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Sample records for 1 3 4

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

    DOEpatents

    Lee, K.Y.

    1985-03-05

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

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  4. The first 1-alkyl-3-perfluoroalkyl-4,5- dimethyl-1,2,4-triazolium salts.

    PubMed

    Xue, Hong; Twamley, Brendan; Shreeve, Jean'ne M

    2004-02-20

    Syntheses of quaternary 1-alkyl-3-perfluoroalkyl-4,5-dimethyl-1,2,4-triazolium iodides have led to a variety of new quaternary salts via metathesis reactions. 1,4,5-Trimethyl-3-trifluoro-methyl-1,2,4-triazolium iodide (6) with LiN(SO(2)CF(3))(2), KSO(3)CF(3), AgClO(4), AgBF(4); 1-(3-fluoropropyl)-3-trifluoromethyl-4,5-dimethyl-1,2,4-triazolium iodide (7) with LiN(SO(2)CF(3))(2); and 1,4,5-trimethyl-3-perfluorooctyl-1,2,4-triazolium iodide (8) with LiN(SO(2)CF(3))(2), AgClO(4), AgBF(4) gave excellent yields of new thermally stable and relatively low melting quaternary salts. The structure of 1,4,5-trimethyl-3-perfluorooctyl-1,2,4-triazolium tetrafluoroborate (11c) was confirmed by single-crystal X-ray analysis. Although the molecular weight of 11c (cation) is 3-fold greater than that of the 3-trifluoromethyl derivative 9d, its melting point is 32 degrees C lower.

  5. 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).

  6. 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.

  7. (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

  8. Reproduction of 3/4 White Composite and 1/4 Duroc, 1/4 Meishan, 1/4 Fengjing, or 1/4 Minzhu gilts and sows.

    PubMed

    Young, L D

    1998-06-01

    Females were either 1/4 Duroc, 1/4 Meishan, 1/4 Fengjing, or 1/4 Minzhu, and the remainder were 3/4 White Composite. A greater percentage of Fengjing crosses reached puberty than Duroc or Minzhu (P < .05), and Meishan crosses were intermediate and not different (P > .05) from other breed types. After adjusting for differences in percentage detected owing to termination of observation for estrus, breed types ranked Fengjing, Meishan, Minzhu, and Duroc from youngest to oldest at puberty with approximately 14 d between adjacent breed types. Meishan and Fengjing crosses had a greater (P < .05) ovulation rate than Minzhu or Duroc crosses. With the exception of number of fetuses at 100 d and average fetal weight at 60 d, differences among breed types were not detected (P > .05) for litter or uterine traits measured on gilts slaughtered at 60 or 100 d of gestation. Total number of pigs born was greater (P < .05) for 1/4 Fengjing than for 1/4 Duroc gilts. Gestation length, number born alive, number weaned, litter birth weight, or litter weaning weight for gilts did not differ (P > .05) among breed types. Duroc crosses were heavier (P < .01) than Chinese crosses at d 1 and 28 after farrowing, but breed types did not differ (P > .05) for backfat thickness at those times. Breed types did not differ (P > .05) for the ratio of litter gain from 0 to 28 d/total Mcal or any of the component traits in the ratio. Postweaning estrus activity, conception rate, and litter and uterine traits of sows bred for second parity were not affected (P > .05) by breed type. These analyses indicate that crossbred gilts containing 1/4 Meishan, 1/4 Fengjing, or 1/4 Minzhu will reach puberty earlier, have larger litters, and weigh less at first parity than gilts containing 1/4 Duroc, but they do not have any significant advantage in litter size at second parity.

  9. 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...

  10. 4-(4-bromophenyl)-2-methyl-1,3-thiazole.

    PubMed

    Rodríguez de Barbarín, Cecilia; Bernès, Sylvain; Sánchez-Viesca, Francisco; Berros, Martha

    2003-07-01

    In the structure of the title compound, C(10)H(8)BrNS, the dihedral angles between the planes of the thiazole and aryl rings, viz. 4.2 (6) and 7.5 (6) degrees for the two independent molecules, are consistent with insignificant molecular perturbation by the weak intermolecular contacts. The molecules are close to being related by a non-crystallographic inversion centre, with C-H.pi and pi-pi intermolecular interactions observed.

  11. 1,2,3,3',4',6'-Hexaacetyl-4,6-O-benzyl-idenesucrose.

    PubMed

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

    2011-01-01

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

  12. 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.

  13. 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.

  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, 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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.

  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. 3-Benzyl-2-(4-fluorophenyl)-1,3-thiazolidin-4-one.

