Bruvere, Imanta; Vigante, Brigita; Andzans, Zigmars

    2013-01-01

    In the title compound, C20H16N2O2, the condensed tricyclic fragment is near to planar, with an r.m.s. deviation of 0.0531 Å. The 1,4-di­hydro­pyridine (1,4-DHP) ring adopts a slightly puckered boat-like conformation. The N and opposite C atoms deviate from the least-squares plane of the four other ring atoms by 0.039 (3) and 0.141 (3) Å, respectively. The C=O group located at the tricyclic fragment is fixed in an s-trans orientation, while the second C=O group adopts an s-cis orientation with respect to the double bonds of the 1,4-DHP ring. The pyridine ring has a pseudo-axial orientation with respect to the 1,4-DHP ring. The dihedral angle between the tricyclic system and the pyridine ring is 77.3 (3)°. In the crystal, the pyridine N atom accepts a hydrogen bond from the N—H group of the 1,4-DHP ring. The hydrogen bonds link the mol­ecules into infinite C(8) chains along the b-axis direction. PMID:23723870

  2. 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.

  3. 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.

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false 1,2-Propanediol, 3-(2-propenyloxy... Substances § 721.1637 1,2-Propanediol, 3-(2-propenyloxy)-, bis(4-methylbenzene sulfonate); 2-propanol, 1- oxy.... (1) The chemical substances 1,2-propanediol, 3-(2-propenyloxy)-, bis(4-methylbenzenesulfonate) (PMN...

  5. 40 CFR 721.1637 - 1,2-Propanediol, 3-(2-propenyloxy)-, bis(4-methylbenzene sulfonate); 2-propanol, 1-[2-[[(4...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 1,2-Propanediol, 3-(2-propenyloxy... Substances § 721.1637 1,2-Propanediol, 3-(2-propenyloxy)-, bis(4-methylbenzene sulfonate); 2-propanol, 1- oxy.... (1) The chemical substances 1,2-propanediol, 3-(2-propenyloxy)-, bis(4-methylbenzenesulfonate) (PMN...

  6. 40 CFR 721.1637 - 1,2-Propanediol, 3-(2-propenyloxy)-, bis(4-methylbenzene sulfonate); 2-propanol, 1-[2-[[(4...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 1,2-Propanediol, 3-(2-propenyloxy)-, bis(4-methylbenzene sulfonate); 2-propanol, 1- oxy]ethoxy]-3-(2-propenyloxy)-4-methylbenzenesulfonate; and 2-propanol, 1- oxy] ethoxy]ethoxy]-3-(2-propenyloxy)-, 4-methylbenzenesulfonate. 721.1637 Section 721.1637 Protection of...

  7. 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...

  8. 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...-, 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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

    2016-08-31

    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.

  13. Ethyl methyl 1,4-dihydro-4-(3-nitrophenyl)-2, 6-bis(1-piperidylmethyl)pyridine-3,5-dicarboxylate.

    PubMed

    Duque, J; Novoa De Armas, H; Pomés Hernández, R; Suárez Navarro, M; Ochoa Rodríguez, E; Salfrán, E; Verdecia Reyes, Y; Blaton, N M; Peeters, O M; De Ranter, C J

    2000-11-01

    In the title compound, C(28)H(38)N(4)O(6), the 4-aryl substituent occupies a pseudo-axial position approximately orthogonal to the plane of the dihydropyridine ring [88.1 (3) degrees ]. The dihydropyridine ring adopts a flattened boat conformation. The H atom on the pyridine N atom is involved in a bifurcated intramolecular hydrogen bond, the acceptors being the N atoms of the two piperidylmethyl groups [N.N 2.629 (4) and 2.695 (4) A].

  14. 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.

  15. (3R,4S)-3,4-Isopropyl­idenedioxy-3,4-dihydro-2H-pyrrole 1-oxide

    PubMed Central

    Flores, Mari Fe; Garcia, Pilar; M. Garrido, Narciso; Sanz, Francisca; Diez, David

    2011-01-01

    The title compound C7H11NO3 was prepared by intra­molecular nucleophilic displacement of 2,3-O-iso-propyl­idene-d-erythronolactol. There are two mol­ecules in the asymmetric unit, which are related by a pseudo-inversion centre. The crystal structure determination confirms unequivocally the configuration of the chiral centres as 3S,4R. In the crystal structure, inter­molecular C—H⋯O inter­actions link the mol­ecules (into infinite zigzag chains along the a axis. PMID:21754432

  16. Characterization of a New Organic-Cation Cyclotetraphosphate: (1,4-HOC 6H 4NH 3) 4P 4O 12· 6H 2O

    NASA Astrophysics Data System (ADS)

    Soumhi, E. H.; Saadoune, I.; Driss, A.; Jouini, T.

    1999-05-01

    The tetra(para-phenolammonium)cyclotetraphosphate hexahydrate, (1,4-HOC6H4NH3)4P4O12· 6H2O (M=864.51 g mol-1), is monoclinicP21/cwith the unit cell parametersa=9.836(2) Å,b=8.591(1) Å,c:22.769(5) Å,β=95.41(2)°. The structure of this compound can be described as a succession of inorganic and organic sheets parallel to the (001) plane. The existence of the OH and NH3groups in positionparato the organic cation leads to the cohesion of the inorganic sheets, forming a three-dimensional network.The IR spectrum of (1,4-HOC6H4NH3)4P4O12· 6H2O is reported and discussed according to the theoretical group analysis. The IR data confirm the atomic arrangement within the structure. The coupled TG-DTA thermal study shows the successive departure of four and two water molecules, confirming the hydrated character of this cyclophosphate.

  17. Synthesis and antitumor activities of novel hybrid molecules containing 1,3,4-oxadiazole and 1,3,4-thiadiazole bearing Schiff base moiety.

    PubMed

    Zhang, Kai; Wang, Peng; Xuan, Li-Na; Fu, Xiao-Yun; Jing, Fen; Li, Sha; Liu, Yu-Ming; Chen, Bao-Quan

    2014-11-15

    A series of novel hybrid molecules containing 1,3,4-oxadiazole and 1,3,4-thiadiazole bearing Schiff base moiety were designed, synthesized and evaluated for their in vitro antitumor activities against SMMC-7721, MCF-7 and A549 human tumor cell lines by CCK-8 assay. The bioassay results demonstrated that most of the tested compounds showed potent antitumor activities, and some compounds exhibited stronger effects than positive control 5-fluorouracil (5-FU) against various cell lines. Among these compounds, compound 8d showed the best inhibitory effect against SMMC-7721 cells, with IC50 value of 2.84 μM. Compounds 8k and 8 n displayed highly effective antitumor activities against MCF-7 cells, with IC50 values of 4.56 and 4.25 μM, respectively. Compounds 8a and 8 n exhibited significant antiproliferative activity against A549 cells, with IC50 values of 4.11 and 4.13 μM, respectively. The pharmacological results suggest that the substituents of phenyl ring on the 1,3,4-oxadiazole are vital for modulating antiproliferative activities against various tumor cell lines.

  18. Synthesis, spectral characterization, single crystal and conformational study of 1,5-dimethyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-one derivatives

    NASA Astrophysics Data System (ADS)

    Venkateswaramoorthi, R.; John Francis Xavier, J.; Krishnasamy, K.; Saleem, H.

    2012-03-01

    1,5-Dimethyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-one 1 and their derivatives 2-8 were obtained by condensation of 2,6-dimethyl cyclohexanone, Ammonium acetate and substituted aromatic aldehydes and characterized by FT-IR, FT-Raman, 1H NMR, 13C NMR, GC-MS, HOMOCOSY, HSQC, NOESY, single crystal X-ray diffraction analysis and theoretical DFT calculation. Compound 1 crystallized in the Triclinic system, space group P-1 with a = 6.8950(5) Ǻ, b = 11.5889(9) Ǻ, c = 11.9172(9) Ǻ, α = 76.277(4)°, β = 78.000(3)°, γ = 72.920(4)°, V = 874.41(12) Ǻ3 and Z = 2. 1,5-Dimethyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-one 1 and their derivatives 2-8 were exist in boat-chair conformation with equatorial orientation of all the substituents at piperidine ring (two phenyl rings at C-2 and C-4 position, two methyl substituents at C-1 and C-5 position) of compound 1. In the crystal structure of compound 1, the molecules are connected by Nsbnd H⋯Odbnd C intermolecular hydrogen bonds. The existence of boat-chair conformation was confirmed by single crystal X-ray diffraction analysis and theoretical DFT calculation.

  19. Mitochondria targeted peptides protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity.

    PubMed

    Yang, Lichuan; Zhao, Kesheng; Calingasan, Noel Y; Luo, Guoxiong; Szeto, Hazel H; Beal, M Flint

    2009-09-01

    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.

  20. 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

  1. 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.

  2. Asymmetric radiation-induced inclusion polymerization of 3-methyl-1,4-pentadiene in deoxycholic acid

    NASA Astrophysics Data System (ADS)

    Cataldo, Franco; Ursini, Ornella; Angelini, Giancarlo

    2010-01-01

    The radiation-induced polymerization of 3-methyl-1,3-pentadiene (3MPD) as an inclusion complex in deoxycholic acid (DOCA) has produced in good yield the optically active polymer poly(3-methyl-1,4-pentadiene) (P3MPD) whose structure and properties were studied by FT-IR spectroscopy and thermal analysis (TGA, DTG and DTA). The data show that the polymer is essentially trans-1,4-P3MPD as expected for the polymerization in constrained media. Trans-1,4-P3MPD is optically active with [ α] D values comprised between +4.3 and +5.6. The optical rotatory dispersion curve of the P3MPD is completely different from that of DOCA as expected.

  3. Inositol 1,3,4,5-tetrakisphosphate and not phosphatidylinositol 3,4-bisphosphate is the probable precursor of inositol 1,3,4-trisphosphate in agonist-stimulated parotid gland.

    PubMed Central

    Downes, C P; Hawkins, P T; Irvine, R F

    1986-01-01

    When [3H]inositol-prelabelled rat parotid-gland slices were stimulated with carbachol, noradrenaline or Substance P, the major inositol trisphosphate produced with prolonged exposure to agonists was, in each case, inositol 1,3,4-trisphosphate. Much lower amounts of radioactivity were present in the inositol 1,4,5-trisphosphate fraction separated by anion-exchange h.p.l.c. Analysis of the inositol trisphosphate head group of phosphatidylinositol bisphosphate in [32P]Pi-labelled parotid glands showed the presence of phosphatidylinositol 4,5-bisphosphate, but no detectable phosphatidylinositol 3,4-bisphosphate. Carbachol-stimulated [3H]inositol-labelled parotid glands contained an inositol polyphosphate with the chromatographic properties and electrophoretic mobility of an inositol tetrakisphosphate, the probable structure of which was determined to be inositol 1,3,4,5-tetrakisphosphate. Since an enzyme in erythrocyte membranes is capable of degrading this tetrakisphosphate to inositol 1,3,4-trisphosphate, it is suggested to be the precursor of inositol 1,3,4-trisphosphate in parotid glands. PMID:2432882

  4. Synthesis and antitubercular activity of novel 4-substituted imidazolyl-2,6-dimethyl-N3,N5-bisaryl-1,4-dihydropyridine-3,5-dicarboxamides.

    PubMed

    Fassihi, Afshin; Azadpour, Zahra; Delbari, Neda; Saghaie, Lotfollah; Memarian, Hamid R; Sabet, Razieh; Alborzi, Abdolvahab; Miri, Ramin; Pourabbas, Bahman; Mardaneh, Jalal; Mousavi, Pegah; Moeinifard, Behzad; Sadeghi-Aliabadi, Hojjat

    2009-08-01

    A series of 4-substituted imidazolyl-2,6-dimethyl-N(3),N(5)-bisaryl-1,4-dihydropyridine-3,5-dicarboxamides were prepared. They were screened as antitubercular agents against Mycobacterium tuberculosis H(37)Rv. Minimum inhibitory concentrations (MICs) were determined using agar proportion method. Compound 3i with 1-benzyl-2-methylthio-1H-imidazole-5-yl substituent at C-4 position and 4'-chloromophenyl group at C-3 and C-5 positions of the 1,4-dihydropyridine ring was the most potent one among the tested compounds. It was as potent as rifampicin against M. tuberculosis H(37)RV. Compound 3l also was an active antitubercular agent with the same substituent as compound 3i at the C-4 position and 3'-pyridyl group at C-3 and C-5 positions of the 1,4-dihydropyridine ring.

  5. 2-Bromo-1-[1-(4-bromo­phen­yl)-5-methyl-1H-1,2,3-triazol-4-yl]ethanone

    PubMed Central

    Bunev, Alexander S.; Troshina, Marina A.; Ostapenko, Gennady I.; Pavlova, Andzhela P.; Khrustalev, Victor N.

    2014-01-01

    The asymmetric unit of the title compound, C11H9Br2N3O, contains two crystallographically independent mol­ecules with similar geometries; the Br—C—C=O torsion angles are 1.2 (4) and −2.8 (4)°, and the benzene and triazole rings are inclined o one another by 51.90 (16) and 51.88 (16)°. The two molecules are related by a pseudo-screw 21 axis directed along [100]. In the crystal, mol­ecules are linked into a three-dimensional network by weak C—H⋯O and C—H⋯N hydrogen bonds and secondary Br⋯Br [3.5991 (8) and 3.6503 (9) Å] inter­actions. PMID:25161595

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

    DOEpatents

    Ott, Donald G.; Benziger, Theodore M.

    1990-01-01

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

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

    DOEpatents

    Ott, Donald G.; Benziger, Theodore M.

    1991-01-01

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

  9. Inhibitory effects of LPA1 on cell motile activities stimulated by hydrogen peroxide and 2,3-dimethoxy-1,4-naphthoquinone in fibroblast 3T3 cells.

    PubMed

    Hirane, Miku; Araki, Mutsumi; Dong, Yan; Honoki, Kanya; Fukushima, Nobuyuki; Tsujiuchi, Toshifumi

    2013-11-08

    Reactive oxygen species (ROS) are known to mediate a variety of biological responses, including cell motility. Recently, we indicated that lysophosphatidic acid (LPA) receptor-3 (LPA3) increased cell motile activity stimulated by hydrogen peroxide. In the present study, we assessed the role of LPA1 in the cell motile activity mediated by ROS in mouse fibroblast 3T3 cells. 3T3 cells were treated with hydrogen peroxide and 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) at concentrations of 0.1 and 1 μM for 48 h. In cell motility assays with Cell Culture Inserts, the cell motile activities of 3T3 cells treated with hydrogen peroxide and DMNQ were significantly higher than those of untreated cells. 3T3 cells treated with hydrogen peroxide and DMNQ showed elevated expression levels of the Lpar3 gene, but not the Lpar1 and Lpar2 genes. To investigate the effects of LPA1 on the cell motile activity induced by hydrogen peroxide and DMNQ, Lpar1-overexpressing (3T3-a1) cells were generated from 3T3 cells and treated with hydrogen peroxide and DMNQ. The cell motile activities stimulated by hydrogen peroxide and DMNQ were markedly suppressed in 3T3-a1 cells. These results suggest that LPA signaling via LPA1 inhibits the cell motile activities stimulated by hydrogen peroxide and DMNQ in 3T3 cells.

  10. Molecular Recognition of CXCR4 by a Dual Tropic HIV-1 gp120 V3 Loop

    PubMed Central

    Tamamis, Phanourios; Floudas, Christodoulos A.

    2013-01-01

    HIV-1 cell entry is initiated by the interaction of the viral envelope glycoprotein gp120 with CD4, and chemokine coreceptors CXCR4 and CCR5. The molecular recognition of CXCR4 or CCR5 by the HIV-1 gp120 is mediated through the V3 loop, a fragment of gp120. The binding of the V3 loop to CXCR4 or CCR5 determines the cell tropism of HIV-1 and constitutes a key step before HIV-1 cell entry. Thus, elucidating the molecular recognition of CXCR4 by the V3 loop is important for understanding HIV-1 viral infectivity and tropism, and for the design of HIV-1 inhibitors. We employed a comprehensive set of computational tools, predominantly based on free energy calculations and molecular-dynamics simulations, to investigate the molecular recognition of CXCR4 by a dual tropic V3 loop. We report what is, to our knowledge, the first HIV-1 gp120 V3 loop:CXCR4 complex structure. The computationally derived structure reveals an abundance of polar and nonpolar intermolecular interactions contributing to the HIV-1 gp120:CXCR4 binding. Our results are in remarkable agreement with previous experimental findings. Therefore, this work sheds light on the functional role of HIV-1 gp120 V3 loop and CXCR4 residues associated with HIV-1 coreceptor activity. PMID:24048002

  11. Reactions of 1,3-Dibromo-1,1-difluoro Compounds with 1,8-Diazabicyclo[5.4.0]undec-7-ene.

    PubMed

    Elsheimer, Seth; Foti, Christopher J.; Bartberger, Michael D.

    1996-09-06

    Difluorodienes result from the double dehydrobromination of 4-aryl-1,3-dibromo-1,1-difluorobutanes with DBU. Attempted syntheses of analogous 4-alkyl or 4-alkoxy dienes yield monoelimination products under mild conditions and unexpected trifluoro compounds under more vigorous conditions. 4-Aryl-1,1-difluoro-1,3-butadienes react rapidly with 4-phenyl-1,2,4-triazoline-3,5-dione in Diels-Alder reactions, but these dienes are unreactive toward several other electron-deficient and electron-rich dienophiles.

  12. 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.

  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 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

  14. 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.

  15. Crystal structure of [tris-(4,4'-bi-pyridine)]-diium bis-(1,1,3,3-tetra-cyano-2-eth-oxy-propenide) trihydrate.

    PubMed

    Setifi, Fatima; Valkonen, Arto; Setifi, Zouaoui; Nummelin, Sami; Touzani, Rachid; Glidewell, Christopher

    2016-09-01

    The title hydrated salt, C30H26N6(2+)·2C9H5N4O(-)·3H2O, was obtained as an unexpected product from the hydro-thermal reaction between potassium 1,1,3,3-tetra-cyano-2-eth-oxy-propenide, 4,4'-bi-pyridine and iron(II) sulfate hepta-hydrate. The cation lies across a twofold rotation axis in the space group I2/a with the other components all in general positions. In the cation, the H atom linking the pyridine units is disordered over two adjacent sites having occupancies of 0.66 (4) and 0.36 (4), i.e. as N-H⋯N and N⋯H-N. The water mol-ecules of crystallization are each disordered over two sets of atomic sites, having occupancies of 0.522 (6) and 0.478 (6) for one, and 0.34 (3) and 0.16 (3) for the other, and it was not possible to reliably locate the H atoms associated with these partial-occupancy sites. In the crystal, four independent C-H⋯N hydrogen bonds link the ionic components into a three-dimensional network.

  16. Synaptic PI(3,4,5)P3 is required for Syntaxin1A clustering and neurotransmitter release.

    PubMed

    Khuong, Thang Manh; Habets, Ron L P; Kuenen, Sabine; Witkowska, Agata; Kasprowicz, Jaroslaw; Swerts, Jef; Jahn, Reinhard; van den Bogaart, Geert; Verstreken, Patrik

    2013-03-20

    PI(3,4,5)P3 is a low-abundance lipid thought to play a role in the regulation of synaptic activity; however, the mechanism remains obscure. We have constructed novel split Venus-based probes and used superresolution imaging to localize PI(3,4,5)P3 at Drosophila larval neuromuscular synapses. We find the lipid in membrane domains at neurotransmitter release sites, where it concentrates with Syntaxin1A, a protein essential for vesicle fusion. Reducing PI(3,4,5)P3 availability disperses Syntaxin1A clusters and increasing PI(3,4,5)P3 levels rescues this defect. In artificial giant unilamellar vesicles, PI(3,4,5)P3 also induces Syntaxin1A domain formation and this clustering, in vitro and in vivo, is dependent on positively charged residues in the Syntaxin1A-juxtamembrane domain. Functionally, reduced PI(3,4,5)P3 causes temperature-sensitive paralysis and reduced neurotransmitter release, a phenotype also seen in animals expressing a Syntaxin1A with a mutated juxtamembrane domain. Thus, our data indicate that PI(3,4,5)P3, based on electrostatic interactions, clusters Syntaxin1A at release sites to regulate neurotransmitter release.

  17. Palladium-catalyzed stereoselective intramolecular oxidative amidation of alkenes in the synthesis of 1,3- and 1,4-amino alcohols and 1,3-diamines.

    PubMed

    Malkov, Andrei V; Lee, Darren S; Barłóg, Maciej; Elsegood, Mark R J; Kočovský, Pavel

    2014-04-22

    An efficient and practical Pd-catalyzed intramolecular oxidative allylic amidation provides facile access to derivatives of 1,3- and 1,4-amino alcohols and 1,3-diamines. The method operates under mild reaction conditions (RT) with molecular oxygen (1 atm) as the sole reoxidant of Pd. Excellent diastereoselectivities were attained with substrates bearing a secondary stereogenic center.

  18. Synthesis and anti-mycobacterial activity of new 4-thiazolidinone and 1,3,4-oxadiazole derivatives of isoniazid.

    PubMed

    Bhat, Mashooq A

    2014-01-01

    A new series of 4-thiazolidinone (3a-e) and 1,3,4-oxadiazole (4a-e) derivatives of isoniazid were synthesized and evaluated for their in vitro anti-mycobacterial activity. The structures of the compounds were confirmed on the basis of spectral data and elemental analysis. Some compounds showed interesting activity against four Mycobacterium strains: M. intercellulari (ATCC 35743), M. xenopi (ATCC 14470), M. cheleneo (ATCC 35751) and M. smegmatis (ATCC 35797). Compounds 3e, N-(4-oxo-2-undecylthiazolidin-3-yl) isonicotinamide and 4e N-acetyl-4-(5-undecyl-1,3,4-oxadiazol-2-yl) pyridine with minimum inhibitory concentration (MIC), 6.0 μg/mL were found to be more potent than isoniazid under the in vitro investigational conditions. Compound 3e and 4e bear a high lipophilic chain bonded to the 5-position of the thiazolidinone and 1,3,4-oxadiazole moiety, respectively. This fact indicates that there exists a contribution of lipophilicity, which would facilitate the transport of these molecules through membranes.

  19. A new calmodulin-binding motif for inositol 1,4,5-trisphosphate 3-kinase regulation.

    PubMed

    Franco-Echevarría, Elsa; Baños-Sanz, Jose I; Monterroso, Begoña; Round, Adam; Sanz-Aparicio, Julia; González, Beatriz

    2014-11-01

    IP3-3K [Ins(1,4,5)P3 3-kinase] is a key enzyme that catalyses the synthesis of Ins(1,3,4,5)P4, using Ins(1,4,5)P3 and ATP as substrates. Both inositides, substrate and product, present crucial roles in the cell. Ins(1,4,5)P3 is a key point in Ca2+ metabolism that promotes Ca2+ release from intracellular stores and together with Ins(1,3,4,5)P4 regulates Ca2+ homoeostasis. In addition, Ins(1,3,4,5)P4 is involved in immune cell development. It has been proved that Ca2+/CaM (calmodulin) regulates the activity of IP3-3K, via direct interaction between both enzymes. Although we have extensive structural knowledge of the kinase domains of the three IP3-3K isoforms, no structural information is available about the interaction between IP3-3K and Ca2+/CaM. In the present paper we describe the crystal structure of the complex between human Ca2+/CaM and the CaM-binding region of human IP3-3K isoform A (residues 158-183) and propose a model for a complex including the kinase domain. The structure obtained allowed us to identify all of the key residues involved in the interaction, which have been evaluated by site-directed mutagenesis, pull-down and fluorescence anisotropy experiments. The results allowed the identification of a new CaM-binding motif, expanding our knowledge about how CaM interacts with its partners.

  20. New 1,3,4-bisthiadiazolines: synthesis, characterization and antimicrobial evaluations.

    PubMed

    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.

  1. 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.

  2. 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

  3. Epigenetic Determinants of CYP1A1 Induction by the Aryl Hydrocarbon Receptor Agonist 3,3',4,4',5-Pentachlorobiphenyl (PCB 126)

    PubMed Central

    Vorrink, Sabine U.; Hudachek, Danielle R.; Domann, Frederick E.

    2014-01-01

    Many enzymes involved in xenobiotic metabolism, including cytochrome P450 (CYP) 1A1, are regulated by the aryl hydrocarbon receptor (AhR). 3,3',4,4',5-Pentachlorobiphenyl (PCB 126) is a potent ligand for AhR and can thus induce the expression of CYP1A1. Interestingly, we observed that human carcinoma cell lines derived from different types of epithelial cells displayed divergent degrees of CYP1A1 induction after exposure to PCB 126. Since epigenetic mechanisms are known to be involved in cell type-specific gene expression, we sought to assess the epigenetic determinants of CYP1A1 induction in these carcinoma cell lines. In contrast to HepG2 hepatocarcinoma cells, HeLa cervical carcinoma cells showed significantly lower levels of CYP1A1 mRNA expression following PCB 126 exposure. Our results show that the two cell lines maintained differences in the chromatin architecture along the CYP1A1 promoter region. Furthermore, treatment with the epigenetic modifiers, trichostatin A (TSA) and 5-aza-2'-deoxycytidine (5-Aza-dC), significantly increased the expression of CYP1A1 after PCB 126 treatment in HeLa cells. However, we did not observe apparent differences in methylation levels or specific location of CpG DNA methylation between the two cell lines in the analyzed CYP1A1 promoter region. Taken together, our findings suggest that the differences in CYP1A1 expression between HepG2 and HeLa cells are due to differences in the chromatin architecture of the CYP1A1 promoter and thus establish a role of epigenetic regulation in cell-specific CYP1A1 expression. PMID:25116688

  4. Facile synthesis of Fe3O4/g-C3N4/HKUST-1 composites as a novel biosensor platform for ochratoxin A.

    PubMed

    Hu, Shuisheng; Ouyang, Wenjun; Guo, Longhua; Lin, Zhenyu; Jiang, Xiaohua; Qiu, Bin; Chen, Guonan

    2017-06-15

    A fluorescent biosensor for ochratoxin A was fabricated on the basis of a new nanocomposite (Fe3O4/g-C3N4/HKUST-1 composites). Fe3O4/g-C3N4/HKUST-1 was synthesized in this work for the first time, which combined HKUST-1 with g-C3N4 to improve its chemical stability. Fe3O4/g-C3N4/HKUST-1 composites have strong adsorption capacity for dye-labeled aptamer and are able to completely quench the fluorescence of the dye through the photoinduced electron transfer (PET) mechanism. In the presence of ochratoxin A (OTA), it can bind with the aptamer with high affinity, causing the releasing of the dye-labeled aptamer from the Fe3O4/g-C3N4/HKUST-1 and therefore results in the recovery of fluorescence. The fluorescence intensity of the biosensor has a linear relationship with the OTA concentration in the range of 5.0-160.0ng/mL. The LOD of sensor is 2.57ng/mL (S/N=3). This fluorescence sensor based on the Fe3O4/g-C3N4/HKUST-1 composites has been applied to detect OTA in corn with satisfying results.

  5. (2E)-2-[2-(4-Chloro-phen-yl)hydrazin-1-yl-idene]-4,4,4-trifluoro-3-oxobutanal.

    PubMed

    Huo, Yan-Ping; Zhou, Li-Hua

    2010-06-16

    The title compound, C(10)H(6)ClF(3)N(2)O(2), was synthesized by coupling 4-dimethyl-amino-1,1,1-trifluoro-but-3-en-2-one with 4-chloro-benzene-diazo-nium chloride. It crystallizes with two mol-ecules in the asymmetric unit, which form two similar centrosymmetric dimers via hydrogen bonds. Extensive electron delocalization and intra-molecular N-H⋯O hydrogen bonds are responsible for a planar conformation of the mol-ecules (maximum deviations = 0.010 and -0.015 Å for the two molecules). In addition to hydrogen bonds, π-π stacking inter-actions with centroid-centroid distances of 3.604 (2) and 3.583 (2) Å contribute to the stability of the crystal structure.

  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.

  7. 4-Salicylideneamino-3-methyl-1,2,4-triazole-5-thione as a sensor for aniline recognition.

    PubMed

    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.

  8. Open channel block of A-type, kv4.3, and delayed rectifier K+ channels, Kv1.3 and Kv3.1, by sibutramine.

    PubMed

    Kim, Sung Eun; Ahn, Hye Sook; Choi, Bok Hee; Jang, Hyun-Jong; Kim, Myung-Jun; Rhie, Duck-Joo; Yoon, Shin-Hee; Jo, Yang-Hyeok; Kim, Myung-Suk; Sung, Ki-Wug; Hahn, Sang June

    2007-05-01

    The effects of sibutramine on voltage-gated K+ channel (Kv)4.3, Kv1.3, and Kv3.1, stably expressed in Chinese hamster ovary cells, were investigated using the whole-cell patch-clamp technique. Sibutramine did not significantly decrease the peak Kv4.3 currents, but it accelerated the rate of decay of current inactivation in a concentration-dependent manner. This phenomenon was effectively characterized by integrating the total current over the duration of a depolarizing pulse to +40 mV. The IC50 value for the sibutramine block of Kv4.3 was 17.3 microM. Under control conditions, the inactivation of Kv4.3 currents could be fit to a biexponential function, and the time constants for the fast and slow components were significantly decreased after the application of sibutramine. The association (k+1) and dissociation (k-1) rate constants for the sibutramine block of Kv 4.3 were 1.51 microM-1s-1 and 27.35 s-1, respectively. The theoretical KD value, derived from k-1/k+1, yielded a value of 18.11 microM. The block of Kv4.3 by sibutramine displayed a weak voltage dependence, increasing at more positive potentials, and it was use-dependent at 2 Hz. Sibutramine did not affect the time course for the deactivating tail currents. Neither steady-state activation and inactivation nor the recovery from inactivation was affected by sibutramine. Sibutramine caused the concentration-dependent block of the Kv1.3 and Kv3.1 currents with an IC50 value of 3.7 and 32.7 microM, respectively. In addition, sibutramine reduced the tail current amplitude and slowed the deactivation of the tail currents of Kv1.3 and Kv3.1, resulting in a crossover phenomenon. These results indicate that sibutramine acts on Kv4.3, Kv1.3, and Kv3.1 as an open channel blocker.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Context dependency of Set1/COMPASS-mediated histone H3 Lys4 trimethylation

    PubMed Central

    Thornton, Janet L.; Westfield, Gerwin H.; Takahashi, Yoh-hei; Cook, Malcolm; Gao, Xin; Woodfin, Ashley R.; Lee, Jung-Shin; Morgan, Marc A.; Jackson, Jessica; Smith, Edwin R.; Couture, Jean-Francois; Skiniotis, Georgios; Shilatifard, Ali

    2014-01-01

    The stimulation of trimethylation of histone H3 Lys4 (H3K4) by H2B monoubiquitination (H2Bub) has been widely studied, with multiple mechanisms having been proposed for this form of histone cross-talk. Cps35/Swd2 within COMPASS (complex of proteins associated with Set1) is considered to bridge these different processes. However, a truncated form of Set1 (762-Set1) is reported to function in H3K4 trimethylation (H3K4me3) without interacting with Cps35/Swd2, and such cross-talk is attributed to the n-SET domain of Set1 and its interaction with the Cps40/Spp1 subunit of COMPASS. Here, we used biochemical, structural, in vivo, and chromatin immunoprecipitation (ChIP) sequencing (ChIP-seq) approaches to demonstrate that Cps40/Spp1 and the n-SET domain of Set1 are required for the stability of Set1 and not the cross-talk. Furthermore, the apparent wild-type levels of H3K4me3 in the 762-Set1 strain are due to the rogue methylase activity of this mutant, resulting in the mislocalization of H3K4me3 from the promoter-proximal regions to the gene bodies and intergenic regions. We also performed detailed screens and identified yeast strains lacking H2Bub but containing intact H2Bub enzymes that have normal levels of H3K4me3, suggesting that monoubiquitination may not directly stimulate COMPASS but rather works in the context of the PAF and Rad6/Bre1 complexes. Our study demonstrates that the monoubiquitination machinery and Cps35/Swd2 function to focus COMPASS's H3K4me3 activity at promoter-proximal regions in a context-dependent manner. PMID:24402317

  14. Synthesis and evaluation of the biological activities of some 3-{[5-(6-methyl-4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3,4-oxadiazol-2-yl]-imino}-1,3-dihydro-2H-indol-2-one derivatives.

    PubMed

    George, Sonia; Parameswaran, Manoj Kumar; Chakraborty, Acharjee Raja; Ravi, Thengungal Kochupappy

    2008-03-01

    Reaction of ethyl-6-methyl-2-oxo-4-aryl-1,2,3,4-tetrahydropyrimidin-5-carboxylates (1a-i) with hydrazine hydrate yielded 6-methyl-2-oxo-4-aryl-1,2,3,4-tetrahydropyrimidin-5-carbohydrazides (2a-i). These products, on reaction with cyanogen bromide, gave 5-(5-amino-1,3,4-oxadiazol-2-yl)-6-methyl-4-aryl-3,4-dihydropyrimidin-2 (1H)-ones (3a-i). The resultant aminooxadiazolylpyrimidinones were condensed with isatin to obtain various 3-{[5-(6-methyl-4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3,4-oxadiazol-2-yl]-imino}-1,3-dihydro-2H-indol-2-ones (4a-i). These products were characterized by IR, 1H NMR, mass spectra and elemental analysis. Products (4a-i) revealed promising antibacterial, antifungal and antioxidant activity.

  15. Properties of 2,3, and 2″,3″-difluorosubstituted 4″-alkyl[1,1':4',1″]terphenyl-4-yl alkyl carbonates with SmC phase

    NASA Astrophysics Data System (ADS)

    Chołuj, A.; Szczuciński, Ł.; Milewska, K.; Kula, P.; Dąbrowski, R.; Mazur, R.; Piecek, W.

    2014-08-01

    In the paper is presented the influence of different orthodifluorosubstitution on the mesomorphic properties of 4″-alkyl[1,1‧:4‧,1″]terphenyl-4-yl alkyl carbonates described by general formulae presented below: ? where X1;2 (acronym nFFTm) or X3;4 = F (acronym nTFFm). Phase transition was studied by differential scanning calorimetry (DSC) and microscopic methods. Compounds exhibit nematic and smectic phases: SmA, SmC, G and H. Mixture with smectic SmC phase in wide temperature range was prepared using these carbonates. Its physical and electro-optic properties are shown and discussed.

  16. 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

    NASA Astrophysics Data System (ADS)

    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 IC50 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.

  17. 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.

  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. 5,7-Di-2-pyridyl-2,3-dihydro-thieno[3,4-b][1,4]dioxine.

    PubMed

    Djukic, Brandon; Harrington, Laura E; Britten, James F; Lemaire, Martin T

    2008-01-16

    The title compound, C(16)H(12)N(2)O(2)S, was prepared by a Neigishi cross-coupling reaction to investigate the coordination chemistry of thio-phene-containing ligands. In the mol-ecule, the pyridine rings are twisted from the thio-phene ring by 20.6 (1) and 4.1 (2)°. The six-membered dihydro-dioxine ring is in a half-chair conformation.

  20. Investigation of the association behaviors between bovine serum albumin and 2-(4-methylphenyl)-3-(N-acetyl)-5-(2,4-dichlorophenoxymethyl)-1,3,4-oxodiazoline.

    PubMed

    Huang, Zhenzhong; Wang, Ruiling; Han, Erwei; Xu, Lifan; Song, Yonghai

    2013-07-01

    The study was designed to examine the interaction between 2-(4-methylphenyl)-3-(N-acetyl)-5-(2,4-dichlorophenoxymethyl)-1,3,4-oxodiazoline (MPNDO) and bovine serum albumin (BSA) under physiological conditions by using fluorescence spectroscopy, ultraviolet absorption spectroscopy, FT-IR spectroscopy and circular dichroism spectroscopy and atomic force microscope. Spectroscopic analysis of the fluorescence emission quenching and ultraviolet absorption revealed that the quenching mechanism of bovine serum albumin by MPNDO was static quenching procedure. The binding constant and binding sites number at different temperatures were measured. The average binding distances between donor (BSA) and acceptor (MPNDO) was estimated to be 1.46 nm (301 K), based on the Föster non-radioactive energy transfer theory. An average size of 3.1 nm had a high proportion and these dots might be ascribed to BSA, some other dots with an average size of 6.6 nm might result from BSA-MPNDO bioconjugates while the average diameter of MPNDO was 1.6 nm, which was reasonable to conclude that one BSA-MPNDO bioconjugates consisted of one BSA and one MPNDO. The thermodynamic parameters, enthalpy change (ΔH), entropy change (ΔS) and free energy change (ΔG) were calculated, which indicated that the action force was mainly van der Waals forces. The data collected through synchronous fluorescence, FT-IR spectroscopy and circular dichroism spectroscopy demonstrated that the conformation of BSA was not affected obviously in the presence of MPNDO.

  1. Structural and optical properties of NdxGd1-xCr3(BO3)4 solid solutions

    NASA Astrophysics Data System (ADS)

    Dobretsova, E. A.; Boldyrev, K. N.; Borovikova, E. Yu.; Chernyshev, V. A.

    2016-12-01

    The spectroscopic investigation of the solid solutions GdCr3(BO3)4 (sp.gr. R32) - NdCr3(BO3)4 (sp.gr. C2/c) is presented. The single crystals NdxGd1-xCr3(BO3)4, 0≤x≤1 with the step of 0.1, were grown by a flux method. Crystal structures were identified by terahertz and optical spectroscopy methods. Ab initio calculations in the frame of density functional theory allowed us to separate modes belonging to the R32 and C2/c phases and to estimate the ratio of these phases in NdxGd1-xCr3(BO3)4 crystals. Content of the monoclinic phase (C2/c) increases with growth of the Nd concentration.

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

    SciTech Connect

    Bayless, Paul D.

    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.

  3. 2-Sulfanylidene-1,3-dithiolo[4,5-b]naphtho­[2,3-e][1,4]dithiine-5,10-dione

    PubMed Central

    Méndez-Rojas, Miguel Angel; Bernès, Sylvain; Pérez-Benítez, Aarón; Romero Zarazúa, María Fernanda; Castellanos-Uribe, Adrián

    2011-01-01

    The title mol­ecule, C13H4O2S5, is folded by 47.83 (6)° along the S⋯S vector of the [1,4]dithiine six-membered ring, with the naphtho­quinone and [1,3]dithiole-2-thione moieties being nearly planar [largest deviations from least-squares planes = 0.028 (2) and 0.016 (1) Å, respectively]. This boat conformation is close to that observed in the analogous compound [Mendez-Rojas et al. (2001). J. Chem. Crystallogr. 31, 17–28] including a 2-oxo group [folding angle: 42.3 (1)° at 213 (2) K]. Both compounds are indeed isomorphous, and the small difference in the folding angle probably results from the involvement of the thioxo group of the title compound in inter­molecular S⋯S contacts [3.5761 (13) Å]. In the crystal structure, mol­ecules are stacked in the [100] direction, with dithiole rings making π–π inter­actions. In a stack, alternating short and long separations are observed between the centroids of dithiole rings, 3.5254 (17) and 4.7010 (18) Å. PMID:22219881

  4. 8-acenaphthen-1-yl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one derivatives as orphanin FQ receptor agonists.

    PubMed

    Wichmann, J; Adam, G; Röver, S; Cesura, A M; Dautzenberg, F M; Jenck, F

    1999-08-16

    A series of 8-acenaphthen-1-yl-1-phenyl-1,3,8-triaza-spiro[4.5]decan+ ++-4-one derivatives 1 was studied with respect to the binding affinity for the orphanin FQ (OFQ) and opioid (mu, kappa, delta) receptors. The influence of stereochemistry as well as the substitution pattern of the phenyl-ring in position 1 on the affinity for the orphanin FQ receptor and selectivity to opioid (mu, kappa, delta) receptors is discussed. The most interesting compound 1c was tested for its anxiolytic-like properties in vivo.

  5. Synthesis and crystal structures of 7-bromo-5-(2‧-chloro)phenyl-3-hydroxy-1-methyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one and 7-bromo-5-(2‧-chloro)phenyl-1-hexyl-1,2,4,5-tetrahydro-3H-1,4-benzodiazepin-2,3-dione

    NASA Astrophysics Data System (ADS)

    Kravtsov, Victor Ch.; Fonari, Marina S.; Gdaniec, Мaria; Pavlovsky, Victor I.; Andronati, Sergei A.; Semenishyna, Ekaterina A.

    2012-06-01

    Treatment of 7-bromo-5-(2'-chloro)phenyl-3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one (1) with methyl or hexyl tosylate resulted in 7-bromo-5-(2'-chloro)phenyl-3-hydroxy-1-methyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one (2) and 7-bromo-5-(2'-chloro)phenyl-1-hexyl-1,2,4,5-tetrahydro-3H-1,4-benzodiazepin-2,3-dione (3). As confirmed by X-ray crystallography, the two products differ not only in the identity of the alkyl substituent in position 1 of the benzodiazepine fragment but also crystallize in different molecular forms resulting from proton migration. This alteration of the molecular structure leads to a significant change in the conformation of the central molecular fragment and influences the assembly mode in the crystal. In 3, centrosymmetric dimers formed via a pair of Nsbnd H⋯O hydrogen bonds are further linked into chains via Csbnd Br⋯Odbnd C halogen bond interaction. In turn in 2 there are two symmetry independent molecules, each giving a different set of intermolecular interactions. One of the molecules forms a dimer via Osbnd H⋯O interactions whereas the second one generates chain via Csbnd Br⋯Odbnd C halogen bond that is also assisted by a weak Osbnd H⋯Br hydrogen bond.

  6. Imidazole clubbed 1,3,4-oxadiazole derivatives as potential antifungal agents.

    PubMed

    Wani, Mohmmad Younus; Ahmad, Aijaz; Shiekh, Rayees Ahmad; Al-Ghamdi, Khalaf J; Sobral, Abilio J F N

    2015-08-01

    A series of compounds in which 2-(4-ethyl-2-pyridyl)-1H-imidazole was clubbed with substituted 1,3,4-oxadiazole was synthesized and subjected to antifungal activity evaluation. In vitro assays indicated that several clubbed derivatives had excellent antifungal activity against different strains of laboratory and clinically isolated Candida species. Structural Activity Relationship (SAR) studies revealed that the presence and position of substituents on the phenyl ring of the 1,3,4-oxadiazole unit, guides the antifungal potential of the compounds, where compound 4b, 4c and 4g were found to be active against all the tested fungal strains. Impairment of ergosterol biosynthesis upon the concomitant treatment of 4b, 4c and 4g, revealed the possible mechanisms of antifungal action of these compounds. Inhibitors snugly fitting the active site of the target enzyme, as revealed by molecular docking studies, may well explain their excellent inhibitory activity.

  7. 3,3'-(Ethylenedioxy)dipropiononitrile as an Electrolyte Additive for 4.5 V LiNi1/3Co1/3Mn1/3O2/Graphite Cells.

    PubMed

    Wang, Chengyun; Yu, Le; Fan, Weizhen; Liu, Jiangwen; Ouyang, Liuzhang; Yang, Lichun; Zhu, Min

    2017-03-22

    3,3'-(Ethylenedioxy)dipropiononitrile (EDPN) has been introduced as a novel electrolyte additive to improve the oxidation stability of the conventional carbonate-based electrolyte for LiNi1/3Co1/3Mn1/3O2/graphite pouch batteries cycled under high voltage. Mixing 0.5 wt % EDPN into the electrolyte greatly improved the capacity retention, from 32.5% to 83.9%, of cells cycled for 100 times in the range 3.0-4.5 V with a rate of 1C. The high rate performance (3C and 5C) was also improved, while the cycle performance was similar to that of the cell without EDPN when cycled between 3.0 and 4.2 V. Further evidence of a stable protective interphase film can be formed on the LiNi1/3Co1/3Mn1/3O2 electrode surface due to the presence of EDPN in the electrolyte. This process effectively suppresses the oxidative decomposition of electrolyte and the growth in the charge-transfer resistance of the LiNi1/3Co1/3Mn1/3O2 electrode and greatly improves the high-voltage electrochemical properties for the cells. In contrast, EDPN has no positive effect on the cyclic performance of the LiNi0.5Co0.2Mn0.3O2-based cell under high operating voltage.

  8. 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.

  9. 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.

  10. Identification of 4-(3-Pyridyl)-4-oxobutyl-2'-deoxycytidine Adducts Formed in the Reaction of DNA with 4-(Acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone: A Chemically Activated Form of Tobacco-Specific Carcinogens.

    PubMed

    Michel, Anna K; Zarth, Adam T; Upadhyaya, Pramod; Hecht, Stephen S

    2017-03-31

    Metabolic activation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 1) and N'-nitrosonornicotine (NNN, 2) results in the formation of 4-(3-pyridyl)-4-oxobutyl (POB)-DNA adducts, several of which have been previously identified both in vitro and in tissues of laboratory animals treated with NNK or NNN. However, 2'-deoxycytidine adducts formed in this process have been incompletely examined in previous studies. Therefore, in this study we prepared characterized standards for the identification of previously unknown 2'-deoxycytidine and 2'-deoxyuridine adducts that could be produced in these reactions. The formation of these products in reactions of 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc, 3), a model 4-(3-pyridyl)-4-oxobutylating agent, with DNA was investigated. The major 2'-deoxycytidine adduct, identified as its stable cytosine analogue O(2)-[4-(3-pyridyl)-4-oxobut-1-yl]-cytosine (12), was O(2)-[4-(3-pyridyl)-4-oxobut-1-yl]-2'-deoxycytidine (13), whereas lesser amounts of 3-[4-(3-pyridyl)-4-oxobut-1-yl]-2'-deoxycytidine (14) and N(4)-[4-(3-pyridyl)-4-oxobut-1-yl]-2'-deoxycytidine (15) were also observed. The potential conversion of relatively unstable 2'-deoxycytidine adducts to stable 2'-deoxyuridine adducts by treatment of the adducted DNA with bisulfite was also investigated, but the harsh conditions associated with this approach prevented quantitation. The results of this study provide new validated standards for the study of 4-(3-pyridyl)-4-oxobutylation of DNA, a critical reaction in the carcinogenesis by 1 and 2, and demonstrate the presence of previously unidentified 2'-deoxycytidine adducts in this DNA.

  11. Identification of 4-(3-Pyridyl)-4-oxobutyl-2′-deoxycytidine Adducts Formed in the Reaction of DNA with 4-(Acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone: A Chemically Activated Form of Tobacco-Specific Carcinogens

    PubMed Central

    2017-01-01

    Metabolic activation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 1) and N′-nitrosonornicotine (NNN, 2) results in the formation of 4-(3-pyridyl)-4-oxobutyl (POB)-DNA adducts, several of which have been previously identified both in vitro and in tissues of laboratory animals treated with NNK or NNN. However, 2′-deoxycytidine adducts formed in this process have been incompletely examined in previous studies. Therefore, in this study we prepared characterized standards for the identification of previously unknown 2′-deoxycytidine and 2′-deoxyuridine adducts that could be produced in these reactions. The formation of these products in reactions of 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc, 3), a model 4-(3-pyridyl)-4-oxobutylating agent, with DNA was investigated. The major 2′-deoxycytidine adduct, identified as its stable cytosine analogue O2-[4-(3-pyridyl)-4-oxobut-1-yl]-cytosine (12), was O2-[4-(3-pyridyl)-4-oxobut-1-yl]-2′-deoxycytidine (13), whereas lesser amounts of 3-[4-(3-pyridyl)-4-oxobut-1-yl]-2′-deoxycytidine (14) and N4-[4-(3-pyridyl)-4-oxobut-1-yl]-2′-deoxycytidine (15) were also observed. The potential conversion of relatively unstable 2′-deoxycytidine adducts to stable 2′-deoxyuridine adducts by treatment of the adducted DNA with bisulfite was also investigated, but the harsh conditions associated with this approach prevented quantitation. The results of this study provide new validated standards for the study of 4-(3-pyridyl)-4-oxobutylation of DNA, a critical reaction in the carcinogenesis by 1 and 2, and demonstrate the presence of previously unidentified 2′-deoxycytidine adducts in this DNA. PMID:28393135

  12. Exocyclic Deoxyadenosine Adducts of 1,2,3,4-Diepoxybutane: Synthesis, Structural Elucidation, and Mechanistic Studies

    PubMed Central

    Seneviratne, Uthpala; Antsypovich, Sergey; Goggin, Melissa; Dorr, Danae Quirk; Guza, Rebecca; Moser, Adam; Thompson, Carrie; York, Darrin M.; Tretyakova, Natalia

    2009-01-01

    1,2,3,4-Diepoxybutane (DEB)1 is considered the ultimate carcinogenic metabolite of 1,3-butadiene, an important industrial chemical and environmental pollutant present in urban air. Although it preferentially modifies guanine within DNA, DEB induces a large number of A → T transversions, suggesting that it forms strongly mispairing lesions at adenine nucleobases. We now report the discovery of three potentially mispairing exocyclic adenine lesions of DEB: N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (compound 2), 1,N6-(2-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2′-deoxyadenosine (compound 3), and 1,N6-(1-hydroxymethyl-2-hydroxypropan-1,3-diyl)-2′-deoxyadenosine (compound 4). The structures and stereochemistry of the novel DEB-dA adducts were determined by a combination of UV and NMR spectroscopy, tandem mass spectrometry, and independent synthesis. We found that synthetic N6-(2-hydroxy-3,4-epoxybut-1-yl)-2′-deoxyadenosine (compound 1) representing the product of N6-adenine alkylation by DEB spontaneously cyclizes to form 3 under aqueous conditions or 2 under anhydrous conditions in the presence of organic base. Compound 3 can be interconverted with 4 by a reversible unimolecular pericyclic reaction favoring 4 as a more thermodynamically stable product. Both 3 and 4 are present in double stranded DNA treated with DEB in vitro and in liver DNA of laboratory mice exposed to 1,3-butadiene by inhalation. We propose that in DNA under physiological conditions, DEB alkylates the N-1 position of adenine in DNA to form N1-(2-hydroxy-3,4-epoxybut-1-yl)-adenine adducts, which undergo an SN2-type intramolecular nucleophilic substitution and rearrangement to give 3 (minor) and 4 (major). Formation of exocyclic DEB-adenine lesions following exposure to 1,3-butadiene provides a possible mechanism of mutagenesis at the A:T base pairs. PMID:19883087

  13. Synthesis and anti-inflammatory activity evaluation of some novel 6-alkoxy(phenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-amine derivatives.

    PubMed

    Sun, Xian-Yu; Hu, Chuan; Deng, Xian-Qing; Wei, Cheng-Xi; Sun, Zhi-Gang; Quan, Zhe-Shan

    2010-11-01

    Starting from phthalic anhydride, several new 6-alkoxy(phenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-amine derivatives were synthesized as potent anti-inflammatory agent. The study showed that the compounds 6h (6-(2-chlorophenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-amine) and 6s (6-(4-aminophenoxy)-[1,2,4] triazolo[3,4-a]phthalazine-3-amine) exhibited the highest anti-inflammatory activity (81% and 83% inhibition, respectively, at 0.5 h after i.p. administration) which were slightly more potent than the reference drug Ibuprofen (61%). Furthermore, the peak activity of 6h and 6s was observed at the 3 h after p.o. administration, and they exhibited stronger anti-inflammatory activity than Ibuprofen at the dose of 50 mg/kg at the peak time.

  14. Oxa-ene reaction of enols of amides with 4-phenyl-1,2,4-triazoline-3,5-dione.

    PubMed

    Basheer, Ahmad; Rappoport, Zvi

    2008-01-04

    The reaction of 16 enols of amides with 4-phenyl-1,2,4-triazoline-1,3-dione gave open chain adducts rather than the [2 + 2] cycloadducts with a hemiaminal moiety, both in solid state and in solution. This assignment is based on X-ray crystallography, (1)H and (13)C NMR data, and IR spectra. The suggested mechanism involves hydroxyl proton loss in a formal oxa-ene reaction. Mechanistic details and a possible alternative are discussed.

  15. Recent Advancements In 1, 4-Disubstituted 1H-1,2,3-Triazoles As Potential Anticancer Agents.

    PubMed

    Lal, Kashmiri; Yadav, Pinki

    2016-08-11

    Cancer is a class of formidable disease with a high degree of mortality. Although, there has been much progress in chemotherapy still the problem of drug resistance has led to the search for newer leads with superior efficacy. 1,2,3-Triazole are among a vast number of nitrogen containing heterocycles studied extensively as pharmacologically important scaffolds. Recently developed copper (I)-catalyzed cycloaddition reaction between organic azides and terminal alkynes yielding 1,4-disubstituted 1,2,3-triazoles has attracted considerable attention because it allows the construction of vast array of 1,2,3-triazoles with significant potential in pharmaceutical chemistry. In this article, an attempt to summarize the wide range of anticancer agents derived from Copper(I)-Catalyzed azide alkyne cycloaddition reported by the authors worldwide has been made. This review includes articles published from 2010 onwards and summarizes the recent progress on the development of 1,4-disubstituted 1H-1,2,3-triazole as novel anticancer chemotypes with high therapeutic indices.

  16. 1,3,4-oxadiazole: a privileged structure in antiviral agents.

    PubMed

    Li, Z; Zhan, P; Liu, X

    2011-11-01

    1,3,4-oxadiazole, a privileged structure, endows its derivatives with broad and potent biological functions, especially in antiviral activities, including anti-HIV, anti-HCV, anti-HBV, anti-HSV activities, etc. Molecular modeling and pharmacokinetic studies have demonstrated that the introduction of 1,3,4-oxadiazole ring to the inhibitors can change their polarity, flexibility as well as metabolic stability, and 1,3,4-oxadiazole scaffold can also act as acceptors of hydrogen bonds formation, which make it possible to be used as a isosteric substituent for amide or ester groups. This review focuses on the recent advances in the synthesis of 1,3,4-oxadiazole ring and mainly the discovery, biological activities investigations and structural modifications of several distinct classes of 1,3,4-oxadiazoles as potent antiviral agents. In addition, the binding models of some representative 1,3,4-oxadiazoles were also discussed, which provide rational explanation for their interesting antiviral activities, and also pave the way for further optimization of 1,3,4- oxadiazole based antiviral agents.

  17. Metal complexes with some 3-aryl-1,2,4-oxadiazoles

    NASA Astrophysics Data System (ADS)

    Massacesi, Marcella; Devoto, Gerolamo; Gelli, Gioanna

    1985-01-01

    Complexes of empirical formula M(L) 2X 2 were synthesized and characterized, where L = 5-methyl-3-(2,4,6-trimethoxiphenyl)-1,2,4-oxadiazole (topho), M = Zn(II), Cu(II), Co(II), Pd(II), Pt(II), X = Cl, M = Pd(II), Pt(II), X = Br, M = Zn(II), X = I; L = 5-methy]-3-(3,5-dichloro,2,4,6-trimethyl-phenyl)-1,2,4-oxadiazole (ctpho), M = Cu(II), Co(II), X = Cl; L = 5-methyl-3-(2,4,6-trimethylphenyl)-1,2,4-oxadiazole (tpho), M = Cu(II), X = Cl. Magnetic, spectral, conductivity and elemental analysis data indicate that the ligands always act as monodentate, N-bonded. The Pd(II) and Pt(II) complexes are square planar and all the other derivatives are tetrahedral.

  18. Formation of 1,2:3,4-Diepoxybutane-Specific Hemoglobin Adducts in 1,3-Butadiene Exposed Workers

    PubMed Central

    Boysen, Gunnar; Georgieva, Nadia I.; Bordeerat, Narisa K.; Šram, Radim J.; Vacek, Pamela; Albertini, Richard J.; Swenberg, James A.

    2012-01-01

    1,3-Butadiene (BD) is an important industrial chemical that is classified as a human carcinogen. BD carcinogenicity has been attributed to its metabolism to several reactive epoxide metabolites and formation of the highly mutagenic 1,2:3,4-diepoxybutane (DEB) has been hypothesized to drive mutagenesis and carcinogenesis at exposures experienced in humans. We report herein the formation of DEB-specific N,N-(2,3-dihydroxy-1,4-butadiyl)valine (pyr-Val) in BD-exposed workers as a biomarker of DEB formation. pyr-Val was determined in BD monomer and polymer plant workers that had been previously analyzed for several other biomarkers of exposure and effect. pyr-Val was detected in 68 of 81 (84%) samples ranging from 0.08 to 0.86 pmol/g globin. Surprisingly, pyr-Val was observed in 19 of 23 administrative control subjects not known to be exposed to BD, suggesting exposure from environmental sources of BD. The mean ± SD amounts of pyr-Val were 0.11 ± 0.07, 0.16 ± 0.12, and 0.29 ± 0.20 pmol/g globin in the controls, monomer, and polymer workers, respectively, clearly demonstrating formation of DEB in humans. The amounts of pyr-Val found in this study suggest that humans are much less efficient in the formation of DEB than mice or rats at similar exposures. Formation of pyr-Val was more than 50-fold lower than has been associated with increased mutagenesis in rodents. The results further suggest that formation of DEB relative to other epoxides is significantly different in the highest exposed polymer workers compared with controls and BD monomer workers. Whether this is due to saturation of metabolic formation or increased GST-mediated detoxification could not be determined. PMID:22003190

  19. 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.

  20. Antimicrobial activity of quinoxaline 1,4-dioxide with 2- and 3-substituted derivatives.

    PubMed

    Vieira, Mónica; Pinheiro, Cátia; Fernandes, Rúben; Noronha, João Paulo; Prudêncio, Cristina

    2014-04-01

    Quinoxaline is a chemical compound that presents a structure that is similar to quinolone antibiotics. The present work reports the study of the antimicrobial activity of quinoxaline N,N-dioxide and some derivatives against bacterial and yeast strains. The compounds studied were quinoxaline-1,4-dioxide (QNX), 2-methylquinoxaline-1,4-dioxide (2MQNX), 2-methyl-3-benzoylquinoxaline-1,4-dioxide (2M3BenzoylQNX), 2-methyl-3-benzylquinoxaline-1,4-dioxide (2M3BQNX), 2-amino-3-cyanoquinoxaline-1,4-dioxide (2A3CQNX), 3-methyl-2-quinoxalinecarboxamide-1,4-dioxide (3M2QNXC), 2-hydroxyphenazine-N,N-dioxide (2HF) and 3-methyl-N-(2-methylphenyl)quinoxalinecarboxamide-1,4-dioxide (3MN(2MF)QNXC). The prokaryotic strains used were Staphylococcus aureus ATCC 6538, S. aureus ATCC 6538P, S. aureus ATCC 29213, Escherichia coli ATCC 25922, E. coli S3R9, E. coli S3R22, E. coli TEM-1 CTX-M9, E. coli TEM-1, E. coli AmpC Mox-2, E. coli CTX-M2 e E. coli CTX-M9. The Candida albicans ATCC 10231 and Saccharomyces cerevisiae PYCC 4072 were used as eukaryotic strains. For the compounds that presented activity using the disk diffusion method, the minimum inhibitory concentration (MIC) was determined. The alterations of cellular viability were evaluated in a time-course assay. Death curves for bacteria and growth curves for S. cerevisiae PYCC 4072 were also accessed. The results obtained suggest potential new drugs for antimicrobial activity chemotherapy since the MIC's determined present low values and cellular viability tests show the complete elimination of the bacterial strain. Also, the cellular viability tests for the eukaryotic model, S. cerevisiae, indicate low toxicity for the compounds tested.

  1. Novel synthetic (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol inhibits arthritis by targeting signal transducer and activator of transcription 3

    PubMed Central

    Son, Dong Ju; Kim, Dae Hwan; Nah, Seong-Su; Park, Mi Hee; Lee, Hee Pom; Han, Sang Bae; Venkatareddy, Udumula; Gann, Benjamin; Rodriguez, Kevin; Burt, Scott R.; Ham, Young Wan; Jung, Yu Yeon; Hong, Jin Tae

    2016-01-01

    Rheumatoid arthritis (RA) is a severely debilitating chronic autoimmune disease that leads to long-term joint damage. Signal transducer and activator of transcription 3 (STAT3)-targeted small molecules have shown promise as therapeutic drugs for treating RA. We previously identified (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (BHPB), a tyrosine-fructose Maillard reaction product, as a small molecule with potent anti-inflammatory and anti-arthritic properties, mediated through the inhibition of STAT3 activation. The aim of this study was to develop a novel BHPH derivative with improved anti-arthritic properties and drug-likeness. We designed and synthesised (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP), a novel synthetic BHPB analogue, and investigated its anti-inflammatory and anti-arthritic activities in experimentally-induced RA. We showed that MMPP strongly inhibited pro-inflammatory responses by inhibiting in vitro STAT3 activation and its downstream signalling in murine macrophages and human synoviocytes from patients with RA. Furthermore, we demonstrated that MMPP exhibited potent anti-arthritic activity in a collagen antibody-induced arthritis (CAIA) mouse model in vivo. Collectively, our results suggest that MMPP has great potential for use in the treatment of RA. PMID:27845373

  2. The First Coordination Polymers Based on 1,3‐Diphosphaferrocenes and 1,1′,2,3′,4‐Pentaphosphaferrocenes†

    PubMed Central

    Heindl, Claudia; Reisinger, Sabine; Schwarzmaier, Christoph; Rummel, Lena; Virovets, Alexander V.; Peresypkina, Eugenia V.

    2015-01-01

    Abstract Phosphaferrocenes in combination with coinage metal salts proved to be excellent building blocks in supramolecular chemistry for the buildup of oligomeric and polymeric assemblies. The synthesis of a series of novel phosphaferrocenes containing the 1,3‐P2C3 iPr3 and/or the 1,2,4‐P3C2 iPr2 ligand is described herein. The self‐assembly processes of the 1,3‐diphospha‐, 1,2,4‐triphospha‐, and 1,1′,2,3′,4‐pentaphosphaferrocenes with CuI halides led to the formation of 1D or 2D polymers. With [Cp*Fe(η5‐P2C3 iPr3)] (Cp* = η5‐C5Me5), infinite chains are formed, whereas with [(η5‐P3C2 iPr2)Fe(η5‐P2C3 iPr3)] 1D ladderlike structures are obtained. These are the first polymers containing such a di‐ and pentaphosphaferrocene, respectively. On the other hand, the use of [Cp*Fe(η5‐P3C2 iPr2)] leads to the construction of 2D networks with intact sandwich complexes, which is uncommon for this class of complexes. PMID:27134554

  3. 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... his wife is less than $5,000, and if each is required to file a return, the husband and the wife...

  4. Pelanserin: 3-[3-(4-phenyl­piperazin-1-yl)prop­yl]quinazoline-2,4(1H,3H)-dione

    PubMed Central

    Aguirre Hernández, Gerardo; Somanathan, Ratnasamy; Bernès, Sylvain

    2014-01-01

    The title compound, C21H24N4O2, is a potent serotonin 5-HT2 and α1-adrenoceptor antagonist. The n-propyl chain links the quinazolinedione heterocycle and the phenyl­piperazine group in which the benzene ring is equatorially located and the piperazine ring has the expected chair conformation. The dihedral angle between the planes of the benzene ring and the quinazolinedione ring system is 74.1 (1)°. In the crystal, mol­ecules form centrosymmetric dimers through R 2 2(8) hydrogen-bonded rings involving the amine and one carbonyl group of the quinazolinedione moiety. These dimers are extended into chains extending along the a-axis direction through expanded centrosymmetric cyclic C—H⋯O associations involving the second carbonyl group, giving R 2 2(20) and R 1 2(7) motifs. PMID:25249922

  5. 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...

  6. Antiinflammatory 2-benzyl-4-sulfonyl-4H-isoquinoline-1,3-diones: novel inhibitors of COX-2.

    PubMed

    Lazer, E S; Sorcek, R; Cywin, C L; Thome, D; Possanza, G J; Graham, A G; Churchill, L

    1998-05-19

    A series of 2-benzyl-4-sulfonyl-4H-isoquinoline-1,3-diones was prepared. Members of this series are potent and selective inhibitors of cyclooxygenase-2 (COX-2) in both microsomal and cellular assays. Two representatives demonstrated activity in the carrageenan-induced paw edema model in rats upon oral administration.

  7. Synthesis and antimicrobial activities of novel 1,2,4-triazolo [3,4-a] phthalazine derivatives.

    PubMed

    Zhang, Qiu-Rong; Xue, Deng-Qi; He, Peng; Shao, Kun-Peng; Chen, Peng-Ju; Gu, Yi-Fei; Ren, Jing-Li; Shan, Li-Hong; Liu, Hong-Min

    2014-02-15

    A series of novel 1,2,4-triazolo [3,4-a] phthalazine derivatives were synthesized in five steps from a common precursor, phthalic anhydride. Most of synthesized phthalazine derivatives showed inhibitory activity against Staphylococcus aureus. One of phthalazine derivatives 5l showed inhibitory activity against all tested bacterial and fungal strains.

  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. 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).

  10. 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.

  11. Synthesis, Urease Inhibition, Antioxidant, Antibacterial, and Molecular Docking Studies of 1,3,4-Oxadiazole Derivatives

    PubMed Central

    Hanif, Muhammad; Shoaib, Khurram; Saleem, Muhammad; Hasan Rama, Nasim; Zaib, Sumera; Iqbal, Jamshed

    2012-01-01

    A series of eighteen 1,3,4-oxadiazole derivatives have been synthesized by treating aromatic acid hydrazides with carbon disulfide in ethanolic potassium hydroxide yielding potassium salts of 1,3,4-oxadiazoles. Upon neutralization with 1 N hydrochloric acid yielded crude crystals of 1,3,4-oxadiazoles, which were purified by recrystallization in boiling methanol. The synthesized 1,3,4-oxadiazoles derivatives were evaluated in vitro for their urease inhibitory activities, most of the investigated compounds were potent inhibitors of Jack bean urease. The molecular docking studies were performed by docking them into the crystal structure of Jack bean urease to observe the mode of interaction of synthesized compounds. The synthesized compounds were also tested for antibacterial and antioxidant activities and some derivatives exhibited very promising results. PMID:22934191

  12. 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).

  13. 4-[(E)-(4-Hy­droxy­benzyl­idene)amino]-3-methyl-1H-1,2,4-triazole-5(4H)-thione

    PubMed Central

    Sarojini, Balladka K.; Manjula, Padmanabha S.; Narayana, B.; Jasinski, Jerry P.

    2014-01-01

    The title compound, C10H10N4OS, is nearly planar with the mean planes of the hy­droxy­benzyl and triazole rings inclined at an angle of only 3.2 (7)°. In the crystal, O—H⋯N hydrogen bonds between the hy­droxy group and the triazole ring in concert with weak N—H⋯S inter­molecular inter­actions between the triazole ring and thione group form chains along [-210] enclosing R 2 2(8) graph-set motifs. A weak intra­molecular C—H⋯S inter­action and inter­molecular π–π inter­actions [centroid–centroid distance = 3.5990 (15) Å] are also observed. PMID:24940299

  14. Interactions of antagonists with subtypes of inositol 1,4,5-trisphosphate (IP3) receptor

    PubMed Central

    Saleem, Huma; Tovey, Stephen C; Molinski, Tedeusz F; Taylor, Colin W

    2014-01-01

    BACKGROUND AND PURPOSE Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca2+ channels. Interactions of the commonly used antagonists of IP3Rs with IP3R subtypes are poorly understood. EXPERIMENTAL APPROACH IP3-evoked Ca2+ release from permeabilized DT40 cells stably expressing single subtypes of mammalian IP3R was measured using a luminal Ca2+ indicator. The effects of commonly used antagonists on IP3-evoked Ca2+ release and 3H-IP3 binding were characterized. KEY RESULTS Functional analyses showed that heparin was a competitive antagonist of all IP3R subtypes with different affinities for each (IP3R3 > IP3R1 ≥ IP3R2). This sequence did not match the affinities for heparin binding to the isolated N-terminal from each IP3R subtype. 2-aminoethoxydiphenyl borate (2-APB) and high concentrations of caffeine selectively inhibited IP3R1 without affecting IP3 binding. Neither Xestospongin C nor Xestospongin D effectively inhibited IP3-evoked Ca2+ release via any IP3R subtype. CONCLUSIONS AND IMPLICATIONS Heparin competes with IP3, but its access to the IP3-binding core is substantially hindered by additional IP3R residues. These interactions may contribute to its modest selectivity for IP3R3. Practicable concentrations of caffeine and 2-APB inhibit only IP3R1. Xestospongins do not appear to be effective antagonists of IP3Rs. PMID:24628114

  15. 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).

  16. 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...

  17. Synthesis and Docking Analysis of New Heterocyclic System N1, N4-bis (2-chloroquinolin-3-yl) methylene) benzene-1, 4-diamine as Potential Human AKT1 Inhibitor

    PubMed Central

    Ghanei, Sohrab; Lari, Jalil; Eshghi, Hossein; Saadatmandzadeh, Mohammad

    2016-01-01

    In recent years, the chemistry of 2-chloroquinoline-3-carbaldehydes have received considerable attention owing to their synthetic and effective biological importance which exhibits a wide variety of biological activity, N1,N4-bis((2-chloroquinolin-3-yl)methylene)benzene-1,4-diamine derivatives that synthesized from 2-chloroquinoline-3-carbaldehydes may have biological effects. As the inhibitor of AKT1 (RAC-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1), the aforementioned compounds may have implication in preventing complications of cancers. A group of N1, N4-bis ((2-chloroquinolin-3-yl) methylene) benzene-1, 4-diamine derivatives (3a-3i) (H, 6-Me, 6-OMe, 6-OEt, 6-Cl, 7-Me, 6-Et, 6-Isopropyl, 7-Cl) were synthesized, and theoretically evaluated for their inhibitory as Potential Human AKT1 Inhibitors via docking process. The docking calculation was done in GOLD 5.2.2 software using Genetic algorithm. Compounds 3b (6-Me) and 3d (6-OEt) showed the best inhibitory potency by GOLD score value of 113.76 and 107.58 respectively. Some of the best models formed strong hydrogen bonds with Asn 49, Lys 220, Ser 157, Arg 225 and Trp 76 via quinoline moiety and nitrogen of quinolone ring (Figure 1.). pi-pi interaction between Lys 220, Trp 76, Tyr 224, Arg 225, Ile 80, and Asn 49 quinoline moiety was one of the common factor in enzyme-inhibitor junction. It was found that both hydrogen bonding and hydrophobic interactions are important in function of biological molecules, especially for inhibition in a complex. PMID:27980566

  18. Synthesis, properties, and redox behavior of 1,1,4,4-tetracyano-2-ferrocenyl-1,3-butadienes connected by aryl, biaryl, and teraryl spacers.

    PubMed

    Shoji, Taku; Maruyama, Akifumi; Yaku, Chisa; Kamata, Natsumi; Ito, Shunji; Okujima, Tetsuo; Toyota, Kozo

    2015-01-02

    Aryl-substituted 1,1,4,4-tetracyano-1,3-butadienes (FcTCBDs) and bis(1,1,4,4-tetracyanobutadiene)s (bis-FcTCBDs), possessing a ferrocenyl group on each terminal, were prepared by the reaction of a variety of alkynes with tetracyanoethylene (TCNE) in a [2+2] cycloaddition reaction, followed by retro-electrocyclization of the initially formed [2+2] cycloadducts (i.e., cyclobutene derivatives). The characteristic intramolecular charge transfer (ICT) between the donor (ferrocene) and acceptor (TCBD) moieties were investigated by using UV/Vis spectroscopy. The redox behaviors of FcTCBDs and bis-FcTCBDs were examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV), which revealed their properties of multi-electron transfer depending on the number of ferrocene and TCBD moieties. Moreover, significant color changes were observed by visible spectroscopy under the electrochemical reduction conditions.

  19. Trimethylation of histone H3 lysine 4 by Set1 in the lytic infection of human herpes simplex virus 1.

    PubMed

    Huang, Jing; Kent, Jennifer R; Placek, Brandon; Whelan, Kelly A; Hollow, Charles M; Zeng, Ping-Yao; Fraser, Nigel W; Berger, Shelley L

    2006-06-01

    Human herpes simplex virus 1 (HSV-1) is a double-stranded DNA virus that causes facial, ocular, and encephalitic disease in humans. Previous work showed that the genome of HSV-1 is associated with acetylated and methylated histones during lytic infection. However, the physiological role of histone modifications in lytic infection of HSV-1 is unclear. We examined the role of protein methylation in lytic infection of HSV-1 using a protein methylation inhibitor, 5'-deoxy-5'-methylthioadenosine (MTA). We found that MTA strongly reduces the transcription and replication of HSV-1. Moreover, MTA treatment decreases the level of trimethylation of lysine 4 in histone H3 (H3K4me3) on the HSV-1 genome. These results suggest that protein methylation, and in particular, histone methylation, is involved in the lytic infection of HSV-1. To delineate the underlying mechanism, we investigated the role of two H3K4 methyltransferases, Set1 and Set7/9, in the lytic infection of HSV-1. Using small interference RNA, we found that the reduction of Set1, but not Set7/9, reduces the transcription and replication of HSV-1 and specifically decreases H3K4me3 on the virus genome. These results indicate that H3K4me3 mediated by Set1 is required for optimal gene expression and replication of HSV-1 during lytic infection and suggest that this pathway could be a potential point of pharmacological intervention during HSV-1 infection.

  20. Discovery of Benzotriazolo[4,3-d][1,4]diazepines as Orally Active Inhibitors of BET Bromodomains

    PubMed Central

    2015-01-01

    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

  1. 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.

  2. A convenient synthesis of 6-amino-1-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4-one and related 4,6-disubstituted pyrazolopyrimidine nucleosides.

    PubMed Central

    Cottam, H B; Revankar, G R; Robins, R K

    1983-01-01

    The glycosylation of 4,6-dichloropyrazolo[3,4-d]pyrimidine and 4-chloro-6-methylthiopyrazolo[3,4-d]pyrimidine via the corresponding trimethylsilyl intermediate and tetra-O-acetyl-beta-D-ribofuranose in the presence of trimethylsilyl triflate as a catalyst, gave selective glycosylation at N1 as the only nucleoside product. The intermediates 4,6-dichloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo [3,4-d]pyrimidine 7 and 4-chloro-6-methylthio-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo [3,4-d]pyrimidine 13 gave new and convenient synthetic routes to the inosine analog 1, the guanosine analog 2, the adenosine analog 3, and the isoguanosine analog 16. Glycosylation of the trimethylsilyl derivative of 6-chloropyrazolo[3,4-d]pyrimidine-4-one unexpectedly gave the N2-glycosyl isomer 20 as the major product. A number of new 4,6-disubstituted pyrazolo[3,4-d]pyrimidine nucleosides were prepared from these glycosyl intermediates. PMID:6835838

  3. Reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithiethane with N-vinyl compounds.

    PubMed

    Petrov, Viacheslav A; Marshall, Will

    2013-01-01

    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.

  4. Studies on molecular structure, vibrational spectra and molecular docking analysis of 3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl 4-aminobenzoate.

    PubMed

    Suresh, D M; Amalanathan, M; Joe, I Hubert; Jothy, V Bena; Diao, Yun-Peng

    2014-09-15

    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.

  5. 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.

  6. Synthesis and evaluation of benzosuberone embedded with 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole moieties as new potential anti proliferative agents.

    PubMed

    Yadagiri, Bandi; Gurrala, Srikanth; Bantu, Rajashaker; Nagarapu, Lingaiah; Polepalli, Sowjanya; Srujana, Garimella; Jain, Nishant

    2015-01-01

    As an aspect of our ongoing research in search of new anti proliferative agents, a series of novel analogs of benzosuberone embedded with 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole moieties were synthesized in excellent yields (82-93%). All the newly synthesized compounds were characterized by (1)H NMR, (13)C NMR, ESI/LC-MS, HRMS and evaluated for their in vitro anti proliferative activity against four human cancer cell lines (cervical, breast, pancreatic and alveolar). Among the synthesized compounds, 4b, 6a, 7d and 7l showed potent anti proliferative activity with GI50 values range of 0.079-0.957μM against four human cancer cell lines. However, it was revealed that the compound 7d have shown very close GI50 value 0.079μM as compared with positive control of colchicine against cervical cancer cell line.

  7. Synthesis of some new 1,2,4-triazole derivatives starting from 3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol with anti-lipase and anti-urease activities.

    PubMed

    Bekircan, Olcay; Menteşe, Emre; Ulker, Serdar; Kucuk, Cagatay

    2014-06-01

    In the present study, starting compound 4 was prepared by deamination of compound 2 in the presence of hypophosphorous acid and sodium nitrite. Treatment of compound 4 with ethyl bromoacetate produced ethyl[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetate (5), which was converted to the hydrazide derivative (6) by treatment with hydrazine hydrate. The reaction of compound 6 with aromatic aldehydes resulted in the formation of arylidene hydrazides (7). Treatment of 6 with CS2 in the presence of potassium hydroxide (KOH), followed by cyclization with hydrazine hydrate, afforded 4-amino-5-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione (9). The condensation of 9 with appropriate aldehydes gave Schiff bases (10), which were converted into Mannich bases (11) in the presence of formaldehyde. All the synthesized compounds were screened for their anti-lipase and anti-urease activities. Compounds 7b, 7d, 11b, 11c, and 11d showed moderate-to-good lipase inhibitory effects compared to orlistat. Compounds 7b and 7d exhibited better anti-lipase activity. Furthermore, among the compounds tested, 11a and 11d were found to show high inhibitory effect against urease with IC50 values of 12.39 ± 0.35 and 16.12 ± 1.06 µg/mL, respectively. Compound 11c showed moderate inhibitory activity. The Mannich base containing compound 11 may be a source of good leads for the synthesis of lipase and urease dual inhibitors.

  8. N-(2,3-Dihydro-1,4-benzodioxin-6-yl)-4-fluoro-benzene-sulfonamide.

    PubMed

    Mughal, Shumaila Younas; Khan, Islam Ullah; Harrison, William T A; Khan, Muneeb Hayat; Arshad, Muhammad Nadeem

    2012-08-01

    In the title compound, C(14)H(12)FNO(4)S, the dihedral angle between the aromatic rings is 50.26 (9)° and the C-S-N-C bond adopts a gauche conformation [torsion angle = -68.12 (15)°]. The dihydro-dioxine ring is disordered over two orientations, which both approximate to half-chairs, in a 0.880 (7):0.120 (7) ratio. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into C(4) chains propagating in [100]. Weak C-H⋯O and C-H⋯F inter-actions consolidate the packing.

  9. 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.

  10. DNA strand scission by the nephrotoxin [2,2'-bipyridine]-3,3',4,4'-tetrol-1,1'-dioxide and related compounds in the presence of iron.

    PubMed

    Cantin-Esnault, D; Oubrahim, H; Richard, J M

    2000-08-01

    The capacity of non-illuminated nephrotoxin orellanine ([2,2'-bipyridine]-3,3',4,4'-tetrol-1,1'-dioxide) to induce DNA damage in the presence of ferrous iron and dioxygen has been evaluated. Maximal single-strand breaks in plasmid DNA were obtained with a metal to ligand ratio 1:3. Instantaneous oxidation of Fe2+ in presence of orellanine under air was responsible for oxy-radical production concomitant to a stable ferric complex Fe(III)Or3 formation, leading to oxidative DNA breakage at physiological pH. DNA damage was lowered in the presence of SOD and catalase or DMSO, indicating a set of reactions that leads to oxy-radical generation. Iron chelators such as DTPA and EDTA had no protecting effect, Desferal slightly protected. GSH acted as an oxy-radical scavenger, whereas cysteine induced stronger damage. Closely related bipyridine compounds were also studied in presence of Fe2+ and O2 using a combination of spin-trapping and DNA-nicking experiments, none of which were able to chelate iron and induce damage at pH 7. Both catecholic moieties and aminoxide groups are required for observing breakage at physiological pH.

  11. Exendin-4 promotes proliferation and differentiation of MC3T3-E1 osteoblasts by MAPKs activation.

    PubMed

    Feng, Yingyu; Su, Lei; Zhong, Xing; Guohong, Wei; Xiao, Haipeng; Li, Yanbing; Xiu, Lingling

    2016-04-01

    Glucagon-like peptide-1 (GLP1) and its receptor agonist have been previously reported to play a positive role in bone metabolism in aged ovariectomized rats and insulin-resistant models. However, whether GLP1 has a direct effect on the proliferation and differentiation of osteoblasts or any cellular mechanism for this potential role is unknown. We examined the effects of the GLP1 receptor agonist exendin-4 on the proliferation, differentiation, and mineralization of mouse osteoblastic MC3T3-E1 cells. GLP1 receptor was detected in MC3T3-E1 cells by polymerase chain reaction (PCR) and Western blot assay. Cell proliferation was assessed using MTT assay, revealing that exendin-4 increased cell proliferation at effective concentrations between 10(-10) and 10(-5) M. Quantitative PCR analysis showed that exendin-4 increased the mRNA expression of the differentiation markers alkaline phosphatase (ALP), collagen-1 (COL1), osteocalcin (OC), and runt-related transcription factor 2 (RUNX2) under osteogenic conditions. Alizarin red staining confirmed that 10(-7) M exendin-4 increased osteoblast mineralization by 18.7%. Exendin-4 upregulated the phosphorylation of ERK1/2, p38, and JNK, with the peak effect at 1.5 h in the Western blot analysis. The use of selective MAPK inhibitors, namely PD98059, SB203580, and SP600125, blocked the effects of exendin-4 on kinase activation (ERK1/2, p38, and JNK), as well as cell proliferation and differentiation in MC3T3-E1 cells. These findings demonstrate that exendin-4 promotes both the proliferation and differentiation of preosteoblasts MC3T3-E1 via activation of the MAPK pathway.

  12. 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

  13. Novel pyrazole integrated 1,3,4-oxadiazoles: synthesis, characterization and antimicrobial evaluation.

    PubMed

    Ningaiah, Srikantamurthy; Bhadraiah, Umesha K; Doddaramappa, Shridevi D; Keshavamurthy, Shubakara; Javarasetty, Chethan

    2014-01-01

    A novel series of 2-(5-methyl-1,3-diphenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazoles 7(a-m) were synthesized either by cyclization of N'-benzoyl-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 4a using POCl3 at 120°C or by oxidative cyclization of hydrazones derived from various arylaldehyde and (E)-N'-benzylidene-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 5(a-d) using chloramine-T as oxidant. Newly synthesized compounds were characterized by analytical and spectral (IR, (1)H NMR, (13)C NMR and LC-MS) methods. The synthesized compounds were evaluated for their antimicrobial activity and were compared with standard drugs. The compounds demonstrated potent to weak antimicrobial activity. Among the synthesized compounds, compound 7m emerged as an effective antimicrobial agent, while compounds 7d, 7f, 7i and 7l showed good to moderate activity. The minimum inhibitory concentration of the compounds was in the range of 20-50μgmL(-1) against bacteria and 25-55μgmL(-1) against fungi. The title compounds represent a novel class of potent antimicrobial agents.

  14. 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...

  15. DFT study on energetic tetrazolo-[1,5-b]-1,2,4,5-tetrazine and 1,2,4-triazolo-[4,3-b]-1,2,4,5-tetrazine derivatives.

    PubMed

    Wei, Tao; Zhu, Weihua; Zhang, Jingjing; Xiao, Heming

    2010-07-15

    The heats of formation (HOFs) for a series of tetrazolo-[1,5-b]-1,2,4,5-tetrazine (TETZ) and 1,2,4-triazolo-[4,3-b]-1,2,4,5-tetrazine (TTZ) derivatives were studied by using density functional theory. The results show that the substitution of the -N(3) or -N(NO(2))(2) group in the TETZ or TTZ ring extremely enhances its HOF values. For monosubstituted case, attachment of a substituent to position 8 in the TETZ or TTZ ring will increase its energy gaps except for the derivatives with the -NO(2) group. It is also found that the energy gap of TTZ can be tuned by incorporating a substituent into different positions in the parent ring. The substitution of the -NH(2) group in the TETZ ring is favorable for enhancing its thermal stability. For the TTZ ring, different substituted positions and number of the substituent might affect its thermal stability. The calculated detonation properties indicate that incorporating the -NO(2), -NF(2), -ONO(2), or -N(NO(2))(2) group into the TETZ or TTZ ring is very helpful for enhancing its detonation performance. Considered the detonation performance and thermal stability, four derivatives may be regarded as the promising candidates of high-energy density materials (HEDMs).

  16. [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.

  17. (E)-4-(1,3-Benzodioxol-5-yl)but-3-en-2-one

    PubMed Central

    Sarveswari, S.; Vijayakumar, V.; Mathew, Priya Susan; Mendoza-Meroño, Rafael; García-Granda, Santiago

    2011-01-01

    In the title compound, C11H10O3, the benzodioxole ring adopts a flattened [puckering parameters: q 2 = 0.107 (2) Å, ϕ2 = 160 (1)°] envelope conformation with the methylene C atom as the flap. The crystal packing features chains, parallel to the c axis, composed of dimers connected by weak C—H–O hydrogen bonds and extending in layers in the bc plane. PMID:21522344

  18. Reaction of 1Н,2Н,3Н,4Н-pyrido[4,3-d]pyrimidinium bromide derivatives with molecular iodine: Comparative structure and spectroscopic analysis

    NASA Astrophysics Data System (ADS)

    Chernov'yants, Margarita S.; Burykin, Igor V.; Kostrub, Vladimir V.; Tsupak, Evgeny B.; Starikova, Zoya A.; Kirsanova, Julia A.

    2012-02-01

    New salts C27H22N3O2BrI2 (1) and C27H19N3O2Br4I2·2CHCl3·2H2O (2) were synthesized by the iodination of derivatives of 1,3-dimethyl-2,4-dioxo-5,6,7-R-1Н,2Н,3Н,4Н-pyrido[4,3-d]pyrimidinium bromide (R = phenyl (1a), p-bromphenyl (2a)) with an equimolar amount of iodine. The positive values of enthalpy (ΔH) and entropy (ΔS) indicate that the complexation of organic bromide and iodine molecule in chloroform solution is mainly entropically driven. The molecular and crystal structures (1) and (2) are studied by X-ray diffraction analysis. The structure of diiodinebromide 1 is composed of separate almost liner BrI2- and 1,3-dimethyl-2,4-dioxo-5,6,7-thriphenyl-1Н,2Н,3Н,4Н-pyrido[4,3-d]pyrimidinium cation. The crystal structure 2 is built up of alternate layers of (CHNOBr3+)(I3-) (A) and (Br2I-)(СHСl3) (B), connected to each other by hydrogen bonds Br(BrI)⋯H(CHNOBr3+). The formation of the ions I3- and Br2I- occurs via the disproportionation of I2Br- under the action of solvent on C27H19N3O2Br4I2·2CHCl3·2H2O (2) crystallization.

  19. Reconstruction phase transition c(4×4) - (1×3) on the (001)InSb surface

    NASA Astrophysics Data System (ADS)

    Bakarov, A.; Galitsyn, Yu.; Mansurov, V.; Zhuravlev, K.

    2017-01-01

    The (001) surface of InSb is the most common growth surface, forming a number of surface reconstructions depending on the both ratio of group III and V species presented on surface and substrate temperature. In the present work surface structures were studied using reflection high energy electron diffraction (RHEED). The c(4×4)↔(1×3) reconstruction transition was investigated in details. The intensity of fractional spots of c(4×4) structure was measured during the variation of antimony flux at different substrate temperatures. At the substrate temperatures of T<400 °C, hysteresis loop of fractional spot intensity appeared during the forward and reverse Sb flux variation, testifying that c(4×4)↔(1×3) transition is discontinuous first order phase transition. At the temperatures T>400 °C, hysteresis loop was not observed, that corresponds to continuous phase transition. It was shown that phase transition is analogous to the van der Waals transition. We developed a model to describe c(4×4)↔(1×3) transition in the framework of the lattice gas approximation. This model takes into account the complex nature of indirect interactions that result in the effective attraction between lattice gas cells forming surface reconstruction. The calculated surface state isotherms are in a good agreement with the experimental isotherms.

  20. Supramolecular hydrogen-bonded 1D arrangement in the crystals of 2,4-diamino-6-benzyl-1,3,5-triazine and 2,4-diamino-6-(4‧-methylbenzyl)-1,3,5-triazine

    NASA Astrophysics Data System (ADS)

    Janczak, Jan; Kubiak, Ryszard

    2009-02-01

    Two crystals of triazine derivatives, 2,4-diamino-6-benzyl-1,3,5-triazine ( 1) and 2,4-diamino-6-(4'-methylbenzyl)-1,3,5-triazine ( 2), are synthesised by a direct reaction of cyanoguanidine with the respective cyanocompounds. The IR spectra of the compounds are very similar. In the crystals the molecules are interconnected by N sbnd H⋯N hydrogen bonds forming one-dimensional hydrogen bonded polymer in 1 and three-dimensional hydrogen bonded network in 2. The arrangement of molecules in the crystal of 1 is denser than in 2 due to the π-π interactions between the π-clouds of the aromatic triazine rings that are absent in the crystal of 2. The geometries of the molecules in the crystals have been compared with those obtained by ab-initio molecular orbital calculated results that represent the geometries of molecules in the gas-phase.

  1. Structural, conformational and pharmacological study of some esters derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9β-ol

    NASA Astrophysics Data System (ADS)

    Iriepa, I.; Gil-Alberdi, B.; Gálvez, E.; Sanz-Aparicio, J.; Fonseca, I.; Orjales, A.; Berisa, A.; Labeaga, C.

    1995-06-01

    A series of some esters derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9β-ol were synthesized and studied by 1H and 13C NMR spectroscopy, and the crystal structure of 3-methyl-2,4-diphenyl-9β(3,5-dimethyl-benzoyloxy)-3-azabicyclo[3.3.1]nonane ( II) has been determined by X-ray diffraction. The compounds studied display, in deuterochloroform, a flattened chair-chair conformation with the cyclohexane ring more flattened than the piperidine moiety and the NCH 3 groups in equatorial position. Pharmacological assays on mices were drawn to evaluate drug-induced behavioral alteration, peripheral or central acute toxicity analgesic and neuroleptic activity.

  2. Interaction between ANXA1 and GATA-3 in Immunosuppression of CD4+ T Cells

    PubMed Central

    Huang, Peng; Zhou, Yuxiang; Liu, Zan

    2016-01-01

    Decreased Th1/Th2 ratio is one of the major characteristics of immunosuppression in sepsis. Both membrane adhesive protein Annexin-A1 (ANXA1) and transcription factor GATA-3 have been reported to play important roles in T cell differentiation. However, the relationship between ANXA1 and GATA-3 in Th1/Th2 shift is unknown. Our study investigated the interaction effects of ANXA1 and GATA-3 to influence T cell differentiation in CD4+ T cells. We found that GATA-3 and ANXA1 were coexpressed on Th0/Th1/Th2 cytoplasm and nuclear. Overexpressed ANXA1 significantly increased the expression of IFNγ and reduced IL-4 expression in T cells, while ANXA1-silenced T cells exhibited decreased production of IFNγ and increased production of IL-4. Knockdown of ANXA1 promoted higher expression level of GATA-3 and low level of T-box transcription factor (T-bet/Tbx21). Further study demonstrated that ANXA1 regulated GATA-3 expression through the formyl peptide receptor like-1 (FPRL-1) downstream signaling pathways ERK and PKB/Akt. These results suggested that ANXA1 modulates GATA-3/T-bet expression induced Th0/Th1 differentiation. Moreover, we found that GATA-3 inhibited ANXA1 expression by binding to its promoter for the first time. It is proposed that the interactions between ANXA1 and GATA-3 may provide clues to understand the immunosuppression and have potential as new therapeutic targets in immunotherapy after sepsis. PMID:27833268

  3. 3-(Piperidin-4-ylmethoxy)pyridine Containing Compounds Are Potent Inhibitors of Lysine Specific Demethylase 1

    PubMed Central

    Yao, Yuan; Wei, Liping; Feng, Zizhen; Deng, Lisheng; Song, Yongcheng

    2016-01-01

    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

  4. (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

  5. [Bis((2,4-dioxo-1,2,3,4-tetrahydroquinazolin-3-yl)alkyl)disulfane and 3-(mercaptoalkyl)quinazolin-2,4(1H,3H)-dione: synthesis by ring transformation and antiviral activity. 42. Heterocyclic azines with heteroatoms in the 1- and 3- positions].

    PubMed

    Gütschow, M; Tonew, E; Leistner, S

    1995-10-01

    Reaction of N-(sulfonyloxy)phtalimide derivatives 1, 2, with cystamine and homocystamine, respectively, affords bis[2,4-dioxol-1,2,3,4-tetra-hydroquinazolin-3-yl)alkyl] disulfanes [sequence: see text] 3, which could be reduced to 3-(mercaptoalkyl)quinazoline-2,4(1H,3H)-diones. 5. (3-(2-Mercaptoethyl)quinazoline-2,4(1H,3H)-dione (5a) was also obtained in a one-pot reaction from 1 or 2 and cysteamine. 2-Ethoxy-4H-3,1-benzoxazin-4-ones 4a-c were converted with cysteamine to 3-(mercaptoethyl)quinazoline-2,4-diones 5a-c by a new ringtransformation reaction. 3-(2-Mercaptoethyl)quinazoline-2,4(1H,3H)dione (5a) and the corresponding disulfane 3a were evaluated for antiviral activity in vitro. Compounds 3a and 5a showed significant antiviral activity against some DNA- and RNA-viruses (vaccinia-, herpes simplex virus type 1; influenza A virus) at concentrations that were nontoxic to the host cell cultures.

  6. Urethral carcinoma and hyperplasia in male and female B6C3F1 mice treated with 3,3′,4,4′- Tetrachloroazobenzene (TCAB)

    PubMed Central

    Singh, BP; Nyska, A; Kissling, GE; Lieuallen, W; Johansson, SL; Malarkey, DE; Hooth, MJ

    2010-01-01

    B6C3F1 mice chronically exposed to 3,3′,4,4′-tetrachloroazobenzene (TCAB), a contaminant of dichloroaniline-derived herbicides, developed a number of neoplastic and nonneoplastic lesions including carcinoma of the urinary tract. Groups of 50 male and 50 female B6C3F1 mice were exposed by gavage to TCAB at dose levels of 0, 3, 10 and 30 mg/kg 5 days a week for 2 years. Control animals received corn oil:acetone (99:1) vehicle. Decreased survival of male mice in the mid-dose group and of male and female mice in the high dose groups was mainly related to the occurrence of urethral transitional cell (urothelial) carcinoma and resulting urinary obstruction. Increased urethral transitional cell carcinomas were seen in all treated male groups in a dose-related manner as well as in the females treated with 30 mg/kg TCAB. Administration of TCAB was also associated with increased transitional cell hyperplasia of the urethra. Most nonneoplastic lesions of the urogenital tract were considered secondary to local invasion and urinary obstruction by the urethral transitional cell carcinomas. The mechanism of tumor induction is uncertain but the high frequency of tumors in the proximal urethra of male mice suggests that the neoplasms result from the exposure of a susceptible population of urothelial cells to a carcinogenic metabolite of TCAB. PMID:20233943

  7. Synthesis and evaluation of 3-[(2,4-dioxo-1,3,8-triazaspiro[4.6]undec-3-yl)methyl]benzonitrile derivatives as potential anticonvulsants.

    PubMed

    Madaiah, Malavalli; Prashanth, Maralekere K; Revanasiddappa, Hosakere D; Veeresh, Bantal

    2013-03-01

    New 3-[(2,4-dioxo-1,3,8-triazaspiro[4.6]undec-3-yl)methyl]benzonitrile derivatives 8-37 were synthesized and their pharmacological activities were determined with the objective to better understand their structure-activity relationship (SAR) for anticonvulsant activity. All the compounds were evaluated for their possible anticonvulsant activity by maximal electroshock seizure (MES) and pentylenetetrazole (PTZ) test. Compounds 11, 18, 31, and 32 showed significant and protective effect on seizure, when compared with the standard drug valproate. The same compounds were found to exhibit advanced anticonvulsant activity as well as lower neurotoxicity than the reference drug. From this study, it is quite apparent that there are at least three parameters for the activity of anticonvulsant drugs, that is, a lipophilic domain, a hydrophobic center, and a two-electron donor.

  8. Synthesis and characterization of some novel 1,2,4-triazoles, 1,3,4-thiadiazoles and Schiff bases incorporating imidazole moiety as potential antimicrobial agents.

    PubMed

    Aouad, Mohamed Reda; Messali, Mouslim; Rezki, Nadjet; Ali, Adeeb Al-Sheikh; Lesimple, Alain

    2015-06-01

    (1,4,5-Triphenylimidazol-2-yl-thio)butyric acid hydrazide (3) was obtained via alkylation of 1,4,5-triphenylimidazol-2- thiol (1) with ethylbromobutyrate, followed by addition of hydrazine hydrate. Treatment of acid hydrazide 3 with carbon disulfide in an ethanolic potassium hydroxide solution gave the intermediate potassium dithiocarbazinate salt, which was cyclized to 4-amino-5-[(1,4,5-triphenylimidazol- -2-yl)thiopropyl]-2H-1,2,4-triazole-3-thione (4) in the presence of hydrazine hydrate. Condensation of compound 3 with alkyl/arylisothiocyanate afforded the corresponding 1-[4-(1,4,5-triphenylimidazol-2-ylthio)butanoyl]-4-alkyl/arylthiosemicarbazides (5-7), which upon refluxing with sodium hydroxide, yielded the corresponding 1,2,4-triazole - -3-thiols 8-10. Under acidic conditions, compounds 4-6 were converted to aminothiadiazoles 11-13. Moreover, the series of Schiff bases 14-18 were synthesized from the condensation of compound 3 with different aromatic aldehydes. The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and mass spectral analyses. They were also preliminarily screened for their antimicrobial activity.

  9. 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.

  10. Volumetric Properties of the Mixture (+,-)-Methyl-1,3-dioxolan-2-one C4H6O3 + C6H12O3 2,4,6-Trimethyl-1,3,5-trioxane (VMSD1511, LB4523_V)

    NASA Astrophysics Data System (ADS)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture (+,-)-Methyl-1,3-dioxolan-2-one C4H6O3 + C6H12O3 2,4,6-Trimethyl-1,3,5-trioxane (VMSD1511, LB4523_V)' providing data from direct measurement of low-pressure thermodynamic speed of sound at variable mole fraction and constant temperature, in the single-phase region(s).

  11. Synthesis of 7-azabicyclo[2.2.1]heptane and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives by base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides.

    PubMed

    Gómez-Sanchez, Elena; Soriano, Elena; Marco-Contelles, José

    2007-11-09

    We have studied the base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides, investigating the effect of the nitrogen protecting group and the relative configuration of the leaving group at C3 and C4 on the outcome of this reaction. We have observed that the sodium hydride-promoted heterocyclization of alkyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamates (10, 12, 14, 16, 18) is a convenient method for the synthesis of 7-azabicyclo[2.2.1]heptane derivatives. For instance, the reaction of tert-butyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamate (10) with sodium hydride in DMF at room temperature provides 2-bromo-7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]heptane (2) (52% yield), whose t-BuOK-promoted hydrogen bromide elimination affords 7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]hept-2-ene (31) in 78% yield, an intermediate in the total synthesis of epibatidine (1). However, the NaH/DMF-mediated heterocyclization of alkyl N-(trans-3,cis-4-dibromocyclohex-1-yl)carbamates (11, 13) is a more structure dependent reaction, where the nucleophilic attack of the oxygen atom of the protecting group controls the outcome of the reaction, giving rise to benzooxazolone and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, from low to moderate yields, in complex reaction mixtures. Conversely, the NaH/DMF heterocyclizations of N-(cis-3,trans-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (40) or N-(trans-3,cis-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (42) are very clean reactions giving 7-azabicyclo[2.2.1]heptane or 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, in good yields. Finally, a mechanistic investigation, based on DFT calculations, has been carried out to rationalize the formation of the different adducts.

  12. A food-grade industrial arming yeast expressing beta-1,3-1,4-glucanase with enhanced thermal stability.

    PubMed

    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 beta-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 beta-1,3-1,4-glucanase gene from Bacillus subtilis was fused to alpha-agglutinin and expressed under the control of the GAL1 promoter. alpha-galactosidase induced by the constitutive PGK1 promoter was used as a food-grade selection marker. The feasibility of the alpha-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 beta-1,3-1,4-glucanase. The analysis of beta-1,3-1,4-glucanase activity in cell pellets and in the supernatant of the recombinant yeast strain revealed that beta-1,3-1,4-glucanase was successfully displayed on the cell surface of the yeast. The displayed beta-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 beta-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.

  13. 4-Quinolone-3-carboxylic acids as cell-permeable inhibitors of protein tyrosine phosphatase 1B.

    PubMed

    Zhi, Ying; Gao, Li-Xin; Jin, Yi; Tang, Chun-Lan; Li, Jing-Ya; Li, Jia; Long, Ya-Qiu

    2014-07-15

    Protein tyrosine phosphatase 1B is a negative regulator in the insulin and leptin signaling pathways, and has emerged as an attractive target for the treatment of type 2 diabetes and obesity. However, the essential pharmacophore of charged phosphotyrosine or its mimetic confer low selectivity and poor cell permeability. Starting from our previously reported aryl diketoacid-based PTP1B inhibitors, a drug-like scaffold of 4-quinolone-3-carboxylic acid was introduced for the first time as a novel surrogate of phosphotyrosine. An optimal combination of hydrophobic groups installed at C-6, N-1 and C-3 positions of the quinolone motif afforded potent PTP1B inhibitors with low micromolar IC50 values. These 4-quinolone-3-carboxylate based PTP1B inhibitors displayed a 2-10 fold selectivity over a panel of PTP's. Furthermore, the bidentate inhibitors of 4-quinolone-3-carboxylic acids conjugated with aryl diketoacid or salicylic acid were cell permeable and enhanced insulin signaling in CHO/hIR cells. The kinetic studies and molecular modeling suggest that the 4-quinolone-3-carboxylates act as competitive inhibitors by binding to the PTP1B active site in the WPD loop closed conformation. Taken together, our study shows that the 4-quinolone-3-carboxylic acid derivatives exhibit improved pharmacological properties over previously described PTB1B inhibitors and warrant further preclinical studies.

  14. Helicase CHD4 is an epigenetic coregulator of PAX3-FOXO1 in alveolar rhabdomyosarcoma

    PubMed Central

    Böhm, Maria; Marques, Joana G.; Streiff, Natalie; Laubscher, Dominik; Mamchaoui, Kamel; Santoro, Raffaella; Schäfer, Beat W.

    2016-01-01

    A vast number of cancer genes are transcription factors that drive tumorigenesis as oncogenic fusion proteins. Although the direct targeting of transcription factors remains challenging, therapies aimed at oncogenic fusion proteins are attractive as potential treatments for cancer. There is particular interest in targeting the oncogenic PAX3-FOXO1 fusion transcription factor, which induces alveolar rhabdomyosarcoma (aRMS), an aggressive cancer of skeletal muscle cells for which patient outcomes remain dismal. In this work, we have defined the interactome of PAX3-FOXO1 and screened 60 candidate interactors using siRNA-mediated depletion to identify candidates that affect fusion protein activity in aRMS cells. We report that chromodomain helicase DNA binding protein 4 (CHD4), an ATP-dependent chromatin remodeler, acts as crucial coregulator of PAX3-FOXO1 activity. CHD4 interacts with PAX3-FOXO1 via short DNA fragments. Together, they bind to regulatory regions of PAX3-FOXO1 target genes. Gene expression analysis suggested that CHD4 coregulatory activity is essential for a subset of PAX3-FOXO1 target genes. Depletion of CHD4 reduced cell viability of fusion-positive but not of fusion-negative RMS in vitro, which resembled loss of PAX3-FOXO1. It also caused specific regression of fusion-positive xenograft tumors in vivo. Therefore, this work identifies CHD4 as an epigenetic coregulator of PAX3-FOXO1 activity, providing rational evidence for CHD4 as a potential therapeutic target in aRMS. PMID:27760049

  15. Synthesis, structural characterization, and DFT calculations of 3-buthyl-4-(3-methyl-3-mesitylcyclobut-1-yl)-1,3-thiazole-2(3 H)-thione

    NASA Astrophysics Data System (ADS)

    Şen, B.; Barim, E.; Kirilmis, C.; Aygün, M.

    2016-03-01

    The title compound, C21H29NS2, has been synthesized and its crystal structure has been determined from single crystal X-ray diffraction data. Crystals are monoclinic, a = 11.4923(8), b = 13.1842(7), c = 14.6583(8) Å, β = 109.983(6)°, sp. gr. P21/ c, Z = 4. Mesityl and thiazole groups are in cis positions with respect to the cyclobutane ring. The cyclobutane ring is puckered, with a dihedral angle of 26.6(2)° between the two three-atom planes. The crystal structure involves one weak intermolecular C-H···S hydrogen-bond. The molecular geometry was also optimized using density functional theory (DFT/B3LYP) method with the 6-311G( d, p) basis set in ground state. Geometric parameters (bond lengths, bond angles and torsion angles) and vibrational assignments have been calculated theoretically and compared with the experimental data.

  16. Formation of 1,4,2-Dithiazolidines or 1,3-Thiazetidines from 1,1-Dichloro-2-nitroethene and Phenylthiourea Derivatives.

    PubMed

    Feng, Yian; Zou, Minming; Song, Runjiang; Shao, Xusheng; Li, Zhong; Qian, Xuhong

    2016-11-04

    A method for preparation of 1,4,2-dithiazolidine or 1,3-thiazetidine heterocycles was developed by reactions of phenylthioureas with 1,1-dichloro-2-nitroethene. The solvent has a significant influence on the type of product formation. 1,4,2-Dithiazolidines were formed in the aprotic solvent chloroform, while in the protic solvent ethanol, 1,3-thiazetidines were the main products.

  17. Transgenic barley expressing a protein-engineered, thermostable (1,3-1,4)-beta-glucanase during germination.

    PubMed Central

    Jensen, L G; Olsen, O; Kops, O; Wolf, N; Thomsen, K K; von Wettstein, D

    1996-01-01

    The codon usage of a hybrid bacterial gene encoding a thermostable (1,3-1,4)-beta-glucanase was modified to match that of the barley (1,3-1,4)-beta-glucanase isoenzyme EII gene. Both the modified and unmodified bacterial genes were fused to a DNA segment encoding the barley high-pI alpha-amylase signal peptide downstream of the barley (1,3-1,4)-beta-glucanase isoenzyme EII gene promoter. When introduced into barley aleurone protoplasts, the bacterial gene with adapted codon usage directed synthesis of heat stable (1,3-1,4)-beta-glucanase, whereas activity of the heterologous enzyme was not detectable when protoplasts were transfected with the unmodified gene. In a different expression plasmid, the codon modified bacterial gene was cloned downstream of the barley high-pI alpha-amylase gene promoter and signal peptide coding region. This expression cassette was introduced into immature barley embryos together with plasmids carrying the bar and the uidA genes. Green, fertile plants were regenerated and approximately 75% of grains harvested from primary transformants synthesized thermostable (1,3-1,4)-beta-glucanase during germination. All three trans genes were detected in 17 progenies from a homozygous T1 plant. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8622963

  18. Diversity-oriented synthesis of 1-substituted 4-aryl-6-oxo-1,6-dihydropyridine-3-carboxamides.

    PubMed

    Baškovč, Jernej; Dahmann, Georg; Golobič, Amalija; Grošelj, Uroš; Kočar, Drago; Stanovnik, Branko; Svete, Jurij

    2012-09-10

    A simple five-step diversity-oriented synthesis of 1-substituted 4-aryl-6-oxo-1,6-dihydropyridine-3-carboxamides was developed. Treatment of dimethyl 2-((dimethylamino)methylidene)-3-oxopentanedioate with twenty primary amines gave 1-substituted methyl 4-hydroxy-6-oxo-1,6-dihydropyridine-3-carboxylates. Transformation into the corresponding 4-tosyloxy and 4-chloro derivatives, followed by Suzuki-Miyaura arylations gave a series of eleven N-substituted methyl 4-aryl-6-oxo-1,6-dihydropyridine-3-carboxylates. Combinatorial screening was employed to establish suitable reaction conditions for Suzuki-Miyaura arylation of N-alkylpyridones. Hydrolysis of the esters followed by parallel solution-phase amidation of the corresponding carboxylic acids with primary and secondary amines furnished a library of seventeen final products.

  19. Electronic coupling between two cyclometalated ruthenium centers bridged by 1,3,6,8-tetrakis(1-butyl-1H-1,2,3-triazol-4-yl)pyrene.

    PubMed

    Wang, Lei; Yang, Wen-Wen; Zheng, Ren-Hui; Shi, Qiang; Zhong, Yu-Wu; Yao, Jiannian

    2011-08-01

    A new bridging ligand 1,3,6,8-tetrakis(1-butyl-1H-1,2,3-triazol-4-yl)pyrene (ttapyr) was designed and synthesized by "click" chemistry. This ligand was used to construct a linear dimetallic biscyclometalated Ru(II) complex [(tpy)Ru(ttapyr)Ru(tpy)](2+) and a monometallic complex [(tpy)Ru(ttapyr)](+), where tpy is 2,2':6',2″-terpyridine. The electronic properties of these complexes were studied and compared by electrochemical and spectroscopic methods with the aid of DFT calculations. One-electron oxidation of [(tpy)Ru(ttapyr)Ru(tpy)](2+) with cerium ammonium nitrate produced a mixed-valent complex [(tpy)Ru(ttapyr)Ru(tpy)](3+). The intramolecular electronic coupling between individual metal centers was quantified by the intervalence charge transfer transition analysis. Mixed-valent complex [(tpy)Ru(ttapyr)Ru(tpy)](3+) exhibits a metal-centered rhombic EPR signal at 77 K with an average g factor of 2.203.

  20. Synthesis, structure and characterisation of two 2,4-diamino-6-R-1,3,5-triazine derivatives ( R=3-cyanophenyl and 4-cyanophenyl)

    NASA Astrophysics Data System (ADS)

    Janczak, Jan; Kubiak, Ryszard

    2005-09-01

    Two triazine derivatives, 2,4-diamino-6-(3'-cyanophenyl)-1,3,5-triazine ( 1) and 2,4-diamino-6-(4'-cyanophenyl)-1,3,5-triazine ( 2), in the crystalline form by addition of cyanoguanidine to the 1,3- and 1,4-dicyanobenzene have been obtained. In both cases the addition of cyanoguanidine to the C tbnd6 N group of dicyanobenzene isomers and formation the triazine ring needs migration of both hydrogens from one amine group of cyanoguanidine to its cyano group. In the final step of the 1,3,5-triazine ring closing reaction, the C tbnd6 N group of dicyanobenzene contributes in the migration of hydrogen from one amine group to the cyano group of cyanoguanidine. The addition of cyanoguanidine molecule, in both cases (1,3-dicyanobenzene and 1,4-dicyanobenzene), takes place only when one of two C tbnd6 N groups of dicyanobenzene is incorporated into triazine ring. Both triazine derivatives crystallise in the monoclinic system in the space group of P2 1/ c ( 1) and C2/ c ( 2). In the crystal the molecules are not planar, but due to small rotations about the C-C bond the cyanophenyl and the 1,3,5-triazine rings are inclined by 3.4(1) and 17.3(1)° in 1 and 2, respectively. Meanwhile, the geometries of isolated molecules 1 and 2, both are planar, when optimised theoretically. Thus in the crystal the rotation of one ring in relation to other results from the intermolecular interactions like hydrogen bonds, π-π interactions between the aromatic rings and the crystal packing forces. The rotation barrier for the rings rotation around the inter-rings C-C bond is ˜28.4 and ˜27.7 kJ/mol for ( 1) and ( 2), respectively.

  1. 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...

  2. Organocatalytic asymmetric Michael addition of unprotected 3-substituted oxindoles to 1,4-naphthoquinone

    PubMed Central

    Yu, Jin-Sheng; Zhou, Feng; Liu, Yun-Lin

    2012-01-01

    Summary We reported the first example of organocatalytic Michael addition of unprotected 3-prochiral oxindoles 1 to 1,4-naphthoquinone. Quinidine derivative (DHQD)2PYR was found to be able to catalyze this reaction in up to 83% ee, with moderate to excellent yields. This method could be used for the synthesis of enantioenriched 3,3-diaryloxindoles, and the catalytic synthesis of which was unprecedented. PMID:23019472

  3. 4-Hy-droxy-1-methyl-3-phenyl-quinolin-2(1H)-one.

    PubMed

    Kafka, Stanislav; Pevec, Andrej; Proisl, Karel; Kimmel, Roman; Košmrlj, Janez

    2013-02-01

    In the title compound, C(16)H(13)NO(2), the quinoline system is approximately planar with a maximum deviation from the least-squares plane of 0.059 (1) Å for the N atom. The phenyl ring is rotated by 62.16 (4)° with respect to the plane of the quinoline system. In the crystal, O-H⋯O hydrogen bonds link mol-ecules into infinite chains running along the b-axis direction.

  4. Crystal structure of 4,4',4''-(1,3,5-triazine-2,4,6-tri-yl)tripyridinium trichloride 2.5-hydrate.

    PubMed

    Ling, Bo-Kai; Feng, Xiao-Long; Li, Yang; Luan, Tian-Gang

    2015-11-01

    The asymmetric unit of the title compound, C18H15N6 (3+)·3Cl(-)·2.5H2O, contains two independent (1,3,5-triazine-2,4,6-tri-yl)tripyridinium cations. Both cations are approximately planar, the r.m.s. deviations of fitted non-H atoms being 0.045 and 0.051 Å. In the crystal, extensive O-H⋯Cl, O-H⋯O, N-H⋯Cl and N-H⋯O hydrogen bonds and weak C-H⋯Cl and C-H⋯O inter-actions link the organic cations, Cl(-) anions and water mol-ecules into a three-dimensional supra-molecular architecture. π-π stacking between the pyridine rings of adjacent cations is also observed, the centroid-to-centroid distance being 3.7578 (8) Å.

  5. 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

  6. Solution and solid-supported synthesis of 3,4,5-trisubstituted 1,2,4-triazole-based peptidomimetics.

    PubMed

    Boeglin, Damien; Cantel, Sonia; Heitz, Annie; Martinez, Jean; Fehrentz, Jean-Alain

    2003-11-13

    [reaction: see text] 3,4,5-Trisubstituted 1,2,4-triazoles were synthesized in solution from various thioamides and hydrazides in smooth experimental conditions leading to peptidomimetic scaffolds. This strategy was found to be compatible with the usual peptide synthesis protecting groups. This methodology was then applied on solid support by anchoring alpha-amino acids through their amino function to an activated carbonate resin.

  7. New Organocatalytic Asymmetric Synthesis of Highly Substituted Chiral 2-Oxospiro-[indole-3,4'- (1',4'-dihydropyridine)] Derivatives.

    PubMed

    Auria-Luna, Fernando; Marqués-López, Eugenia; Mohammadi, Somayeh; Heiran, Roghayeh; Herrera, Raquel P

    2015-08-31

    Herein, we report our preliminary results concerning the first promising asymmetric synthesis of highly functionalized 2-oxospiro-[indole-3,4'-(1',4'-dihydropyridine)] via the reaction of an enamine with isatylidene malononitrile derivatives in the presence of a chiral base organocatalyst. The moderate, but promising, enantioselectivity observed (30%-58% ee (enantiomeric excess)) opens the door to a new area of research for the asymmetric construction of these appealing spirooxindole skeletons, whose enantioselective syntheses are still very limited.

  8. 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).

  9. Structures of Three Pyrazaboles: 1,3,5,7-Tetramethylpyrazabole; 4,4-Bis(pyrazol-1’-yl)pyrazabole; 4,4,8,8-Tetrakis(pyrazol-1’yl)pyrazabole.

    DTIC Science & Technology

    1984-11-01

    RL UNCLRSSIFIED NOV 84 UK/DC/TR-4 N88014-83-K-06ii F/G 7/ 3 NL I fl.m I .0i7 I I ~o II 1- 1111- 5 2- 111112.2 11111L -* ll l 40 ___ MICROCOPY RESOLUTION...Boron" • I. . - . . . ,--." " PACE 2 . b 21.765(2), c = 11.672(1) 1, = 09.51(1)’, V = 2118.9( 5 ) ? at 296 K, Z 4, D = 1.329 g cr- 3 IoKa, graphite...Positional parameters given in Table 5 and some bond lengths and angles in Tables 2 and 3 ; the molecular structure is illustrated in Figure 3

  10. 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.

  11. 2-Methyl-sulfanyl-5,6-dihydro-2H-1,3-dithiolo[4,5-b][1,4]dioxin-2-ium tetra-fluoro-borate.

    PubMed

    Zhou, Guoquan; Chen, Xinzhi

    2012-04-01

    The title compound, C(6)H(7)O(2)S(3) (+)·BF(4) (-), consists of a planar 2-thioxo-1,3-dithiol-4,5-yl unit [maximum deviation from the ring plane = 0.020 (3) Å], with an ethyl-enedi-oxy group fused at the 4,5-positions; the ethyl-enedi-oxy C atoms are disordered over two positions with site-occupancy factors of 0.5. The 1,4-dioxine ring has a twist-chair conformation. Weak cation-anion S⋯F inter-actions [3.022 (4)-3.095 (4) Å] and an S⋯O [3.247 (4) Å] inter-action are present.

  12. 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

  13. Spectroscopic Studies of Fluorescence Effects in Bioactive 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 Molecules Induced by pH Changes in Aqueous Solutions.

    PubMed

    Matwijczuk, Arkadiusz; Kluczyk, Dariusz; Górecki, Andrzej; Niewiadomy, Andrzej; Gagoś, Mariusz

    2017-03-01

    This paper presents the results of stationary fluorescence spectroscopy and time-resolved spectroscopy analyses of two 1,3,4-thiadiazole analogues, i.e. 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 an aqueous medium containing different concentrations of hydrogen ions. An interesting dual florescence effect was observed when both compounds were dissolved in aqueous solutions at pH below 7 for C1 and 7.5 for C7. In turn, for C1 and C7 dissolved in water at pH higher than the physiological value (mentioned above), single fluorescence was only noted. Based on previous results of investigations of the selected 1,3,4-thiadiazole compounds, it was noted that the presented effects were associated with both conformational changes in the analysed molecules and charge transfer (CT) effects, which were influenced by the aggregation factor. However, in the case of C1 and C7, the dual fluorescence effects were visible in a higher energetic region (different than that observed in the 1,3,4-thiadiazoles studied previously). Measurements of the fluorescence lifetimes in a medium characterised by different concentrations of hydrogen ions revealed clear lengthening of the excited-state lifetime in a pH range at which dual fluorescence effects can be observed. An important finding of the investigations presented in this article is the fact that the spectroscopic effects observed not only are interesting from the cognitive point of view but also can help in development of an appropriate theoretical model of molecular interactions responsible for the dual fluorescence effects in the analysed 1,3,4-thiadiazoles. Furthermore, the study will clarify a broad range of biological and pharmaceutical applications of these compounds, which are more frequently used in clinical therapies. Graphical Abstract Upper left corner - C7 molecule at high pH, right upper corner - fluorescence emission spectrum for C7 dissolved in H2

  14. (E)-1-([1,1′-Biphen­yl]-4-yl)-2-(1,3,3-tri­methylindolin-2-yl­idene)ethanone

    PubMed Central

    Vázquez-Vuelvas, Oscar F.; Pineda-Contreras, Armando; Morales-Morales, David; Hernández-Ortega, Simón; Tlenkopatchev, Mikhail

    2011-01-01

    The title compound, C25H23NO, consists of a biphenyl-4-carbonyl unit attached to an exocyclic double bond group at position 2 of an indole unit, which presents methyl groups as substituents at positions 1 and 3. The mol­ecular conformation is s-cis with an E configuration, supported by weak intra­molecular C—H⋯O contacts involving the methyl groups and the carbonyl function. The rings of the biphenyl group are twisted by 37.13 (5)°. In the crystal, C—H⋯O and C—H⋯π inter­actions link the molecules. PMID:22199738

  15. KNS4/UPEX1: A Type II Arabinogalactan β-(1,3)-Galactosyltransferase Required for Pollen Exine Development1[OPEN

    PubMed Central

    Suzuki, Toshiya; Narciso, Joan Oñate; Zeng, Wei; van de Meene, Allison; Yasutomi, Masayuki; Takemura, Shunsuke

    2017-01-01

    Pollen exine is essential for protection from the environment of the male gametes of seed-producing plants, but its assembly and composition remain poorly understood. We previously characterized Arabidopsis (Arabidopsis thaliana) mutants with abnormal pollen exine structure and morphology that we named kaonashi (kns). Here we describe the identification of the causal gene of kns4 that was found to be a member of the CAZy glycosyltransferase 31 gene family, identical to UNEVEN PATTERN OF EXINE1, and the biochemical characterization of the encoded protein. The characteristic exine phenotype in the kns4 mutant is related to an abnormality of the primexine matrix laid on the surface of developing microspores. Using light microscopy with a combination of type II arabinogalactan (AG) antibodies and staining with the arabinogalactan-protein (AGP)-specific β-Glc Yariv reagent, we show that the levels of AGPs in the kns4 microspore primexine are considerably diminished, and their location differs from that of wild type, as does the distribution of pectin labeling. Furthermore, kns4 mutants exhibit reduced fertility as indicated by shorter fruit lengths and lower seed set compared to the wild type, confirming that KNS4 is critical for pollen viability and development. KNS4 was heterologously expressed in Nicotiana benthamiana, and was shown to possess β-(1,3)-galactosyltransferase activity responsible for the synthesis of AG glycans that are present on both AGPs and/or the pectic polysaccharide rhamnogalacturonan I. These data demonstrate that defects in AGP/pectic glycans, caused by disruption of KNS4 function, impact pollen development and viability in Arabidopsis. PMID:27837085

  16. Ubiquitin Ligase NEDD4 Regulates PPARγ Stability and Adipocyte Differentiation in 3T3-L1 Cells

    PubMed Central

    Li, Jing Jing; Wang, Ruishan; Lama, Rati; Wang, Xinjiang; Floyd, Z. Elizabeth; Park, Edwards A.; Liao, Francesca-Fang

    2016-01-01

    Peroxisome proliferator–activated receptor-γ (PPARγ) is a ligand-activated nuclear receptor which controls lipid and glucose metabolism. It is also the master regulator of adipogenesis. In adipocytes, ligand-dependent PPARγ activation is associated with proteasomal degradation; therefore, regulation of PPARγ degradation may modulate its transcriptional activity. Here, we show that neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4), an E3 ubiquitin ligase, interacts with the hinge and ligand binding domains of PPARγ and is a bona fide E3 ligase for PPARγ. NEDD4 increases PPARγ stability through the inhibition of its proteasomal degradation. Knockdown of NEDD4 in 3T3-L1 adipocytes reduces PPARγ protein levels and suppresses adipocyte conversion. PPARγ correlates positively with NEDD4 in obese adipose tissue. Together, these findings support NEDD4 as a novel regulator of adipogenesis by modulating the stability of PPARγ. PMID:27917940

  17. Structural and theoretical study on the 1:2 addition complex of 1,2,4,5-bis{8‧,11‧-dithia[4.3.3]propella(3‧,4‧)}benzene with I2

    NASA Astrophysics Data System (ADS)

    Szlachcic, Paweł; Seidler, Tomasz; Stadnicka, Katarzyna

    2013-02-01

    The crystal structure of the title compound, C22H26S4·2I2, contains two centrosymmetric molecules of 1,2,4,5-bis{8',11'-dithia[4.3.3]propella(3',4')}benzene, and four I2 molecules in the unit cell of space group P21/c. The cyclohexene rings adopt boat conformation, whereas tetrahydrothiophene rings have envelope conformation. The iodine molecules are linked to one type of the sulphur atoms of the propellane molecule by a charge-transfer bond, with S⋯I distance of 2.7844(12) and I-I = 2.8153(5) Å. The second type of symmetrically independent sulphur atoms are engaged in a weak interaction of C-H⋯S type with the H⋯S distance of 3.09(1) Å. The geometry optimisation of the crystal structure at the B3LYP level with MIDI! basis set gave good agreement with the experimental data (S⋯I distance of 2.754 and I-I = 2.923 Å). NBO analysis for the complex showed that the S⋯I interaction is due to charge transfer from the lone pair on the sulphur to the vacant σ* orbital of the I2 acceptor.

  18. 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

  19. The contribution of human OCT1, OCT3, and CYP3A4 to nitidine chloride-induced hepatocellular toxicity.

    PubMed

    Li, Liping; Tu, Meijuan; Yang, Xi; Sun, Siyuan; Wu, Xiaodan; Zhou, Hui; Zeng, Su; Jiang, Huidi

    2014-07-01

    Nitidine chloride (NC), a quaternary ammonium alkaloid, has numerous pharmacological effects, such as anticancer activity. However, it was found that NC also has hepatocellular toxicity. Because organic cation transporters 1 and 3 (OCT1 and OCT3) might mediate the influx of NC into hepatocytes, multidrug and toxin extrusion 1 (MATE1) probably mediates the efflux of NC from hepatocytes, while cytochrome P450 (P450) enzymes might contribute to NC metabolism, the present study was to evaluate the contribution of OCT1, OCT3, MATE1, and P450 enzymes to NC-induced hepatocellular toxicity. Our results showed that the uptake of NC in Madin-Darby canine kidney (MDCK) cells expressing human (h) OCT1 and OCT3 (MDCK-hOCT1 and MDCK-hOCT3) was significantly higher than that in mock cells; the hOCT1- and hOCT3-mediated uptake followed typical Michaelis-Menten kinetics. Meanwhile, NC was also a substrate of hMATE1, although its transport capacity was much lower than that of OCT1 NC-induced cytotoxicity in MDCK-hOCT1 or MDCK-hOCT3 cells was obviously higher than that in mock cells. Quinidine and (+)-tetrahydropalmatine [(+)-THP], OCT1 and OCT3 inhibitors, significantly reduced the uptake of NC in MDCK-hOCT1 cells, MDCK-hOCT3 cells, and rat primary hepatocytes, but only (+)-THP markedly attenuated the NC-induced toxicity. In addition, P450 enzymes, such as CYP3A4, mediated the metabolism of NC, and NC-induced toxicity in MDCK-hOCT1/hCYP3A4 cells was lower than that in MDCK-hOCT1 cells. Our results indicated that NC is a substrate of hOCT1, hOCT3, and CYP3A4; that OCT1 and OCT3 mediate the uptake of NC in hepatocytes and subsequently cause hepatotoxicity; and that NC-induced toxicity could be attenuated by CYP3A4-mediated metabolism.

  20. 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.

  1. Synthesis and structure of a new copper(II) complex with 3,4'-bi-1,2,4-triazolate.

    PubMed

    Idouli, Y; Guédira, F; Rghioui, L; El Ammari, L; El Hajjaji, S; Zaydoun, S

    2011-01-01

    The salt diaquo-diammine-bis(3,4'-bi-1,2,4-triazolate) copper(II) of the formula [Cu(bTA-)2(NH3)2(H2O)2] has been synthesized and structurally characterized by X-ray single crystal diffraction analysis. This complex adopts a monomeric structure. This monomer crystallizes in the triclinic system, space group P1 with a=5.9657 Å; b=6.8975 Å; c=9.9892 Å; α=106.181°; β=97.868°; γ=90.800° and Z=1. The Cu atom is coordinated by two nitrogen atoms of two monodentate bitriazolate ligands, two nitrogen atoms of NH3 and two water molecules in a distorted octahedral geometry. The complex has been also characterized by elemental analysis and studied by electronic and vibrational spectroscopy. The obtained results are in good agreement with the structure determined by X-ray diffraction analysis.

  2. 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.

  3. 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.

  4. 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.

  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. Synergistic interactions between PDE4B and GSK-3: DISC1 mutant mice.

    PubMed

    Lipina, Tatiana V; Wang, Min; Liu, Fang; Roder, John C

    2012-03-01

    Disrupted-In-Schizophrenia-1 (DISC1) is a strong genetic risk factor associated with psychiatric disorders. Two distinct mutations in the second exon of the DISC1 gene (Q31L and L100P) lead to either depression- or schizophrenia-like behavior in mice. Both phosphodiesterase-4B (PDE4B) and glycogen synthase kinase-3 (GSK-3) have common binding sites on N-terminal region of DISC1 and are implicated into etiology of schizophrenia and depression. It is not known if PDE4B and GSK-3 could converge signals in the cell via DISC1 at the same time. The purpose of the present study was to assess whether rolipram (PDE4 inhibitor) might synergize with TDZD-8 (GSK-3 blocker) to produce antipsychotic effects at low doses on the DISC1-L100P genetic model. Indeed, combined treatment of DISC1-L100P mice with rolipram (0.1 mg/kg) and TDZD-8 (2.5 mg/kg) in sub-threshold doses corrected their Pre-Pulse Inhibition (PPI) deficit and hyperactivity, without any side effects at these doses. We have suggested that rolipram-induced increase of cAMP level might influence GSK-3 function and, hence the efficacy of TDZD-8. Our second goal was to estimate how DISC1-Q31L with reduced PDE4B activity, and therefore mimicking rolipram-induced conditions, could alter pharmacological response to TDZD-8, GSK-3 activity and its interaction with DISC1. DISC1-Q31L mutants showed increased sensitivity to GSK-3 inhibitor compare to DISC1-L100P mice. TDZD-8 (2.5 mg/kg) was able to correct PPI deficit, reduce immobility in the forced swim test (FST) and increased social motivation/novelty. In parallel, biochemical analysis revealed significantly reduced binding of GSK-3 to the mutated DISC1-Q31L and increased enzymatic activity of GSK-3. Taken together, genetic variations in DISC1 influence formation of biochemical complex with PDE4 and GSK-3 and strength the possibility of synergistic interactions between these proteins.

  7. Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters EAAT1, EAAT2, EAAT3, and EAAT4.

    PubMed

    Abousaab, Abeer; Warsi, Jamshed; Elvira, Bernat; Lang, Florian

    2016-06-01

    Excitatory amino acid transporters EAAT1 (SLC1A3), EAAT2 (SLC1A2), EAAT3 (SLC1A1), and EAAT4 (SLC1A6) serve to clear L-glutamate from the synaptic cleft and are thus important for the limitation of neuronal excitation. EAAT3 has previously been shown to form complexes with caveolin-1, a major component of caveolae, which participate in the regulation of transport proteins. The present study explored the impact of caveolin-1 on electrogenic transport by excitatory amino acid transporter isoforms EAAT1-4. To this end cRNA encoding EAAT1, EAAT2, EAAT3, or EAAT4 was injected into Xenopus oocytes without or with additional injection of cRNA encoding caveolin-1. The L-glutamate (2 mM)-induced inward current (I Glu) was taken as a measure of glutamate transport. As a result, I Glu was observed in EAAT1-, EAAT2-, EAAT3-, or EAAT4-expressing oocytes but not in water-injected oocytes, and was significantly decreased by coexpression of caveolin-1. Caveolin-1 decreased significantly the maximal transport rate. Treatment of EAATs-expressing oocytes with brefeldin A (5 µM) was followed by a decrease in conductance, which was similar in oocytes expressing EAAT together with caveolin-1 as in oocytes expressing EAAT1-4 alone. Thus, caveolin-1 apparently does not accelerate transporter protein retrieval from the cell membrane. In conclusion, caveolin-1 is a powerful negative regulator of the excitatory glutamate transporters EAAT1, EAAT2, EAAT3, and EAAT4.

  8. 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.

  9. 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.

  10. 1,4-Addition of TMSCCl3 to Nitroalkenes: Efficient Reaction Conditions and Mechanistic Understanding

    PubMed Central

    Wu, Na; Wahl, Benoit; Woodward, Simon; Lewis, William

    2014-01-01

    Improved synthetic conditions allow preparation of TMSCCl3 in good yield (70 %) and excellent purity. Compounds of the type NBu4X [X=Ph3SiF2 (TBAT), F (tetrabutylammonium fluoride, TBAF), OAc, Cl and Br] act as catalytic promoters for 1,4-additions to a range of cyclic and acyclic nitroalkenes, in THF at 0–25 °C, typically in moderate to excellent yields (37–95 %). TBAT is the most effective promoter and bromide the least effective. Multinuclear NMR studies (1H, 19F, 13C and 29Si) under anaerobic conditions indicate that addition of TMSCCl3 to TBAT (both 0.13 M) at −20 °C, in the absence of nitroalkene, leads immediately to mixtures of Me3SiF, Ph3SiF and NBu4CCl3. The latter is stable to at least 0 °C and does not add nitroalkene from −20 to 0 °C, even after extended periods. Nitroalkene, in the presence of TMSCCl3 (both 0.13 M at −20 °C), when treated with TBAT, leads to immediate formation of the 1,4-addition product, suggesting the reaction proceeds via a transient [Me3Si(alkene)CCl3] species, in which (alkene) indicates an Si⋅⋅⋅O coordinated nitroalkene. The anaerobic catalytic chain is propagated through the kinetic nitronate anion resulting from 1,4 CCl3− addition to the nitroalkene. This is demonstrated by the fact that isolated NBu4[CH2−NO2] is an efficient promoter. Use of H2C−CH(CH2)2CH−CHNO2 in air affords radical-derived bicyclic products arising from aerobic oxidation. PMID:24849249

  11. Heats of Formation for CF(sub n) (n = 1 - 4), CF(sup +, sub n) (n = 1 - 4), and CF(sup -, sub n) (n = 1 - 3)

    NASA Technical Reports Server (NTRS)

    Ricca, Alessandra; Arnold, James (Technical Monitor)

    1998-01-01

    Accurate heats of formation are computed for CF(sub n) (n = 1 - 4), CF(sup +, sub n) (n = 1 - 4), and CF(sup -, sub n) (n = 1 - 3). The geometries and vibrational frequencies are determined at the B3LYP level of theory. The energetics are determined at the CCSD(T) level of theory. Basis set limit values are obtained by extrapolation. In those cases where the CCSD(T) calculations become prohibitively large, the basis set extrapolation is performed at the MP2 level. The temperature dependence of the heat of formation, heat capacity, and entropy are computed for the temperature range 300 to 4000 K and fit to a polynomial.

  12. Synthesis and monoamine oxidase inhibitory activities of some 3-(4-fluorophenyl)-5-aryl-n-substituted-4,5-dihydro-(1H)-pyrazole-1-carbothioamide derivatives.

    PubMed

    Koç, G Ş; Tan, O U; Uçar, G; Yildirim, E; Erol, K; Palaska, E

    2014-11-01

    28 new 3-(4-fluorophenyl)-5-aryl-N-substituted-4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives were synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. The derivatives substituted by halogen on the fifth position of pyrazole ring, inhibited MAO-A enzyme with a high selectivity index. On the other hand, compounds substituted with 2-naphthyl inhibited MAO-B enzyme with a moderate selectivity index. Docking studies were done to highlight the interactions of the most active derivative with the active site of MAO-A. In addition, in vivo antidepressant and anxiolytic activities of the compounds having selective MAO-A inhibitory effects, were investigated by using Porsolt forced swimming and elevated plus-maze tests respectively. 3-(4-Fluorophenyl)-5-(4-chloro-phenyl)-N-allyl-4,5-dihydro-1H-pyrazole-1-carbothio-amide has antidepressant, 3-(4-fluorophenyl)-5-(4-chlorophenyl)-N-methyl-4,5-dihydro-1H-pyrazole-1-carbothioamide and 3-(4-fluoro-phenyl)-5-(4-bromophenyl)-N-ethyl-4,5-dihydro-1H-pyrazole-1-carbothioamide have anxiolytic activity.

  13. Proton Relaxation in 1, 3, 5-Triamino-2, 4, 6-Trinitrobenzene (TATB).

    DTIC Science & Technology

    1980-06-16

    AD-AO? 209 NAVAL RESEARCH LAB WASHINGTON DC F/G 7/4 PROTON RELAXATION IN 1. 3, 5-TRIAMINO-2, 4. 6-TRINITROBENZENE C-ETC(Ul~JUN A0 A N GARROWAY , H A...TATB) 1 April - 31 September 1979 S. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(a) S. CONTRACT OR GRANT NUMBER(@) A.N. Garroway and H.A. Resing DE-AP-03

  14. Distribution, structure and biosynthetic gene families of (1,3;1,4)-β-glucan in Sorghum bicolor.

    PubMed

    Ermawar, Riksfardini A; Collins, Helen M; Byrt, Caitlin S; Betts, Natalie S; Henderson, Marilyn; Shirley, Neil J; Schwerdt, Julian; Lahnstein, Jelle; Fincher, Geoffrey B; Burton, Rachel A

    2015-04-01

    In cereals, the presence of soluble polysaccharides including (1,3;1,4)-β-glucan has downstream implications for human health, animal feed and biofuel applications. Sorghum bicolor (L.) Moench is a versatile crop, but there are limited reports regarding the content of such soluble polysaccharides. Here, the amount of (1,3;1,4)-β-glucan present in sorghum tissues was measured using a Megazyme assay. Very low amounts were present in the grain, ranging from 0.16%-0.27% (w/w), while there was a greater quantity in vegetative tissues at 0.12-1.71% (w/w). The fine structure of (1,3;1,4)-β-glucan, as denoted by the ratio of cellotriosyl and cellotetraosyl residues, was assessed by high performance liquid chromatography (HPLC) and ranged from 2.6-3:1 in the grain, while ratios in vegetative tissues were lower at 2.1-2.6:1. The distribution of (1,3;1,4)-β-glucan was examined using a specific antibody and observed with fluorescence and transmission electron microscopy. Micrographs showed a variable distribution of (1,3;1,4)-β-glucan influenced by temporal and spatial factors. The sorghum orthologs of genes implicated in the synthesis of (1,3;1,4)-β-glucan in other cereals, such as the Cellulose synthase-like (Csl) F and H gene families were defined. Transcript profiling of these genes across sorghum tissues was carried out using real-time quantitative polymerase chain reaction, indicating that, as in other cereals, CslF6 transcripts dominated.

  15. Atomic origin of 3d(9)4 f(1) configuration in La(3+) solids.

    PubMed

    Yu, S-W; Carpenter, M H; Ponce, F; Friedrich, S; Lee, J-S

    2015-10-14

    We have studied the excited electronic structure of LaBr3(Ce) scintillator by soft x-ray spectroscopy such as x-ray absorption spectroscopy (XAS) and x-ray emission spectroscopy (XES). The La 3d XAS and XES spectra of LaBr3(Ce) are compared with those of other La(3+) solids (LaF3, La2O3, and La metal). From this comparison, it turns out that the La 3d XAS and XES spectra from all the La(3+) solids considered here appear at almost the same energy, even though the corresponding binding energies of the 3d core holes determined by XPS (x-ray photoelectron spectroscopy) are very different. As a result, we argue that the atomic nature of the 3d⁹4f¹ configuration created by 3d¹⁰4f⁰ → 3d⁹4f¹ x-ray absorption process in La(3+) solids is maintained via the localized 4 f (1) state, which screens the 3d core holes differently from one La(3+) solid to another.

  16. 4,4-Dimethyl-2-[3-nitro-2-phenyl-1-(phenyl­sulfan­yl)prop­yl]-4,5-dihydro-1,3-oxazole

    PubMed Central

    Caracelli, Ignez; Zukerman-Schpector, Julio; Villar, José A. F. P.; Oliveira, Alfredo R. M.; Tiekink, Edward R. T.

    2012-01-01

    In the title compound, C20H22N2O3S, the oxazoline ring is planar (r.m.s. deviation = 0.045 Å) and forms dihedral angles of 47.24 (8) and 10.11 (8)° with the S- and C-bound phenyl rings, respectively. The nitro group lies to the same side of the mol­ecule as the oxazoline ring but is orientated so as not to inter­act with the ring. Linear supra­molecular chains along [010] are formed via C—H⋯O and C—H⋯S contacts. Chains are consolidated into a three-dimensional architecture by C—H⋯π and van der Waals inter­actions. PMID:22606161

  17. 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

  18. 40 CFR 721.10187 - 4-Morpholinepropanamine, N-(1,3-dimethylbutylidene)-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10187 4-Morpholinepropanamine, N-(1,3-dimethylbutylidene)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  19. 40 CFR 721.10187 - 4-Morpholinepropanamine, N-(1,3-dimethylbutylidene)-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10187 4-Morpholinepropanamine, N-(1,3-dimethylbutylidene)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  20. 26 CFR 1.702-3T - 4-Year spread (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) INCOME TAXES (CONTINUED) Partners and Partnerships § 1.702-3T 4-Year spread (temporary). (a) Applicability. This section applies to a partner in a partnership if— (1) The partnership is required by section... partnership would, but for the provisions of this section, be included in the taxable year of the partner...

  1. 26 CFR 1.702-3T - 4-Year spread (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) INCOME TAXES Partners and Partnerships § 1.702-3T 4-Year spread (temporary). (a) Applicability. This section applies to a partner in a partnership if— (1) The partnership is required by section 806... partnership would, but for the provisions of this section, be included in the taxable year of the partner...

  2. Convenient large-scale synthesis of D-glucaro-1,4:6,3-dilactone.

    PubMed

    Gehret, Troy C; Frobese, A Stephen; Zerbe, James S; Chenault, H Keith

    2009-11-06

    Calcium D-glucarate was converted into D-glucaro-1,4:6,3-dilactone on 32-g, 1-kg, and 22-kg scale, using azeotropic distillation with methyl isobutyl ketone to drive the dehydration. The crystalline product was > or = 99.5% pure by GC and NMR, and overall yield was as high as 72%.

  3. [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

  4. 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.

  5. 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

  6. In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)

    DOE PAGES

    Choi, Taylor A.; Furimsky, Anna M.; Swezey, Robert; ...

    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

  7. 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.

  8. In vitro metabolism and stability of the actinide chelating agent 3,4,3-LI(1,2-HOPO).

    PubMed

    Choi, Taylor A; Furimsky, Anna M; Swezey, Robert; Bunin, Deborah I; Byrge, Patricia; Iyer, Lalitha V; Chang, Polly Y; Abergel, Rebecca J

    2015-05-01

    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 min, 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 coadministered 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 bidirectional 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.

  9. Synthesis, Antimicrobial and Antiinflammatory Activity of 2,5-Disubstituted-1,3,4-oxadiazoles

    PubMed Central

    Nagalakshmi, G.

    2008-01-01

    In the present study, 2,5-disubstituted-1,3,4-oxadiazoles (3a-o) have been synthesized by the condensation of 4-methoxybenzohydrazide (1) with different aromatic acids (2a-o) in presence of phosphoryl chloride. The structural assignment of this compound (3a-o) has been made on the basis of elemental analysis, UV, IR, 1H NMR and mass spectral data. The synthesized compounds were screened for their in vitro growth inhibiting activity against different strains of bacteria and fungi viz., Staphylococcus aureus, Bacillus subtilis, Bacillus megaterium, Escherichia coli, Pseudomonas aeruginosa, Shigella dysenteriae, Candida albicans, Aspergillus niger and Aspergillus flavus were compared with the standard antibiotics such as chloramphenicol (50 μg/ml) and griseofulvin (50 μg/ml) using well agar diffusion technique. Compounds 3e, 3g, 3h and 3m exhibits highest antibacterial activity and compounds 3d, 3g and 3h showed better antifungal activity. The synthesized compounds (3a-o) were screened for their in vitro antiinflammatory activity against carrageenan-induced rat paw oedema. Compounds 3f and 3i were found to be most active compound of this series, which shows 46.42% and 50% inflammation inhibitory activity, whereas standard drug phenylbutazone exhibit 53.57% antiinflammatory activity at a dose of 50 mg/kg po. PMID:20390080

  10. 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...

  11. 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

  12. Biosynthesis of murein lipoprotein in Escherichia coli: effects of 3,4-dihydroxybutyl-1-phosphonate.

    PubMed Central

    Chattopadhyay, P K; Engel, R; Tropp, B E; Wu, H C

    1979-01-01

    The effects of 3,4-dihydroxybutyl-1-phosphonate, a four-carbon analog of sn-glycerol 3-phosphate, on the biosynthesis of the glyceryl moiety in murein lipoprotein of Escherichia coli were studied. The compound at a concentration of 55 microM strong inhibits in the incorporation of [2-3H]glycerol radioactivity into lipoprotein by virtue of its inhibition of the synthesis of phosphatidylglycerol. On the other hand, the incorporation of prelabeled [2-3H]glycerol radioactivity into lipoprotein was only partially inhbited by 3,4-dihydroxybutyl-1-phosphonate even at a much higher concentration (1 mM). These data were consistent with the postulated pathway for the biosynthesis of the lipid moiety in lipoportein: cysteine-lipoprotein + phosphatidylglycerol leads to glycerylcystein-lipoprotein + phosphatidic acid. PMID:378946

  13. 3-(4-Chloro-phenyl-diazen-yl)-1-methyl-1,4,5,6-tetra-hydro-pyridine.

    PubMed

    Meneghetti, Fiorella; Bombieri, Gabriella; Tonelli, Michele

    2008-06-19

    The title compound, C(12)H(14)ClN(3), represents the planar azoenamine tautomer. The benzene ring forms a dihedral angle of 2.5 (1)° with the azoenamine group. Electron delocalization is indicated by the values of the bond lengths in the chain. The tetra-hydro-pyridine ring adopts a half-chair conformation and the dihedral angle between the least-squares plane defined by the five coplanar C atoms and the azoenamine unit is 2.0 (1)°, while the envelope-flap C atom lies out of this plane by 0.579 (2) Å. The mol-ecular packing is governed by van der Waals inter-actions through the stacking of adjacent mol-ecules, resulting in a two-dimensional sheet structure.

  14. In vitro BALB/3T3 cell transformation assay of nonoxynol-9 and 1,4-dioxane.

    PubMed

    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 micrograms/ml, did not induce transformation, whereas dioxane was very active in the induction of type III foci in the cultured BALB/3T3 cells.

  15. [Synthesis and luminiescence of Eu(III) complex based on 4,4,4-trifluoro-1-(4'-m-terphenyl)-1, 3-butanedione and 1,10-phenanthroline].

    PubMed

    Liu, Sheng-Gui; Lin, Cheng-You; Wang, Hui-Hui; He, Pei; Gong, Meng-Lian

    2010-03-01

    A new europium (III) complex, EuL3 phen, [HL = 4,4,4-trifluoro-1-(4'-m-terphenyl)-1,3-butanedione, phen = 1, 10-phenanthroline] was synthesized. Its structure was characterized by elemental analysis, IR and FAB-MS. The complex exhibits strongly red emission due to the 5D0-7F(J) (J = 0-4) transitions of Eu3+ ions under irradiation of UV or 395 nm emission light of InGaN chip. The strongest emission peak is located at 613 nm. The luminescence quantum yield is 13%. The lifetime of the complex is 470 micros. The decay curve can be fit with a single exponential. The thermogravimetric analyses curve for the complex shows that the complex is stable up to 220 degrees C, which meets the requirement of fabrication of LED device. A red luminescent LED was successfully fabricated by coating complex EuL3 phen onto 395 nm emitting InGaN chip. The mass ratio of complex to the silicone is related to the chromaticity coordinates and efficiency of fabricated LED. When the mass ratio of complex to the silicone is 1 : 25, the chromaticity coordinates of the fabricated LED with the europium complex are x = 0.64 and y = 0.35 and the efficiency achieves 0.89 lm x W(-1). The results indicate that the complex may act as a potential red component in the fabrication of white LEDs.

  16. 1-(3,5-Dinitro-1H-pyrazol-4-yl)-3-nitro-1H-1,2,4-triazol-5-amine (HCPT) and its energetic salts: highly thermally stable energetic materials with high-performance.

    PubMed

    Li, Chuan; Zhang, Man; Chen, Qishan; Li, Yingying; Gao, Huiqi; Fu, Wei; Zhou, Zhiming

    2016-11-28

    A novel energetic heat-resistant explosive, 1-(3,5-dinitro-1H-pyrazol-4-yl)-3-nitro-1H-1,2,4-triazol-5-amine (HCPT), has been synthesized along with its salts. An intensive characterization of the compounds is given, including (1)H and (13)C NMR spectroscopy, IR spectroscopy, and elemental analysis. The crystal structures of neutral HCPT (3), its triaminoguanidinium salt (10), 3,4,5-triamino-1,2,4-triazolium salt (12), and copper(ii) complex (16) were determined by single-crystal X-ray diffraction. The physicochemical properties of the compounds, such as density, thermal stability, and sensitivity towards impact and friction were evaluated; all energetic compounds exhibited excellent thermal stabilities with decomposition temperatures ranging from 215 °C to 340 °C, and high positive heats of formation between 622.8 kJ mol(-1) and 1211.7 kJ mol(-1). The detonation pressures and velocities for the energetic compounds were calculated using EXPLO5 (V6.01) based on experimental densities and calculated heats of formation, and the corresponding values were in the ranges of 26.5 GPa to 37.8 GPa and 8236 m s(-1) to 9167 m s(-1). Based on thermal stability values and energetic parameters, compounds 3 and 7 were superior to those of all of the commonly used heat-resistant explosives, which may find potential application as heat-resistant energetic materials.

  17. Organically templated uranium(IV) fluorooxalates with layer structures: (H4TREN)[U2F6(C2O4)3].4H2O (TREN = tris(2-aminoethyl)amine) and (H4APPIP)[U2F6(C2O4)3].4H2O (APPIP = 1,4-bis(3-amino-propyl)piperazine).

    PubMed

    Wang, Chih-Min; Wu, Yi-Ying; Chen, Pei-Lin; Lii, Kwang-Hwa

    2007-03-14

    Two organically-templated layered uranium(IV) fluorooxalates, (H(4)TREN)[U(2)F(6)(C(2)O(4))(3)].4H(2)O (1) (TREN = tris(2-aminoethyl)amine) and (H(4)APPIP)[U(2)F(6)(C(2)O(4))(3)].4H(2)O (2) (APPIP = 1,4-bis(3-aminopropyl)piperazine), have been synthesized by hydrothermal methods and structurally characterized by single-crystal X-ray diffraction, thermogravimetric analysis, and magnetic susceptibility. Both structures consist of anionic [U(2)F(6)(C(2)O(4))(3)](4-) layers separated by organic ammonium cations and lattice water molecules. The UF(3)O(6) polyhedra are connected by oxalate ligands in different ways within the layers. They are the first examples of organically-templated uranium fluorooxalates. Crystal data for compound 1 follow: monoclinic, P2(1)/c (No. 14), a = 19.1563(5) A, b = 8.9531(2) A, c = 16.6221(4) A, beta = 114.633(1) degrees, and Z = 4. Crystal data for compound are the same as those for 1 except a = 10.3309(8) A, b = 15.564(1) A, c = 17.537(1) A, and beta = 95.430(4) degrees.

  18. Trimethylation of Histone H3 Lysine 4 by Set1 in the Lytic Infection of Human Herpes Simplex Virus 1

    PubMed Central

    Huang, Jing; Kent, Jennifer R.; Placek, Brandon; Whelan, Kelly A.; Hollow, Charles M.; Zeng, Ping-Yao; Fraser, Nigel W.; Berger, Shelley L.

    2006-01-01

    Human herpes simplex virus 1 (HSV-1) is a double-stranded DNA virus that causes facial, ocular, and encephalitic disease in humans. Previous work showed that the genome of HSV-1 is associated with acetylated and methylated histones during lytic infection. However, the physiological role of histone modifications in lytic infection of HSV-1 is unclear. We examined the role of protein methylation in lytic infection of HSV-1 using a protein methylation inhibitor, 5′-deoxy-5′-methylthioadenosine (MTA). We found that MTA strongly reduces the transcription and replication of HSV-1. Moreover, MTA treatment decreases the level of trimethylation of lysine 4 in histone H3 (H3K4me3) on the HSV-1 genome. These results suggest that protein methylation, and in particular, histone methylation, is involved in the lytic infection of HSV-1. To delineate the underlying mechanism, we investigated the role of two H3K4 methyltransferases, Set1 and Set7/9, in the lytic infection of HSV-1. Using small interference RNA, we found that the reduction of Set1, but not Set7/9, reduces the transcription and replication of HSV-1 and specifically decreases H3K4me3 on the virus genome. These results indicate that H3K4me3 mediated by Set1 is required for optimal gene expression and replication of HSV-1 during lytic infection and suggest that this pathway could be a potential point of pharmacological intervention during HSV-1 infection. PMID:16731913

  19. Chiral pyridin-3-ones and pyridines: syntheses of enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones, 2,3-disubstituted 4-iodopyridines, and enantiopure 2,3-disubstituted 4-pyridinemethanols.

    PubMed

    Husain, Irfan; Saquib, Mohammad; Bajpai, Vikas; Kumar, Brijesh; Shaw, Arun K

    2011-11-04

    The development of an innovative method to access enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones starting from D-glucal via the aza-Achmatowicz transformation has been described. These highly functionalized pyridin-3-ones have been utilized for the synthesis of contiguously substituted pyridines through a rapid and efficient Et(3)N/Ac(2)O promoted cyclo-elimination, aromatization cascade, allowing the facile assembly of important pyridine-based building blocks like 2-substituted 3-acetoxy-4-iodopyridines and enantiopure 2-substituted 3-acetoxy-4-pyridinemethanols possessing benzylic stereogenic centers, whose synthesis otherwise would be tedious. The utilization of commercially available sugars as starting materials, mild reaction conditions, catalytic transfer hydrogen (CTH) of α-furfuryl azide derivatives, transfer of chiral aryl/alkyl methanols from enulosides to pyridin-3-ones and pyridines, high yields, and short reaction times are key features of this method. The utility of the method has been further exemplified by demonstrating the usage of the 2-substituted 3-acetoxy-4-iodopyridine for the construction of biologically significant molecules like 2,7-disubstituted furo[2,3-c]pyridines and 7,7'-disubstituted 2,2'-bifuro[2,3-c]pyridines.

  20. Investigation of 1-(4-morpholinophenyl)-3-(4-fluorophenyl)-propenone and 1-(4-morpholinophenyl)-3-(3-fluorophenyl)-propenone as new apoptosis inducers on Spodoptera frugiperda (Sf9) cells.

    PubMed

    Zhang, Xingang; Tao, Ke; Hou, Taiping

    2012-05-01

    The objective of this study was to examine the toxicity of 1-(4-morpholinophenyl)-3-(4-fluorophenyl)-propenone (A) and 1-(4-morpholinophenyl)-3-(3-fluorophenyl)-propenone (B) on Spodoptera frugiperda (Sf9) cells and the mechanism of the toxicity. By cell-based thiazolyl blue tetrazolium bromide (MTT) assay, we found that the IC(50) were 35.45 μM for A and 31.97 μM for B respectively. Formation of apoptotic bodies was observed at 24 h in the treated cells. There was a significant increase of DNA ladders in the treated Sf9 cells compared to controls. In the presence of 50 μM compound A and B for 24 h, ATP content of Sf9 cells reduced by approximately 50%. Compared to the controls, the significant over-expression of caspase-3 in treated cells was measured by caspase-3 activity kit, and the loss of mitochondrial membrane potential (ΔΨm) was detected in apoptosis cells. The results suggested that the two compounds could be identified as new potent cell apoptosis inducers.

  1. 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.

  2. 1-aryl-6,7-methylenedioxy-3H-quinazolin-4-ones as anticonvulsant agents.

    PubMed

    Zappalà, Maria; Grasso, Silvana; Micale, Nicola; Zuccalà, Giuseppe; Menniti, Frank S; Ferreri, Guido; De Sarro, Giovambattista; De Micheli, Carlo

    2003-12-15

    A set of novel 1-aryl-6,7-methylenedioxy-3H-quinazolin-4-(thi)ones (3a-f) has been designed and screened as anticonvulsant agents in DBA/2 mice. The new compounds are provided with anticonvulsant properties comparable to those of GYKI 52466. To clarify the mode of action, their affinity for the quinazolinone/2,3-benzodiazepine site of the AMPA receptor complex has been assayed.

  3. The assembly of two isomorphous coordination compounds based on 1,4-cyclohexanedicarboxylic acid and 2,4-diamino-6-phenyl-1,3,5-triazine

    NASA Astrophysics Data System (ADS)

    Li, Xue-Fei; Wang, Xiao; Lun, Hui-Jie; Jin, Lin-Yu; Li, Ya-Min; Yang, Jing-He

    2017-02-01

    The compounds [Co(e,a-cis-1,4-chdc)(phdat)]n (1) and [Cd(e,a-cis-1,4-chdc)(phdat)]n (2) have been synthesized under hydrothermal method by using 1,4-cyclohexanedicarboxylic acid (1,4-H2chdc), 2,4-diamino-6-phenyl-1,3,5-triazine (phdat) as well as CoCl2·6H2O, CdCl2·2.5H2O respectively and characterized by IR spectra, X-ray single-crystal diffraction, powder X-ray single-crystal diffraction (PXRD), elemental analyses and thermogravimetric analyses (TGA). The results show the compounds 1 and 2 are isomorphous and exhibit paddle-wheel dinuclear Co2(CO2)4/Cd2(CO2)4 units, which are further connected to 1D chain structures by μ41111 1,4-chdc2- ligands and extended into a 3D structures via different hydrogen bonding and π…π stacking interactions. Furthermore, compound 1 exhibits antiferromagnetic behavior and compound 2 displays luminescent behavior at solid state.

  4. The antinociceptive effect of 4-substituted derivatives of 5-(4-chlorophenyl)-2-(morpholin-4-ylmethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione in mice.

    PubMed

    Joanna, Listos; Talarek, Sylwia; Orzelska, Jolanta; Fidecka, Sylwia; Wujec, Monika; Plech, Tomasz

    2014-04-01

    The aim of the present experiments was to examine the antinociceptive activity of 4-substituted derivatives of 5-(4-chlorophenyl)-2-(morpholin-4-ylmethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione in mice. The compounds were synthesized using the so-called Mannich reaction and their structures were confirmed using IR and 1H-NMR spectra. The antinociceptive activity was investigated in two behavioral tests: the hot plate test and the writhing test. For preliminary estimation of other behavioral effects, the locomotor activity of mice, the motor coordination in the rota-rod test, and the myorelaxation in the chimney test were also studied. The changes in body temperature of animals were also recorded. We demonstrated that all examined compounds produced antinociceptive effect, both in the hot plate test and in the writhing test, without impact on the motor coordination and myorelaxation of animals. The pharmacological effect of all drugs has been developed within 60 min after administration of drugs; and in two cases (T-103 and T-104), it has been a short-lasting effect (up to 90 min). Two compounds (T-100 and T-102) also inhibited the locomotor activity of animals. T-104 induced the changes in body temperature of mice. Generally, we demonstrated that combination of two different heterocyclic systems (morpholine and 1,2,4-triazole) might be beneficial for reduction of nociception.

  5. Enzymatic Analysis of PTEN Ubiquitylation by WWP2 and NEDD4-1 E3 Ligases

    PubMed Central

    Chen, Zan; Thomas, Stefani N.; Bolduc, David M.; Jiang, Xuejun; Zhang, Xiangbin; Wolberger, Cynthia; Cole, Philip A.

    2016-01-01

    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

  6. Derivatives of 1,3-disubstituted 2,4(1H,3H)-quinazolinediones as possible peripheral vasodilators or antihypertensive agents.

    PubMed

    Havera, H J; Vidrio, H

    1979-12-01

    A series of 1,3-disubstituted 2,4(1H,3H)-quinazolinediones was prepared from the 3-substituted 2,4(1H,3H)-quinazolinediones by treatment with sodium hydride and the desired alkyl halide in xylene. These compounds showed varying degrees of vasodilation and antihypertensive activity without significant blockade of alpha-adrenergic receptors. 1-[3-(N,N-Dimethylamino)propyl]-3-[3-(4-phenyl1-piperazinyl)propyl]-2,4(1H,3H)-quinazolinedione, which was selected for further studies, was more potent than papaverine in inducing vasodilation and induced a prolonged decrease in systolic blood pressure of hypertensive rats upon oral administration.

  7. Enantioseparation, absolute configuration determination, and anticonvulsant activity of (+/-)-1-(4-aminophenyl)-7,8-methylenedioxy-1,2,3,5-tetrahydro-4H-2,3-benzodiazepin-4-one.

    PubMed

    Calabrò, Maria Luisa; Raneri, Daniela; Ficarra, Paola; Ferreri, Guido; De Sarro, Giovambattista; Bruno, Giuseppe; Zappalà, Maria; Micale, Nicola; Grasso, Silvana

    2007-01-01

    The resolution of 1-(4-aminophenyl)-7,8-methylenedioxy-1,2,3,5-tetrahydro-4H-benzodiazepin-4-one (+/-)-(R,S)-2 was accomplished by chiral HPLC. The absolute configuration of (+)-2, determined by X-ray crystallographic analysis, was R. The in vivo anticonvulsant activity of the enantiomers (+)-(R)-2 and (-)-(S)-2 is reported. It has been also demonstrated that compound (+/-)-(R,S)-2 in vivo undergoes oxidative metabolism to derivative 1.

  8. Synthesis and biological evaluation of 4-(1,2,3-triazol-1-yl)coumarin derivatives as potential antitumor agents.

    PubMed

    Zhang, Wenjuan; Li, Zhi; Zhou, Meng; Wu, Feng; Hou, Xueyan; Luo, Hao; Liu, Hao; Han, Xuan; Yan, Guoyi; Ding, Zhenyu; Li, Rui

    2014-02-01

    In this research, a series of 4-(1,2,3-triazol-1-yl)coumarin conjugates were synthesized and their anticancer activities were evaluated in vitro against three human cancer cell lines, including human breast carcinoma MCF-7 cell, colon carcinoma SW480 cell and lung carcinoma A549 cell. To increase the biological potency, structural optimization campaign was conducted focusing on the C-4 position of 1,2,3-triazole and the C-6, C-7 positions of coumarin. In addition, to further evaluate the role of 1,2,3-triazole and coumarin for antiproliferative activity, 9 compounds possessing 4-(piperazin-1-yl)coumarin framework and 3 derivatives baring quinoline core were also synthesized. By MTT assay in vitro, most of the compounds display attractive antitumor activities, especially 23. Further flow cytometry assays demonstrate that compound 23 exerts the antiproliferative role through arresting G2/M cell-cycle and inducing apoptosis.

  9. Design and synthesis of novel 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles as selective COX-2 inhibitors with potent anti-inflammatory activity.

    PubMed

    Bansal, Sumit; Bala, Manju; Suthar, Sharad Kumar; Choudhary, Shivani; Bhattacharya, Shoumyo; Bhardwaj, Varun; Singla, Sumit; Joseph, Alex

    2014-06-10

    A novel series of 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles were designed and synthesized for selective COX-2 inhibition with potent anti-inflammatory activity. Among the compounds tested, 9g (2-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazole) was found to be the most potent inhibitor of COX-2 with IC50 of 0.31 μM showing promising degree of anti-inflammatory activity in the carrageenan-induced rat paw edema model with ED50 of 74.3 mg/kg. The lead compound 9g further showed suppression of acetic acid-induced writhes comparable to that of aspirin and gastro-sparing profile superior to the aspirin. Molecular docking analysis displayed higher binding affinity of ligands towards COX-2 than COX-1.

  10. Synthesis, Characterization and Biological Activity Studies of 1,3,4-Oxadiazole Analogs

    PubMed Central

    Bhat, KI; Sufeera, K; Chaitanya, Sunil Kumar P

    2011-01-01

    The reaction of p-bromoanilino acetohydrazide(II) with aromatic aldehydes in alcohol yielded 2-[4-bromo aniline] N-substituted benzylidine hydrazides (IIIa-IIIj), which in presence of yellow mercuric oxide and iodine in DMF, yielded corresponding 4-bromo[(N-5-substituted 1,3,4 oxadiazole-2 –yl)methyl]aniline (IVa-IVj). Structures of the compounds synthesized were confirmed by IR, 1HNMR and MASS spectroscopic analysis. The newly synthesized compounds were screened for antibacterial, antifungal and anti-inflammatory activities. Some of the compounds showed remarkable antibacterial, antifungal and anti-inflammatory activities. PMID:22224038

  11. Crystal structure of 1-benzyl-4-formyl-1H-pyrrole-3-carb­oxamide

    PubMed Central

    Zhong, Qi-Di; Hu, Sheng-Quan; Yan, Hong

    2016-01-01

    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 intra­molecular N—H⋯O hydrogen bond forming an S(7) ring motif. In the crystal, mol­ecules 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 inter­actions forming layers parallel to the ac plane. PMID:26958371

  12. 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.

  13. Dihydropyridine Ca2+ channel antagonists and agonists block Kv4.2, Kv4.3 and Kv1.4 K+ channels expressed in HEK293 cells.

    PubMed

    Hatano, Noriyuki; Ohya, Susumu; Muraki, Katsuhiko; Giles, Wayne; Imaizumi, Yuji

    2003-06-01

    (1) We have determined the molecular basis of nicardipine-induced block of cardiac transient outward K(+) currents (I(to)). Inhibition of I(to) was studied using cloned voltage-dependent K(+) channels (Kv) channels, rat Kv4.3L, Kv4.2, and Kv1.4, expressed in human embryonic kidney cell line 293 (HEK293) cells. (2) Application of the dihydropyridine Ca(2+) channel antagonist, nicardipine, accelerated the inactivation rate and reduced the peak amplitude of Kv4.3L currents in a concentration-dependent manner (IC(50): 0.42 micro M). The dihydropyridine (DHP) Ca(2+) channel agonist, Bay K 8644, also blocked this K(+) current (IC(50): 1.74 micro M). (3) Nicardipine (1 micro M) slightly, but significantly, shifted the voltage dependence of activation and steady-state inactivation to more negative potentials, and also slowed markedly the recovery from inactivation of Kv4.3L currents. (4) Coexpression of K(+) channel-interacting protein 2 (KChIP2) significantly slowed the inactivation of Kv4.3L currents as expected. However, the features of DHP-induced block of K(+) current were not substantially altered. (5) Nicardipine exhibited similar block of Kv1.4 and Kv4.2 channels stably expressed in HEK293 cells; IC(50)'s were 0.80 and 0.62 micro M, respectively. (6) Thus, at submicromolar concentrations, DHP Ca(2+) antagonist and agonist inhibit Kv4.3L and have similar inhibiting effects on other components of cardiac I(to), Kv4.2 and Kv1.4.

  14. Degradation of 1,2,3,4-tetrachlorobenzene by Pseudomonas chlororaphis RW71

    SciTech Connect

    Potrawfke, T.; Timmis, K.N.; Wittich, R.M.

    1998-10-01

    Pseudomonas chlororaphis RW71 mineralized 1,2,3,4-tetrachlorobenzene, a highly recalcitrant pollutant hitherto not known to be degraded by pure cultures, as a sole source of carbon and energy, thereby releasing stoichiometric amounts of chloride. The transient excretion of tetrachlorocatechol in the early growth phase suggests an initial attack by a dioxygenase to form the corresponding dihydrodiol which rearomatizes to the catechol. The activity of chlorocatechol 1,2-dioxygenase in crude cell extracts was found to be extraordinarily high towards 3-chlorocatechol (ratio of 2.6 compared to catechol) and other chlorocatechols, including tetrachlorocatechol, which was transformed at a low but significant rate. Further identification of tetrachloromuconic acid, 2,3,5-trichlorodienelactone, 2,3,5-trichloromaleyl acetic acid, and 2,4-dichloro-3-oxoadipic acid as their methyl esters, together with high specific enzyme activities for chlorinated substrates, implicated a functioning chlorocatechol pathway to be induced during growth.

  15. Synthesis and biological evaluation of new imidazo[2,1-b][1,3,4]thiadiazole-benzimidazole derivatives.

    PubMed

    Ramprasad, Jurupula; Nayak, Nagabhushana; Dalimba, Udayakumar; Yogeeswari, Perumal; Sriram, Dharmarajan; Peethambar, S K; Achur, Rajeshwara; Kumar, H S Santosh

    2015-05-05

    In this report, we describe the synthesis and biological evaluation of a new series of 2-(imidazo[2,1-b][1,3,4]thiadiazol-5-yl)-1H-benzimidazole derivatives (5a-ac). The molecules were analyzed by (1)H NMR, (13)C NMR, mass spectral and elemental data. The structure of one of the pre-final compounds, 6-(4-methoxyphenyl)-2-(4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde (4d) and that of a target compound, 2-[2-methyl-6-(4-methyl phenyl) imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-1H-benzimidazole (5aa) were confirmed by single crystal XRD studies. All the target compounds were screened for in vitro anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv strain. Seven (5c, 5d, 5l, 5p, 5r, 5z and 5aa) out of twenty nine compounds showed potent anti-tubercular activity with a MIC of 3.125 μg/mL. A p-substituted phenyl group (p-tolyl or p-chlorophenyl) in the imidazo[2,1-b][1,3,4]thiadiazole ring and/or a chloro group in the benzimidazole ring enhance anti-tuberculosis activity whereas a nitro group in the benzimidazole ring reduces the activity. In the antibacterial screening, compounds 5i, 5w and 5ac showed promising activity against the tested bacterial strains. Further, antifungal and antioxidant activities of these molecules were also investigated. In the cytotoxicity study, the active antitubercular compounds exhibited very low toxicity against a normal cell line.

  16. Synthesis, Characterization and Anti-Inflammatory Activity of Some 1, 3,4 -Oxadiazole Derivatives

    PubMed Central

    Kumar Singh, Arvind; Lohani, M; Parthsarthy, R

    2013-01-01

    A series of five-membered heterocyclic rings were synthesized by the reaction between benzoyl chloride and various chlolro-nitro-benzoyl chlorides and semi carbazide to form (C1- C7) compounds and was tested for their anti-inflammatory activity determined by rat-paw-oedema method. All the synthesis compounds have been characterized by 1HNMR, IR and Mass spectral data. The compounds were purified by column chromatography. All synthesized derivatives were determined by the carrageenan-induced rat-paw-oedema model for anti-inflammatory activity. The entire compound gives good response for the anti-inflammatory activity: [3-Chloro-N-[5-(3-Chloro-phenyl)-[1,3,4] oxadiazole-2yl] benzamide (C4), and [4-Nitro-N-[5-(4-Nitro-phenyl)-[1,3,4] oxadiazole-2yl] benzamide (C7). For this activity, indometacin was used as a standard drug and compared to new synthesized drugs. Some new synthesized drugs have shown better activities for the anti-inflammation. PMID:24250606

  17. Biodegradation of 1,2,3- and 1,2,4-Trichlorobenzene in Soil and in Liquid Enrichment Culture †

    PubMed Central

    Marinucci, A. C.; Bartha, R.

    1979-01-01

    The biodegradation of radiochemically pure (99%) 1,2,3- and 1,2,4-trichlorobenzene (TCB) in soil was investigated. Experimental difficulties posed by the high volatility and slow biodegradation rate of the TCBs were partially overcome by using a specially designed incubation and trapping apparatus. Evolution of 14CO2 from active versus poisoned soil dosed with 50 μg of the individual TCBs per g gave conclusive proof that both isomers are biodegradable. At 20°C, 1,2,4-TCB was mineralized at an approximate rate of 1 nmol/day per 20 g of soil sample, and 1,2,3-TCB was mineralized at one-half to one-third that rate. Mineral fertilizers or cosubstrates failed to increase TCB mineralization rates in soil. Anaerobic conditions had a negative effect on mineralization, and increased temperatures had a positive effect. With increasing 1,2,4-TCB concentrations, 14CO2 evolution exhibited saturation kinetics with an apparent Km of 55.5 nmol per g of soil. Recovery of total radioactivity was good from soil containing high organic matter concentrations. From low-organic-matter soil, some of the radioactivity was recovered only on combustion, and overall recovery was lower. In soil-inoculated liquid culture, the cosubstrates glucose and benzene caused a slight stimulation of 1,2,4-TCB mineralization. Cochromatography of known standards with the extracts of soil pretreated with [14C]TCBs indicated that 3,4,5-trichlorophenol, 2,6-dichlorophenol and, to a lesser degree, 2,3-dichlorophenol were present in soils incubated with 1,2,3-TCB. 2,4-, 2,5-, and 3,4-dichlorophenol were present in soils incubated with 1,2,4-TCB. PMID:120698

  18. TLR4-dependent internalization of CX3CR1 aggravates sepsis-induced immunoparalysis

    PubMed Central

    Ge, Xin-Yu; Fang, Shang-Ping; Zhou, Miao; Luo, Jing; Wei, Juan; Wen, Xue-Ping; Yan, Xiao-Di; Zou, Zui

    2016-01-01

    Sepsis, the most severe manifestation of infection, poses a major challenge to health-care systems around the world. Limited ability to clean and remove the pathogen renders difficulty in septic patients to recover from the phase of immunoparalysis. The present study found the vital role of CX3CR1 internalization on sepsis-induced immunoparalysis. A mouse model with cecal ligation and puncture (CLP) and cell model with lipopolysaccharides (LPS) were employed to explore the relationship between CX3CR1 internalization and septic immunoparalysis. Immunoparalysis model in mice was established 4 days after CLP with significantly decreased proinflammatory cytokines. Flow cytometry analysis found a decreased surface expression of CX3CR1 during immunoparalysis, which was associated with reduced mRNA level and increased internalization of CX3CR1. G-protein coupled receptor kinase 2 (GRK2) and β-arrestin2 were significantly increased during septic immunoparalysis and involved in the internalization of CX3CR1. TLR4-/- or TLR4 inhibitor-treated macrophages exhibited an inhibited expression of GRK2 and β-arrestin2, along with reduced internalization of CX3CR1. Moreover, the knockdown of GRK2 and β-arrestin2 inhibited the internalization of CX3CR1 and led to a higher response on the second hit, which was associated with an increased activation of NF-κB. The critical association between internalization of CX3CR1 and immunosuppression in sepsis may provide a novel reference for clinical therapeutics. PMID:28078040

  19. TLR4-dependent internalization of CX3CR1 aggravates sepsis-induced immunoparalysis.

    PubMed

    Ge, Xin-Yu; Fang, Shang-Ping; Zhou, Miao; Luo, Jing; Wei, Juan; Wen, Xue-Ping; Yan, Xiao-Di; Zou, Zui

    2016-01-01

    Sepsis, the most severe manifestation of infection, poses a major challenge to health-care systems around the world. Limited ability to clean and remove the pathogen renders difficulty in septic patients to recover from the phase of immunoparalysis. The present study found the vital role of CX3CR1 internalization on sepsis-induced immunoparalysis. A mouse model with cecal ligation and puncture (CLP) and cell model with lipopolysaccharides (LPS) were employed to explore the relationship between CX3CR1 internalization and septic immunoparalysis. Immunoparalysis model in mice was established 4 days after CLP with significantly decreased proinflammatory cytokines. Flow cytometry analysis found a decreased surface expression of CX3CR1 during immunoparalysis, which was associated with reduced mRNA level and increased internalization of CX3CR1. G-protein coupled receptor kinase 2 (GRK2) and β-arrestin2 were significantly increased during septic immunoparalysis and involved in the internalization of CX3CR1. TLR4(-/-) or TLR4 inhibitor-treated macrophages exhibited an inhibited expression of GRK2 and β-arrestin2, along with reduced internalization of CX3CR1. Moreover, the knockdown of GRK2 and β-arrestin2 inhibited the internalization of CX3CR1 and led to a higher response on the second hit, which was associated with an increased activation of NF-κB. The critical association between internalization of CX3CR1 and immunosuppression in sepsis may provide a novel reference for clinical therapeutics.

  20. 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.

  1. CDK4/6-dependent activation of DUB3 regulates cancer metastasis through SNAIL1.

    PubMed

    Liu, Tongzheng; Yu, Jia; Deng, Min; Yin, Yujiao; Zhang, Haoxing; Luo, Kuntian; Qin, Bo; Li, Yunhui; Wu, Chenming; Ren, Tao; Han, Yang; Yin, Peng; Kim, JungJin; Lee, SeungBaek; Lin, Jing; Zhang, Lizhi; Zhang, Jun; Nowsheen, Somaira; Wang, Liewei; Boughey, Judy; Goetz, Matthew P; Yuan, Jian; Lou, Zhenkun

    2017-01-09

    Tumour metastasis, the spread of cancer cells from the original tumour site followed by growth of secondary tumours at distant organs, is the primary cause of cancer-related deaths and remains poorly understood. Here we demonstrate that inhibition of CDK4/6 blocks breast tumour metastasis in the triple-negative breast cancer model, without affecting tumour growth. Mechanistically, we identify a deubiquitinase, DUB3, as a target of CDK4/6; CDK4/6-mediated activation of DUB3 is essential to deubiquitinate and stabilize SNAIL1, a key factor promoting epithelial-mesenchymal transition and breast cancer metastasis. Overall, our study establishes the CDK4/6-DUB3 axis as an important regulatory mechanism of breast cancer metastasis and provides a rationale for potential therapeutic interventions in the treatment of breast cancer metastasis.

  2. CDK4/6-dependent activation of DUB3 regulates cancer metastasis through SNAIL1

    PubMed Central

    Liu, Tongzheng; Yu, Jia; Deng, Min; Yin, Yujiao; Zhang, Haoxing; Luo, Kuntian; Qin, Bo; Li, Yunhui; Wu, Chenming; Ren, Tao; Han, Yang; Yin, Peng; Kim, JungJin; Lee, SeungBaek; Lin, Jing; Zhang, Lizhi; Zhang, Jun; Nowsheen, Somaira; Wang, Liewei; Boughey, Judy; Goetz, Matthew P.; Yuan, Jian; Lou, Zhenkun

    2017-01-01

    Tumour metastasis, the spread of cancer cells from the original tumour site followed by growth of secondary tumours at distant organs, is the primary cause of cancer-related deaths and remains poorly understood. Here we demonstrate that inhibition of CDK4/6 blocks breast tumour metastasis in the triple-negative breast cancer model, without affecting tumour growth. Mechanistically, we identify a deubiquitinase, DUB3, as a target of CDK4/6; CDK4/6-mediated activation of DUB3 is essential to deubiquitinate and stabilize SNAIL1, a key factor promoting epithelial–mesenchymal transition and breast cancer metastasis. Overall, our study establishes the CDK4/6–DUB3 axis as an important regulatory mechanism of breast cancer metastasis and provides a rationale for potential therapeutic interventions in the treatment of breast cancer metastasis. PMID:28067227

  3. 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].

  4. Synthesis and anti-inflammatory activity evaluation of a novel series of 6-phenoxy-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide derivatives.

    PubMed

    Liu, Da-Chuan; Gong, Guo-Hua; Wei, Cheng-Xi; Jin, Xue-Jun; Quan, Zhe-Shan

    2016-03-15

    The transcription factor nuclear factor-κB (NF-κB) controls many physiological processes including inflammation, immunity, and apoptosis. In this study, a novel series of 6-phenoxy-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide derivatives were synthesized as potent anti-inflammatory agents, which acted on tumor necrosis factor (TNF-α) as inhibitors of NF-κB activation. We showed that compounds 6h (6-(2,4-dichlorophenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide) and 6i (6-(3-tolyloxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide) showed more prominent anti-inflammatory activity than other compounds, with similar activities as the reference drug dihydrotanshinone; compound 6i showed the lowest cellular toxicity among the tested compounds. In vivo evaluation of the anti-inflammatory activity showed that compound 6i exhibited excellent anti-inflammatory activity with 58.19% inhibition at 50mg/kg intraperitoneal (i.p.), with equal efficacy as the positive control indomethacin (100mg/kg i.p.; 59.21% inhibition).

  5. Palladium-catalyzed heteroannulation leading to heterocyclic structures with two heteroatoms: a highly regio- and stereoselective synthesis of (Z)-4-alkyl-2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzoxazines and (Z)-3-alkyl(aryl)idene-4-tosyl-3,4-dihydro-2H-1,4-benzoxazines.

    PubMed

    Kundu, N G; Chaudhuri, G; Upadhyay, A

    2001-01-12

    A highly convenient method has been developed for the synthesis of (Z)-4-alkyl-2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzoxazines 9 and (Z)-3-alkyl(aryl)idene-4-tosyl-3,4-dihydro-2H-1,4-benzoxazines 34-38 through palladium-copper-catalyzed reactions. Aryl halides 7 reacted with 2-[N-alkyl(benzyl)-N-prop-2'-ynyl]aminophenyl tosylate 6 in the presence of (PPh3)2PdCl2 (3 mol %), CuI(5 mol %) in triethylamine at room temperature to yield 2-[N-alkyl(benzyl)-N-(3-aryl-prop-2'-ynyl)]-aminophenyl tosylates 8 in extremely good yields (72-96%). The latter could then be cyclized with KOH in ethanol-water to Z-9 in a highly regio- and stereoselective manner. Similarly, palladium-copper-catalyzed reaction of 2-(prop-2'-ynyloxy)aniline (21) with aryl iodides 7 led to 22-26 which after tosylation and cyclization with cuprous iodide in CH3CN in the presence of K2CO3 and Bu4-NBr led to the (Z)-3-alkyl(aryl)idene-4-tosyl 3,4-dihydro-2H-1,4-benzoxazines 34-38 in good overall yields. The Z-stereochemistry of the products was established from 1H NMR spectra, 3JCH values (between vinylic proton and methylenic carbon of the heterocyclic ring), NOE experiments, and X-ray analysis. The method was also found to be suitable for the synthesis of bis(benzoxazinylated) derivatives 17, 39, and 2-alkyl-3,4-dihydro-2H-1,4-benzoxazines 18. Our method for the synthesis of 3,4-dihydro-2H-1,4-benzoxazines is highly efficacious, using easily available starting materials under very mild conditions. Also the synthesis of some novel 5-substituted uracil derivatives 40 and 41 containing the benzoxazinyl moiety and of potential biological interest is being reported.

  6. Efficient π-electron conjugated push-pull nonlinear optical chromophore 1-(4-methoxyphenyl)-3-(3,4-dimethoxyphenyl)-2-propen-1-one: A vibrational spectral study

    NASA Astrophysics Data System (ADS)

    Abraham, Jose P.; Sajan, D.; Shettigar, Venkataraya; Dharmaprakash, S. M.; Němec, I.; Hubert Joe, I.; Jayakumar, V. S.

    2009-01-01

    As part of the efforts for the design new organic nonlinear optical (NLO) materials with high efficiency for present day technological requirements, a comprehensive investigation on the intramolecular charge transfer (ICT) of an efficient π-conjugated potential push-pull NLO chromophore, 1-(4-methoxyphenyl)-3-(3,4-dimethoxyphenyl)-2-propen-1-one to a strong electron acceptor group through the π-conjugated bridge has been carried out from their vibrational spectra. The NIR FT-Raman and FT-IR spectra supported by the density functional theory (DFT) quantum chemical computations have been employed to analyze the effects of intramolecular charge transfer on the geometries and the vibrational modes contributing to the linear electro-optic effect of the organic NLO material. The calculated first hyperpolarizability of DMMC is 6.650 × 10 -30 esu, which is 25 times that of urea. The simultaneous IR and Raman activation of the phenyl ring modes of ν(C dbnd C/C-C) mode, ring C dbnd C stretching modes, in-plane deformation modes and the umbrella mode of methyl groups also provide evidences for the charge transfer interaction between the donors and the acceptor group through the π-system. Vibrational analysis indicates the electronic effects such as induction and back-donation on the methyl hydrogen atoms causing the lowering of stretching wavenumbers have also been analyzed in detail. The planar conformations would give an enhanced NLO activity where as any deviations from planarity would decrease the mobility of electrons within the π-conjugated molecular system, resulting a reduction in NLO activity.

  7. A role for Rab14 in the endocytic trafficking of GLUT4 in 3T3-L1 adipocytes.

    PubMed

    Reed, Sam E; Hodgson, Lorna R; Song, Shuang; May, Margaret T; Kelly, Eoin E; McCaffrey, Mary W; Mastick, Cynthia C; Verkade, Paul; Tavaré, Jeremy M

    2013-05-01

    Insulin enhances the uptake of glucose into adipocytes and muscle cells by promoting the redistribution of the glucose transporter isoform 4 (GLUT4) from intracellular compartments to the cell surface. Rab GTPases regulate the trafficking itinerary of GLUT4 and several have been found on immunopurified GLUT4 vesicles. Specifically, Rab14 has previously been implicated in GLUT4 trafficking in muscle although its role, if any, in adipocytes is poorly understood. Analysis of 3T3-L1 adipocytes using confocal microscopy demonstrated that endogenous GLUT4 and endogenous Rab14 exhibited a partial colocalisation. However, when wild-type Rab14 or a constitutively-active Rab14Q70L mutant were overexpressed in these cells, the colocalisation with both GLUT4 and IRAP became extensive. Interestingly, this colocalisation was restricted to enlarged 'ring-like' vesicular structures (mean diameter 1.3 µm), which were observed in the presence of overexpressed wild-type Rab14 and Rab14Q70L, but not an inactive Rab14S25N mutant. These enlarged vesicles contained markers of early endosomes and were rapidly filled by GLUT4 and transferrin undergoing endocytosis from the plasma membrane. The Rab14Q70L mutant reduced basal and insulin-stimulated cell surface GLUT4 levels, probably by retaining GLUT4 in an insulin-insensitive early endosomal compartment. Furthermore, shRNA-mediated depletion of Rab14 inhibited the transit of GLUT4 through early endosomal compartments towards vesicles and tubules in the perinuclear region. Given the previously reported role of Rab14 in trafficking between endosomes and the Golgi complex, we propose that the primary role of Rab14 in GLUT4 trafficking is to control the transit of internalised GLUT4 from early endosomes into the Golgi complex, rather than direct GLUT4 translocation to the plasma membrane.

  8. Probes for narcotic receptor mediated phenomena. 40.1 N-Substituted cis-4a-ethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-8-ols

    PubMed Central

    Iyer, Malliga R.; Lee, Yong Sok; Deschamps, Jeffrey R.; Rothman, Richard B.; Dersch, Christina M.; Jacobson, Arthur E.; Rice, Kenner C.

    2009-01-01

    A series of N-substituted rac-cis-4a-ethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-8-ols have been prepared using a simple synthetic route previously designed for synthesis of related cis-2-methyl-4a-alkyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols. The new phenolic compounds, where the aromatic hydroxy moiety is situated ortho to the oxygen atom in the oxide-bridged ring, do not interact as well as the pyridin-6-ols with opioid receptors. The N-para-fluorophenethyl derivative had the highest μ-opioid receptor affinity of the examined compounds (Ki = 0.35 μM). PMID:20005115

  9. Detection of a novel neurotoxic metabolite of Parkinson's disease-related neurotoxin, 1-benzyl-1,2,3,4- tetrahydroisoquinoline.

    PubMed

    Kotake, Yaichiro; Sekiya, Yoko; Okuda, Katsuhiro; Ohta, Shigeru

    2014-01-01

    Naturally occurring low-molecular weight compounds with a chemical structure like that of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, such as 1-benzyl-1,2,3,4-tetrahydroisoquinoline(1BnTIQ), are candidates for the endogenous neurotoxins that cause Parkinson's disease (PD). 1BnTIQ is an endogenous amine in human CSF and increases in the CSF of patients with PD. It inhibits complex Iand elicits PD-like behavioral abnormalities in monkey and mouse. In this study, we searched metabolites of 1BnTIQ by rat liver S9 using liquid chromatography-tandem mass spectrometry, and identified a dehydrated metabolite, 1-benzyl-3,4-dihydroisoquinoline (1BnDIQ). 1BnDIQ was identified by corresponding mass spectra and precursor ion scans in authentic and complete enzyme samples. Multiple reaction monitoring analysis showed microsome-dependent 1BnDIQ production. We previously reported that 1BnDIQ is more toxic than 1BnTIQ in cytotoxicity study in SH-SY5Y neuroblastoma cells. In addition, 1BnTIQ is reported to pass through the blood-brain barrier of the rat brain, and 1BnDIQ is supposed to be more lipophilic than 1BnTIQ. 1BnDIQ may easily reach the brain, and it might contribute to PD-related neurotoxicity.

  10. [mu-3,4'-Bi-1,2,4-triazole-di-micro-chloro-copper(II) monohydrate].

    PubMed

    Guédira, Fouzia; Idrissi, Malika Saidi; Krautscheid, Harald; El Ammari, Lahcen

    2003-12-01

    In the title compound, mu-3,4'-bi-1,2,4-triazole-di-mu-chloro-copper(II) monohydrate, [[CuCl(2)(C(4)H(4)N(6))].H(2)O](n), the Cu atom is located in a distorted octahedron consisting of two N atoms and four Cl atoms. The structural unit is an infinite chain in which octahedral groups, connected by shared edges, are also linked by bitriazole molecules. The bitriazole ligand, the Cu atom and the water O atom all lie on independent twofold axes. The structure is held together by hydrogen bonds between the water molecules and the non-coordinated N atoms of the ligand, and by van der Waals forces.

  11. 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

  12. Extensive metabolic activation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in smokers

    PubMed Central

    Stepanov, Irina; Upadhyaya, Pramod; Carmella, Steven G.; Feuer, Rachel; Jensen, Joni; Hatsukami, Dorothy K.; Hecht, Stephen S.

    2008-01-01

    4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent lung carcinogen present in both unburned tobacco and cigarette smoke. The sum of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides, referred to as total NNAL, is an established urinary biomarker of human NNK uptake. Metabolic activation of NNK to DNA adducts proceeds via α-hydroxylation pathways, and 4-oxo-4-(3-pyridyl)butanoic acid (keto acid) and 4-hydroxy-4-(3-pyridyl)butanoic acid (hydroxy acid) are the principal end products of these pathways in rodents and primates. The purpose of this study was to determine NNK metabolic activation in smokers, as measured by the sum of keto acid and hydroxy acid, relative to total NNAL. To specifically identify NNK-derived keto acid and hydroxy acid, which are also formed extensively from nicotine, we added [pyridine-D4]NNK to cigarettes that were originally low in NNK, and measured the deuterium-labeled metabolites in the urine of people who smoked these cigarettes. The total amount of [pyridine-D4]keto acid plus [pyridine-D4]hydroxy acid averaged 4.00±2.49 nmol/24 h, while the average amount of total [pyridine-D4]NNAL was 0.511±0.368 nmol/24 h. The results of this study demonstrate for the first time that NNK metabolic activation is a quantitatively significant pathway in smokers, accounting for about 86% of total urinary excretion of NNK metabolites. The large interindividual variation in the excreted [pyridine-D4]keto acid and [pyridine-D4]hydroxy acid among 20 smokers strongly support our hypothesis that some smokers activate NNK more extensively than others, and that the ratio between biomarkers of metabolic activation and detoxification at a given dose of NNK could be a potential indicator of cancer risk. PMID:18628430

  13. Phase diagram for Bi1-xCaxMnO3 (x < 0.4)

    NASA Astrophysics Data System (ADS)

    Qin, Yuhai; Tyson, Trevor; Cheong, Sang-Wook; Xu, Xiao-Nong

    2008-03-01

    The multiferroic BiMnO3 system, in which ferroelectronic and ferromagnetic orders can coexist, has attracted much research work in the past years for its potential technological applications. For the more general system Bi1-xCaxMnO3, the phase diagram for the Ca rich region (x > 0.4) has been established[1]. In order to understand the multiferroic behavior near the x=0 system, the hole-doped region (04) was investigated. We have completed the magnetic, transport, and structural phase diagram of Bi1-xCaxMnO3, by performing detailed structural (XRD and XAFS), magnetization (ZFC/FC) and electrical measurements on Bi1-xCaxMnO3 (04), showing the transition form the highly distorted monoclinic phase to the orthorhombic phase. This work is supported by NSF DMR-0512196 and DOE Grant DE-FG02-07ER46402. [1] H. Woo, et al, Phys. Rev. B: Condensed Matter and Materials Physics 63, 134412/1 (2001).

  14. 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

  15. Molecular structure, interatomic interactions and vibrational analysis of 1,4-diazabicyclo[3.2.1]octane parent ring system

    NASA Astrophysics Data System (ADS)

    Britvin, Sergey N.; Rumyantsev, Andrey M.; Zobnina, Anastasia E.; Padkina, Marina V.

    2017-02-01

    Molecular structure of 1,4-diazabicyclo[3.2.1]octane, a parent ring of TAN1251 family of alkaloids, is herein characterized for the first time in comparison with the structure of nortropane (8-azabicyclo[3.2.1]octane), the parent framework of tropane ring system. The methods of study involve X-ray structural analysis, DFT geometry optimizations with infrared frequency calculations followed by natural bond orbital (NBO) analysis, and vibrational analysis of infrared spectrum.

  16. 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

    2016-04-07

    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).

  17. 3. REAR OF NORTH PORTAL TUNNEL NO.4. PART 1 OF ...

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

    3. REAR OF NORTH PORTAL TUNNEL NO.4. PART 1 OF 2 PART PANORAMA WITH PHOTOGRAPH CA-265-G-2-b. NOTE CONSTRUCTION MATERIALS FOR FREEWAY WIDENING OF HILL STREET EXIT. LOOKING 2°N. - Figueroa Street Tunnels, Mileposts 24.90, 25.14, 25.28, & 25.37 on Arroyo Seco Parkway, Los Angeles, Los Angeles County, CA

  18. 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…

  19. Synthesis and derivatisation of a novel spiro[1-benzofuran-2,4'-piperidin]-3-one scaffold.

    PubMed

    Wilson, Rowan A; Chan, Lai; Wood, Robin; Brown, Richard C D

    2005-09-07

    The synthesis of a novel spiro[1-benzofuran-2,4'-piperidin]-3-one scaffold has been achieved in five steps with an overall yield of 47%. The versatility of the spiropiperidine scaffold in the context of library synthesis is exemplified by selective and sequential derivatisation of the amino and aryl bromide functional groups, including the development of multi-step telescope reaction matrices.

  20. 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.

  1. (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.

  2. 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......

  3. Aquatic Toxicity of 3-Nitro-1,2,4-Triazol-5-One

    DTIC Science & Technology

    2009-09-01

    Ceriodaphnia dubia in a 7 day survival and reproduction assay and the unicellular green algae Selenastrum capricornutum in a 96 hr growth inhibition...Distilled Water 8 2.1.3 Analytical Methods 8 2.2 NTO Stability Testing 8 2.3 Ceriodaphnia 7 Day Survival and Reproduction Assay 8 2.4 Algal Growth...of each concentration were placed into amber crimper vials, capped, then stored under Ceriodaphnia 7 day Survival and Reproduction test conditions

  4. A luminescent Eu(III) complex based on 2-(4', 4', 4'-trifluoro-1', 3'-dioxobutyl)-dibenzothiophene for light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Liu, Sheng-Gui; Gong, Meng-Lian; Wang, Sheng; Tan, Xiu-Mei

    2009-10-01

    Complex Eu(dbt) 3(phen) (Hdbt = 2-(4', 4', 4'-trifluoro-1', 3'-dioxobutyl)-dibenzothiophene, phen = 1,10-phenanthroline) was synthesized. The complex emits red luminescence, characteristic of the 5D0 → 7FJ ( J = 0-4) emission bands of Eu 3+ under near ultraviolet. A red conversion light-emitting diode (LED) device was fabricated by coating complex onto InGaN-based-LED chip that emits 395 nm ultraviolet light. When the mass ratio of the red phosphor to the silicone is 1:25, the LED device's CIE chromaticity coordinates are x = 0.5835, y = 0.2857, and the luminescence efficiency is 1.29 lm/w. All the results show that this europium complex may act as a red component in fabrication of white LEDs with high color-rendering index.

  5. A luminescent Eu(III) complex based on 2-(4', 4', 4'-trifluoro-1', 3'-dioxobutyl)-dibenzothiophene for light-emitting diodes.

    PubMed

    Liu, Sheng-Gui; Gong, Meng-Lian; Wang, Sheng; Tan, Xiu-Mei

    2009-10-15

    Complex Eu(dbt)(3)(phen) (Hdbt=2-(4', 4', 4'-trifluoro-1', 3'-dioxobutyl)-dibenzothiophene, phen=1,10-phenanthroline) was synthesized. The complex emits red luminescence, characteristic of the (5)D(0)-->(7)F(J) (J=0-4) emission bands of Eu(3+) under near ultraviolet. A red conversion light-emitting diode (LED) device was fabricated by coating complex onto InGaN-based-LED chip that emits 395nm ultraviolet light. When the mass ratio of the red phosphor to the silicone is 1:25, the LED device's CIE chromaticity coordinates are x=0.5835, y=0.2857, and the luminescence efficiency is 1.29 lm/w. All the results show that this europium complex may act as a red component in fabrication of white LEDs with high color-rendering index.

  6. 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.

  7. (2R,3S,4R)-3,4-Isopropyl­idenedi­oxy-2-(phenyl­sulfonyl­meth­yl)pyrrolidin-1-ol

    PubMed Central

    Flores, Mari Fe; Garcia, Pilar; M. Garrido, Narciso; Sanz, Francisca; Diez, David

    2012-01-01

    The title compound, C14H19NO5S, was prepared by nucleophilic addition of the lithium derivative of methyl­phenyl­sulfone to (3S,4R)-3,4-isopropyl­idene­dioxy­pyrroline 1-oxide. There are four mol­ecules in the asymmetric unit. The crystal structure determination confirms the configuration of the chiral centres as 2R,3S,4R. In the crystal, pairs of O—H⋯N hydrogen bonds link the mol­ecules into dimers. PMID:22904989

  8. Knockdown of NYGGF4 (PID1) rescues insulin resistance and mitochondrial dysfunction induced by FCCP in 3T3-L1 adipocytes.

    PubMed

    Shi, Chun-Mei; Wang, Yu-Mei; Zhang, Chun-Mei; Qiu, Jie; Shen, Ya-Hui; Zhu, Jin-Gai; Chen, Lin; Xu, Guang-Feng; Zhao, Ya-Ping; Ji, Chen-Bo; Guo, Xi-Rong

    2012-11-01

    NYGGF4 is a recently identified gene that is involved in obesity-associated insulin resistance. Previous data from this laboratory have demonstrated that NYGGF4 overexpression might contribute to the development of insulin resistance (IR) and to mitochondrial dysfunction. Additionally, NYGGF4 knockdown enhanced insulin sensitivity and mitochondrial function in 3T3-L1 adipocytes. We designed this study to determine whether silencing of NYGGF4 in 3T3-L1 adipocytes could rescue the effect of insulin sensitivity and mitochondrial function induced by the cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP), a mitochondrion uncoupler, to ascertain further the mechanism of NYGGF4 involvement in obesity-associated insulin resistance. We found that 3T3-L1 adipocytes, incubated with 5μM FCCP for 12h, had decreased levels of insulin-stimulated glucose uptake and had impaired insulin-stimulated GLUT4 translocation. Silencing also diminished insulin-stimulated tyrosinephosphorylation of IRS-1 and serine phosphorylation of Akt. This phenomenon contrasts with the effect of NYGGF4 knockdown on insulin sensitivity and describes the regulatory function of NYGGF4 in adipocytes insulin sensitivity. We next analyzed the mitochondrial function in NYGGF4-silenced adipocytes incubated with FCCP. NYGGF4 knockdown partly rescued the dissipation of mitochondrial mass, mitochondrial DNA, intracellular ATP synthesis, and intracellular reactive oxygen species (ROS) production occurred following the addition of FCCP, as well as inhibition of mitochondrial transmembrane potential (ΔΨm) in 3T3-L1 adipocytes incubated with FCCP. Collectively, our results suggested that addition of silencing NYGGF4 partly rescued the effect of insulin resistance and mitochondrial dysfunction in NYGGF4 silenced 3T3-L1 adipocytes incubated with FCCP, which might explain the involvement of NYGGF4-induced IR and the development of NYGGF4 in mitochondrial function.

  9. Experimental and theoretical investigations of spectroscopic properties of 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine

    NASA Astrophysics Data System (ADS)

    Muthu, S.; Prasath, M.; Arun Balaji, R.

    2013-04-01

    The Fourier transform infrared (FTIR) and FT-Raman spectra of 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine (8C1M6PB) have been recorded in the range of 4000-400 and 4000-100 cm-1, respectively. A detailed interpretation of the vibrational spectra of this compound has been made on the basis of the calculated potential energy distribution (PED). The equilibrium geometries, harmonic frequencies, infrared intensities and Raman scattering activities were calculated by Hartree-Fock (HF) and density functional B3LYP method with the 6-31G (d,p) basis set. The vibrational frequencies were calculated in all these methods and were compared with the experimental frequencies which yield good agreement between observed and calculated frequencies. The first order hyperpolarizability (βtotal) of this molecular system and related properties (β, μ, and Δα) are calculated using HF/6-31G (d,p) and B3LYP/6-31G(d,p) methods based on the finite-field approach. The calculated Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) energies show that charge transfer occurs in the molecule. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. Conformation analysis was carried for 8C1M6PB by Potential energy surface scan to find all possible conformers with B3LYP method using 6-31G (d,p) basis set. The entropy of the title compound is also performed at HF/6-31G (d,p) and B3LYP/6-31G(d,p) levels of theory. In addition, the thermodynamic properties of the compound were calculated at different temperatures and corresponding relations between the properties and temperature were also studied.

  10. Determination of 3-amino-1,2,4-triazole (amitrole) in environmental waters by capillary electrophoresis.

    PubMed

    Chicharro, M; Zapardiel, A; Bermejo, E; Moreno, M

    2003-01-02

    3-Amino-1,2,4-triazole (amitrole) is a widely used pesticide, with many difficulties to be analyzed at the regulatory level in drinking water, because its high solubility in water. This paper describes a simple and fast method for the simultaneous determination of amitrole and atrazin-2-hydroxy, principal degradation product of s-triazines, by capillary zone electrophoresis. Separation and determination of these herbicides in water samples was performed in 0.02 mol l(-1) phosphate buffer at pH 3.2. The method allows determination of the amitrole and atrazin-2-hydroxy in water samples in concentration lower than 100 mug l(-1). The detection limits using a previous preconcentration step of amitrole in Alberche River (Comunidad Autónoma de Madrid, Spain) and drinking water spiked samples was of 4 mug l(-1).

  11. Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1

    PubMed Central

    Manka, Jason T.; Rodriguez, Alice L.; Morrison, Ryan D.; Venable, Daryl F.; Cho, Hyekyung P.; Blobaum, Anna L.; Daniels, J. Scott; Niswender, Colleen M.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A.

    2014-01-01

    Development of SAR in an octahydropyrrolo[3,4-c]pyrrole series of negative allosteric modulators of mGlu1 using a functional cell-based assay is described in this Letter. The octahydropyrrolo[3,4-c]pyrrole scaffold was chosen as an isosteric replacement for the piperazine ring found in the initial hit compound. Characterization of selected compounds in protein binding assays was used to identify the most promising analogs, which were then profiled in P450 inhibition assays in order to further assess the potential for drug-likeness within this series of compounds. PMID:23932792

  12. 1,2,3,4-bis(p-methylbenzylidene sorbitol) accelerates crystallization and improves hole mobility of poly(3-hexylthiophene)

    NASA Astrophysics Data System (ADS)

    Yuan, Nana; Huo, Hong

    2016-02-01

    The addition of 1,2,3,4-bis(p-methylbenzylidene sorbitol) (MDBS) does not change the nucleation mechanism or the crystal form of poly(3-hexylthiophene) (P3HT), but its presence increases the crystallization temperature (T c) of P3HT, decreases the crystallization half-time (t 1/2) and accelerates P3HT crystallization, which indicates that MDBS is an effective nucleating agent for P3HT. An acceleration of P3HT crystallization by the addition of MDBS decreases the crystalline size and crystallinity of P3HT, and enhances the connectivity between ordered regions of P3HT, leading to the hole mobility rising from 1.99 × 10-6 to 7.57 × 10-5 cm2 V-1s-1 in P3HT:PCBM blend based hole-only devices with sandwich configurations. Our results suggest that accelerating P3HT crystallization by adding a nucleating agent might be an important factor to improve the hole mobility and balance the electron and hole mobility in a photovoltaic blend.

  13. 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…

  14. Characterization of Hydrazinium 3,5-Dinitroamine-1,2,4-triazole

    NASA Astrophysics Data System (ADS)

    Cui, Kejian; Meng, Zihui; Xu, Zhibin; Xue, Min; Lin, Zhihui; Wang, Bozhou; Ge, Zhongxue; Qin, Guangmin

    2014-05-01

    The structure of hydrazinium 3,5-dinitroamine-1,2,4-triazole (HDNAT) was investigated with infrared (IR), mass spectrometry, 13C-NMR, scanning electron microscopy (SEM), and X-ray crystallography. The crystal density of HDNAT was determined as 1.91 g/cm3 using X-ray diffraction. The crystal belongs to a monoclinic system with the space group P2(1). The thermal decomposition process of HDNAT was investigated via thermogravimetry-differential thermal analysis (TG-DTA) at a heating rate of 10 K/min and differential scanning calorimetry (DSC) under nonisothermal conditions. The decomposition kinetic and thermodynamic parameters were obtained by the Kissinger and Ozawa method. HDNAT can be analyzed by using a C18 high-performance liquid chromatography (HPLC) column with water : acetonitrile : trifluoroacetic acid (97/3/0.1, v/v/v) as the mobile phase and a capacity factor of 1.33.

  15. Effect of DNA methylation profile on OATP3A1 and OATP4A1 transcript levels in colorectal cancer.

    PubMed

    Rawłuszko-Wieczorek, Agnieszka Anna; Horst, Nikodem; Horbacka, Karolina; Bandura, Artur Szymon; Świderska, Monika; Krokowicz, Piotr; Jagodziński, Paweł Piotr

    2015-08-01

    Epidemiological studies indicate that 17β-estradiol (E2) prevents colorectal cancer (CRC). Organic anion transporting polypeptides (OATPs) are involved in the cellular uptake of various endogenous and exogenous substrates, including hormone conjugates. Because transfer of estrone sulfate (E1-S) can contribute to intra-tissue conversion of estrone to the biologically active form -E2, it is evident that the expression patterns of OATPs may be relevant to the analysis of CRC incidence and therapy. We therefore evaluated DNA methylation and transcript levels of two members of the OATP family, OATP3A1 and OATP4A1, that may be involved in E1-S transport in colorectal cancer patients. We detected a significant reduction in OATP3A1 and a significant increase in OATP4A1 mRNA levels in cancerous tissue, compared with histopathologically unchanged tissue (n=103). Moreover, we observed DNA hypermethylation in the OATP3A1 promoter region in a small subset of CRC patients and in HCT116 and Caco-2 colorectal cancer cell lines. We also observed increased OATP3A1 transcript following treatment with 5-aza-2-deoxycytidine and sodium butyrate. The OATP4A1 promoter region was hypomethylated in analyzed tissues and CRC cell lines and was not affected by these treatments. Our results suggest a potential mechanism for OATP3A1 downregulation that involves DNA methylation during colorectal carcinogenesis.

  16. (3E,5E)-3,5-Bis(4-methyl-benzyl-idene)-1-[3-(piperidin-1-yl)propano-yl]piperidin-4-one.

    PubMed

    Kia, Yalda; Osman, Hasnah; Murugaiyah, Vikneswaran; Arshad, Suhana; Razak, Ibrahim Abdul

    2012-08-01

    In the title compound, C(29)H(34)N(2)O(2), the central piperidine ring adopts a half-chair conformation, whereas the terminal one adopts a chair conformation. The mean plane of the central piperidine ring [maximum deviation = 0.384 (2) Å] makes dihedral angles of 64.82 (13) and 17.55 (13)° with the benzene rings. In the crystal, mol-ecules are linked into a tape along the b axis via C-H⋯O inter-actions, generating R(2) (2)(20) and R(2) (1)(6) graph-set motifs. C-H⋯π inter-actions are observed between the tapes.

  17. 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.

  18. Synthesis, Characterization and Screening for Analgesic and Anti-inflammatory activities of 2, 5-disubstituted 1, 3, 4-oxadiazole derivatives.

    PubMed

    Dewangan, Dhansay; Nakhate, Kartik T; Tripathi, D K; Kashyap, Pranita; Dhongde, Hemant

    2015-01-01

    The aim of the present investigation was to synthesize, characterize and evaluate analgesic and anti- inflammatory activities of 2, 5-disubstituted 1, 3, 4-oxadiazole derivatives. The reaction of starting material 4-chloro-m-cresol with ethyl chloroacetate in dry acetone affords ethyl (4-chloro-3-methylphenoxy) acetate, which after reacting with the hydrazine hydrate in ethanol yields 2(4-chloro-3-methylphenoxy) acetohydrazide. When 2(4-chloro-3-methylphenoxy) acetohydrazide was treated with different aromatic aldehydes, aromatic acids and carbon disulfide in alcoholic solution, different 3-acetyl-5-[(4-chloro-3-methylphenoxy) methyl]-2-aryl-2, 3-dihydro-1, 3, 4-oxadiazole and 2-[(4-chloro-3-methylphenoxy) methyl]-5-aryl-1, 3, 4-oxadiazole derivatives were obtained. Purity of the derivatives was confirmed by thin layer chromatography and melting point. Structure of these derivatives was set up by determining infrared spectroscopy, nuclear magnetic resonance spectroscopy and mass spectroscopy. Further, the synthesized derivatives were evaluated for their analgesic and anti-inflammatory activities in rodents. In animal studies, the derivatives 3-acetyl-5-[(4-chloro-3- methylphenoxy)methyl]-2-(4-methoxyphenyl)-2,3-dihydro-1, 3, 4-oxadiazole and 4-{5-[(4-chloro-3- methylphenoxy)methyl]-1, 3, 4-oxadiazol-2-yl}pyridine show more potent analgesic activity and the derivatives 2-{3-acetyl-5-[(4-chloro-3-methylphenoxy)methyl]-2,3-dihydro-1, 3, 4-oxadiazol-2-yl}phenol and 3-acetyl-5- [(4-chloro-3-methylphenoxy)methyl]-2-(4-methoxyphenyl)-2,3-dihydro-1, 3, 4-oxadiazole exhibit more potent anti-inflammatory effect as compared to other derivatives. The results of the current study indicate that cyclization of acetohydrazide produces novel oxadiazole derivatives with potent analgesic and anti-inflammatory activities.

  19. Synthesis and crystal chemistry of two new fluorite-related bismuth phosphates, Bi(4.25)(PO4)2O(3.375) and Bi5(PO4)2O4.5, in the Series Bi4+x(PO4)2O3+3x/2 (0.175 < or = x < or = 1).

    PubMed

    Muktha, B; Guru Row, T N

    2006-06-12

    Two new phosphates, Bi(4.25)(PO4)2O(3.375) and Bi(5)(PO(4))(2)O(4.5), have been analyzed by single-crystal X-ray diffraction in the series Bi(4+x)(PO4)2O(3+3x/2) (0.175 < or = x < or = 1). The syntheses of the compositions ranging from x = 0.175 to 0.475 were carried out by the ceramic route. The compositions from x = 0.175 to 0.475 form a solid solution with a structure similar to that of Bi(4.25)(PO4)2O(3.375), while Bi(5)(PO4)2O(4.5) was isolated from a mixture of two phases. Both of the phases form fluorite-related structures but, nevertheless, differ from each other with respect to the arrangement of the bismuth atoms. The uniqueness in the structures is the appearance of isolated PO(4) tetrahedra separated by interleaving [Bi2O2] units. ac impedance studies indicate conductivity on the order of 10(-5) S cm(-1) for Bi(4.25)(PO4)2O(3.375). Crystal data: Bi(4.25)(PO4)2O(3.375), triclinic, space group P (No. 1), with a = 7.047(1) A, b = 9.863(2) A, c = 15.365(4) A, alpha = 77.604(4) degrees, beta = 84.556(4) degrees, gamma = 70.152(4) degrees, V = 980.90(4) A3, and Z = 4; Bi(5)(PO4)2O(4.5), monoclinic, space group C2/c (No. 15), with a = 13.093(1) A, b = 5.707(1) A, c = 15.293(1) A, beta = 98.240(2) degrees, V = 1130.95(4) A(3), and Z = 8.

  20. 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.

  1. 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.

  2. Biosynthesis of the 1,3,4,6-hexanetetracarboxylic acid subunit of methanofuran

    SciTech Connect

    White, R.H.

    1987-06-02

    /sup 2/H- and /sup 13/C-labeled precursors were used to establish the pathway for the biosynthesis of the 1,3,4,6-hexanetetracarboxylic acid (TCA) component of methanofuran, which is found in some methanogenic bacteria. The extent and position of incorporation of label into TCA were measured from the mass spectrum of the tetramethyl ester of TCA that was prepared from methanofuran present in cells grown in the presence of labeled acetate. (2,2,2-/sup 2/H/sub 3/)Acetate was found to incorporate deuterium into two separate sites of the TCA molecule, with one on each side of the symmetrical molecule. One site was found to be labeled 37% with deuterium, the same as for the glutamic acid present in the cells; the other site was labeled 77% with deuterium, the same as for the malonate-derived compounds in the cells. An analog of TCA, 1-hydroxy-1,3,4,6-hexanetetracarboxylic acid, found in methanofuran isolated from Methanobrevibacter smithii, was found to incorporate /sup 13/C/sub 2/ units from (1,2-/sup 13/C/sub 2/)acetate into three positions of the molecule. One of the acetate /sup 13/C/sub 2/ units was incorporated into the non-hydroxyl-containing side of the molecule (carbons 4, 5, and 6 and the C-6 carboxylic acid group), and two acetate units were incorporated into the hydroxyl-containing side of the molecule (carbons 1, 2, and 3 and the C-1 carboxylic acid group). On the basis of this and additional information, it is concluded that TCA is biosynthesized by the condensation of ..cap alpha..-ketoglutaric acid with malonic acid to form 1,1,2,4-butanetetracarboxylic acid, which is further condensed with a second molecule of malonate, in a series of reactions analogous to those observed during fatty acid biosynthesis, to form TCA.

  3. Characterization and optical properties of novel unsymmetrical stilbene-based 1,3,4-oxadiazole derivatives

    NASA Astrophysics Data System (ADS)

    He, Dao-Hang; Li, Xin-Wei; Yang, Chong; Yang, Jun

    2012-09-01

    A series of novel unsymmetrical stilbene-based 1,3,4-oxadiazole derivatives were efficiently synthesized by a four-pots reaction sequence. All of the title compounds were characterized by MS, 1H-NMR and elemental analysis. UV-Vis absorption and fluorescence emission spectra of the compounds were investigated in dilute chloroform solution; the compounds exhibit strong blue-green fluorescence ranged from 397 to 499 nm and show potential for application in organic optical materials.

  4. Trapping of benzene oxide-oxepin and methyl-substituted derivatives with 4-phenyl- and 4-pentafluorophenyl-1,2,4-triazoline-3,5-dione.

    PubMed

    Henderson, Alistair P; Mutlu, Esra; Leclercq, Amélie; Bleasdale, Christine; Clegg, William; Henderson, Richard A; Golding, Bernard T

    2002-09-07

    4-Phenyl-1,2,4-triazoline-3,5-dione and its pentafluoro analogue are efficient reagents for trapping arene oxides, e.g. benzene oxide-oxepin, affording crystalline adducts that can be quantitatively analysed by HPLC and MS techniques.

  5. 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.

  6. Ethyl 2-(1,2,3,4-tetrahydro­spiro­[carba­zole-3,2′-[1,3]dioxolan]-9-yl)acetate

    PubMed Central

    Löffler, Philipp M. G.; Ulven, Trond; Bond, Andrew D.

    2009-01-01

    In the title compound, C18H21NO4, the hydrogenated six-membered ring of the carbazole unit adopts a half-chair conformation. The dioxolane ring and ethyl­acetate substituent point to opposite sides of the carbazole plane. The ethyl­acetate substituent adopts an essentially fully extended conformation, and its mean plane forms a dihedral angle of 83.8 (1)° with respect to the carbazole mean plane. The mol­ecules are arranged into stacks in which the carbazole planes form a dihedral angle of 4.4 (1)° and have an approximate inter­planar separation of 3.6 Å. PMID:21582427

  7. Lithium Diffusion Pathway in Li(1.3)Al(0.3)Ti(1.7)(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 Li(1+x)Al(x)Ti(2-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.

  8. 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)

  9. 11H-Pyrido[3',2':4,5]pyrrolo[3,2-c]cinnoline and pyrido[3',2':4,5]pyrrolo[1,2-c][1,2,3]benzotriazine: two new ring systems with antitumor activity.

    PubMed

    Parrino, Barbara; Carbone, Anna; Muscarella, Marina; Spanò, Virginia; Montalbano, Alessandra; Barraja, Paola; Salvador, Alessia; Vedaldi, Daniela; Cirrincione, Girolamo; Diana, Patrizia

    2014-11-26

    Derivatives of new ring systems 11H-pyrido[3',2':4,5]pyrrolo[3,2-c]cinnoline and pyrido[3',2':4,5]pyrrolo[1,2-c][1,2,3]benzotriazine have been prepared from the key intermediates 2-(1H-pyrrolo[2,3-b]pyridin-2-yl)anilines in excellent yields (94-99%) and screened by the National Cancer Institute (Bethesda, MD) on about 60 human tumor cell lines derived from nine cancer cell types. The tested compounds exhibited antiproliferative activity against all the human cell lines, showing comparable MG_MID (mean graph midpoint) values in the range of 0.74-1.15 μM. A particular efficacy was observed against the leukemia subpanel (GI50 = 0.73-0.0090 μM). Flow cytometric analysis of the cell cycle demonstrated an increase in the percentage of cells in the G2/M phase. The compounds caused apoptosis of the cells, mitochondrial depolarization, generation of reactive oxygen species, and activation of caspase-3, caspase-8, and caspase-9. Moreover, they acted as topoisomerase I inhibitors.

  10. 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

  11. Synthesis, characterization and anticonvulsant activity evaluation of some 1,4-dihydropyridines and 3,5-(substituted)oxycarbonyl-1,4-dihydro-2,6-dimethyl-N-[2-(4-sulfamoylphenylamino)-acetyl]-4-(substituted)pyridines.

    PubMed

    Subudhi, Bharat Bhusan; Panda, Prasanna K; Swain, Sarada P; Sarangi, Priyambada

    2009-01-01

    A series of 3,5-(substituted)oxycarbonyl-1,4-dihydro-2,6-dimethyl-4-(substituted)pyridines (1a-j) were synthesized by Hantzsch method for pyridine synthesis. Treatment with chloroacetyl chloride produced N-(2-chloroacetyl)-3,5-(substituted)oxycarbonyl-1,4-dihydro-2,6-dimethyl-4-(substituted)pyridines (2a-e), which on further treatment with sulfanilamide resulted in 3,5-(substituted)oxycarbonyl-1,4-dihydro-2,6-dimethyl-N-[2-(4-sulfamoylphenylamino)-acetyl]-4-(substituted)pyridines (3a-e). The structures has been established on the basis of spectral (IR, 1H-NMR, mass) and elemental analysis. Compounds 1a-j and 3a-e (5 mg/kg and 10 mg/kg) were evaluated for their anticonvulsant effect against pentylenetetrazole-induced convulsions with diazepam (4 mg/kg) as the reference. Compounds 3a-e exhibited significant (p<0.01) anticonvulsant activity compared to the control.

  12. Crystal structure of 1-ethyl­pyrazolo[3,4-d]pyrimidine-4(5H)-thione

    PubMed Central

    El Fal, Mohammed; Ramli, Youssef; Essassi, El Mokhtar; Saadi, Mohamed; El Ammari, Lahcen

    2014-01-01

    In the title compound, C7H8N4S, the methyl C atom is displaced by 1.232 (7) Å from the mean plane of the pyrazolo­[3,4-d]pyrimidine ring system (r.m.s. deviation = 0.007 Å). The N—N—C—Cm (m = meth­yl) torsion angle is −60.3 (6)°. In the crystal, mol­ecules are linked by N—H⋯S hydrogen bonds, generating [010] chains, which are reinforced by C—H⋯N inter­actions. The chains are cross-linked by weak C—H⋯S hydrogen bonds, generating (001) sheets. PMID:25309193

  13. 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.

  14. 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.

  15. Synthesis and anticancer activities of novel 1,2,4-triazolo[3,4-a]phthalazine derivatives.

    PubMed

    Xue, Deng-Qi; Zhang, Xu-Yao; Wang, Chao-Jie; Ma, Li-Ying; Zhu, Nan; He, Peng; Shao, Kun-Peng; Chen, Peng-Ju; Gu, Yi-Fei; Zhang, Xiao-Song; Wang, Cai-Feng; Ji, Cong-Hui; Zhang, Qiu-Rong; Liu, Hong-Min

    2014-10-06

    Trying to develop potent and selective anticancer agents, two series of novel 1,2,4-triazolo[3,4-a]phthalazine derivatives were designed and synthesized. Their antitumor activities were evaluated by MTT method against four selected human cancer cell lines (MGC-803, EC-9706, HeLa and MCF-7). Our results showed that compound 11h exhibited good anticancer activities compared to 5-fluorouracil against the four tested cell lines, with IC50 values ranging from 2.0 to 4.5 μM. Flow cytometry analysis indicated that compound 11h induced the cellular early apoptosis and cell cycle arrest at G2/M phase in EC-9706.

  16. The triclinic form of di-μ-aqua-bis-[diaqua-bis-(thio-cyanato-κN)iron(II)]-1,4-bis-(4H-1,2,4-triazol-4-yl)benzene (1/3).

    PubMed

    Yang, Pan; Ding, Bin; Du, Gui-Xiang

    2012-08-01

    In the title compound, [Fe(2)(NCS)(4)(H(2)O)(6)]·3C(10)H(8)N(6), the centrosymmetric dinuclear complex contains two Fe(II) ions bridged by two aqua ligand O atoms, forming a four-membered ring. The slightly distorted octa-hedral coordination environment of the two Fe(II) ions is completed by two monodentate aqua ligands and two thio-cyanate ligands. One of the 1,4-bis-(4H-1,2,4-triazol-4-yl)benzene mol-ecules lies across an inversion center. In the crystal, O-H⋯N hydrogen bonds connect the components, forming a two-dimensional network parallel to (011). In addition, π-π stacking inter-actions involving the benzene and triazole rings, with centroid-centroid distances in the range 3.502 (5)-3.787 (6) Å, connect the two-dimensional hydrogen-bonded network into a three-dimensional network.

  17. Susceptibility of laboratory rats against genotypes 1, 3, 4, and rat hepatitis E viruses.

    PubMed

    Li, Tian-Cheng; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Yasuda, Shumpei P; Yoshimatsu, Kumiko; Arikawa, Jiro; Takeda, Naokazu; Wakita, Takaji

    2013-04-12

    To determine whether or not rats are susceptible to hepatitis E virus (HEV) infection, each of group containing three laboratory rats (Wistar) were experimentally inoculated with genotypes 1, 3, 4 and rat HEV by intravenous injection. Serum and stool samples were collected and used to detect HEV RNA and anti-HEV antibodies by RT-PCR and ELISA, respectively. The virus infection was monitored up to 3 months after inoculation. None of the serum or stool samples collected from the rats inoculated with G1, G3, or G4 HEV indicated positive sign for virus replication. Although no alteration was observed in ALT level, rat HEV RNA was detected in stools from both of the rats inoculated with rat HEV, and both rats were positive for anti-rat HEV IgG and IgM from 3 weeks after inoculation. These results demonstrated that rats are susceptible to rat HEV but not to G1, G3, and G4 HEV. We also confirm that the nude rats were useful for obtaining a large amount of rat HEV and that the rat HEV was transmitted by the fecal-oral route.

  18. Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.

    PubMed

    Tessem, Jeffery S; Moss, Larry G; Chao, Lily C; Arlotto, Michelle; Lu, Danhong; Jensen, Mette V; Stephens, Samuel B; Tontonoz, Peter; Hohmeier, Hans E; Newgard, Christopher B

    2014-04-08

    Loss of functional β-cell mass is a hallmark of type 1 and type 2 diabetes, and methods for restoring these cells are needed. We have previously reported that overexpression of the homeodomain transcription factor NK6 homeobox 1 (Nkx6.1) in rat pancreatic islets induces β-cell proliferation and enhances glucose-stimulated insulin secretion, but the pathway by which Nkx6.1 activates β-cell expansion has not been defined. Here, we demonstrate that Nkx6.1 induces expression of the nuclear receptor subfamily 4, group A, members 1 and 3 (Nr4a1 and Nr4a3) orphan nuclear receptors, and that these factors are both necessary and sufficient for Nkx6.1-mediated β-cell proliferation. Consistent with this finding, global knockout of Nr4a1 results in a decrease in β-cell area in neonatal and young mice. Overexpression of Nkx6.1 and the Nr4a receptors results in increased expression of key cell cycle inducers E2F transcription factor 1 and cyclin E1. Furthermore, Nkx6.1 and Nr4a receptors induce components of the anaphase-promoting complex, including ubiquitin-conjugating enzyme E2C, resulting in degradation of the cell cycle inhibitor p21. These studies identify a unique bipartite pathway for activation of β-cell proliferation, suggesting several unique targets for expansion of functional β-cell mass.

  19. Nano-indentation investigations of (As2Se3)1-x: Snx and (As4S3Se3)1-x: Snx glasses

    NASA Astrophysics Data System (ADS)

    Harea, D. V.; Harea, E. E.; Iaseniuc, O. V.; Iovu, M. S.

    2015-02-01

    Experimental results on some physical and optical properties of (As2Se3)1-x:Snx and (As4S3Se3)1-x:Snx (x = 0-10 at %) glasses and amorphous films (d~2.0 μm) are presented. The bulk chalcogenide glasses are studied by X-ray diffraction spectroscopy and nanoindentation methods. It is established that the addition of these amounts of tin (x = 0-10 at %) does not lead to significant changes in the physical properties of the glass, such as values of stress and Young's modulus related to the modification of the density and compactness. It has been found that the addition of these amounts of tin in (As4S3Se3)1-x:Snx does not lead to significant changes in the glass physical properties, such as values of stress and Young's modulus related to the modification of the density and compactness. The study of the photoplastic effect is performed in situ, with illumination of the bulk and thin film samples during indentation as well as their indentation after illumination with a green laser (λ = 532 nm) at a power of P = 50 mV/cm2. The hardness is calculated from load-displacement curves by the Oliver-Pharr method. A sharp increase in hardness is registered if the tin concentration exceeds a value of 34% Sn. The hardness H of (As2Se3)1-x:Snx films varies between 115 and 130 kg/mm2. It is found that the hardness H of amorphous thin films is generally higher than the hardness of bulk samples with the same chemical composition. In this study, we are focused on the mechanical characteristics of high-purity As2Se3: Snx thin films. Keyword: Chalcogenide glasses, hardness,

  20. Evaluation of 309 molecules as inducers of CYP3A4, CYP2B6, CYP1A2, OATP1B1, OCT1, MDR1, MRP2, MRP3 and BCRP in cryopreserved human hepatocytes in sandwich culture.

    PubMed

    Badolo, Lassina; Jensen, Bente; Säll, Carolina; Norinder, Ulf; Kallunki, Pekka; Montanari, Dino

    2015-02-01

    1. Regulation of hepatic metabolism or transport may lead to increase in drug clearance and compromise efficacy or safety. In this study, cryopreserved human hepatocytes were used to assess the effect of 309 compounds on the activity and mRNA expression (using qPCR techniques) of CYP1A2, CYP2B6 and CYP3A4, as well as mRNA expression of six hepatic transport proteins: OATP1B1 (SCLO1B1), OCT1 (SLC22A1), MDR1 (ABCB1), MRP2 (ABCC2), MRP3 (ABCC3) and BCRP (ABCG2). 2. The results showed that 6% of compounds induced CYP1A2 activity (1.5-fold increase); 30% induced CYP2B6 while 23% induced CYP3A4. qPCR data identified 16, 33 or 32% inducers of CYP1A2, CYP2B6 or CYP3A4, respectively. MRP2 was induced by 27 compounds followed by MDR1 (16)>BCRP (9)>OCT1 (8)>OATP1B1 (5)>MRP3 (2). 3. CYP3A4 appeared to be down-regulated (≥2-fold decrease in mRNA expression) by 53 compounds, 10 for CYP2B6, 6 for OCT1, 4 for BCRP, 2 for CYP1A2 and OATP1B1 and 1 for MDR1 and MRP2. 4. Structure-activity relationship analysis showed that CYP2B6 and CYP3A4 inducers are bulky lipophilic molecules with a higher number of heavy atoms and a lower number of hydrogen bond donors. Finally, a strategy for testing CYP inducers in drug discovery is proposed.