    PubMed

    Gutiérrez, Alexander; Insuasty, Braulio; Cobo, Justo; Glidewell, Christopher

    2011-01-01

    The title compound, C(16)H(14)FNOS, crystallizes with Z' = 2 in the space group P2(1)/c. In one of the two independent molecules, the heterocyclic ring is effectively planar, but in the other molecule this ring adopts an envelope conformation. The molecules are weakly linked by two C-H···O hydrogen bonds to form C(2)(2)(14) chains. Comparisons are made with some symmetrically substituted 2-aryl-3-benzyl-1,3-thiazolidin-4-ones.

  2. 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

  3. 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).

  4. 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.

  5. Reaction of dichlorocarbene with 4-phenyl-1,3-dioxane

    SciTech Connect

    Safiev, O.G.; Nazarov, D.V.; Zorin, V.V.; Rakhmankulov, D.L.

    1988-02-20

    The authors have established for the first time that the reaction of 4-phenyl-1,3-dioxane with the dichlorocarbene generated from chloroform by the action of a 50% aqueous solution of sodium hydroxide in the presence of triethylbenzylammonium chloride as phase-transfer catalysis leads to the formation of 4-phenyl-4-dichloromethyl-1,3-dioxane with a yield of 70% on the transformed reagent with 35% conversion with respect to the substrate. The product was isolated by column liquid chromatography. It was identified by means of the PMR and /sup 13/C NMR spectra and by the data from elemental analysis.

  6. 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.

  7. 10 CFR 960.3-1-4-1 - Site identification as potentially acceptable.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  8. 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...

  9. 40 CFR 721.1920 - 1,4-Bis(3-hydroxy-4-benzoylphenoxy)butane.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 1,4-Bis(3-hydroxy-4-benzoylphenoxy)butane. 721.1920 Section 721.1920 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.1920 1,4-Bis(3-hydroxy-4-benzoylphenoxy)butane. (a) Chemical...

  10. 40 CFR 721.1920 - 1,4-Bis(3-hydroxy-4-benzoylphenoxy)butane.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1,4-Bis(3-hydroxy-4-benzoylphenoxy)butane. 721.1920 Section 721.1920 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.1920 1,4-Bis(3-hydroxy-4-benzoylphenoxy)butane. (a) Chemical...

  11. 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…

  12. 3,4,6-Trimethyl-1-phenyl-1H-pyrazolo­[3,4-b]pyridine

    PubMed Central

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

    2010-01-01

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

  13. Bis­(3,5-diamino-4H-1,2,4-triazol-1-ium) 3,4-dioxocyclo­butane-1,2-diolate

    PubMed Central

    Fun, Hoong-Kun; Loh, Wan-Sin; Johnson, Atim; Yousuf, Sammer; Eno, Ededet

    2013-01-01

    The asymmetric unit of the title compound, 2C2H6N5 +·C4O4 2−, contains two 3,5-diamino-4H-1,2,4-triazolium cations and one squarate dianion. The squaric acid mol­ecule donated one H atom to each of the two 3,5-diamino-1,2,4-triazole mol­ecules at their N atoms. The squaric acid dianion has four C—O bonds which are shorter than a normal single C—O bond (1.426 Å) and are slightly longer than a normal C=O bond (1.23 Å), which indicates the degree of electron delocalization in the dianion. In the crystal, the cations and dianions are linked by N—H⋯N and N—H⋯O hydrogen bonds into a three-dimensional network. PMID:23476545

  14. Fragrance material review on 1-(3,3-dimethylcyclohexyl)pent-4-en-1-one.

    PubMed

    Scognamiglio, J; Letizia, C S; Api, A M

    2013-12-01

    A toxicologic and dermatologic review of 1-(3,3-dimethylcyclohexyl)pent-4-en-1-one when used as a fragrance ingredient is presented. 1-(3,3-Dimethylcyclohexyl)pent-4-en-1-one is a member of the fragrance structural group Alkyl Cyclic Ketones. These fragrances can be described as being composed of an alkyl, R1, and various substituted and bicyclic saturated or unsaturated cyclic hydrocarbons, R2, in which one of the rings may include up to 12 carbons. Alternatively, R2 may be a carbon bridge of C2-C4 carbon chain length between the ketone and cyclic hydrocarbon. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 1-(3,3-dimethylcyclohexyl)pent-4-en-1-one were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, repeated dose, and genotoxicity data. A safety assessment of the entire Alkyl Cyclic Ketones will be published simultaneously with this document; please refer to Belsito et al. (Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2013. A toxicologic and dermatologic assessment of alkyl cyclic ketones when used as fragrance ingredients (submitted for publication) for an overall assessment of the safe use of this material and all Alkyl Cyclic Ketones in fragrances.

  15. 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.

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

    PubMed

    Megally Abdo, Nadia Youssef; Kamel, Mona Monir

    2015-01-01

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

  17. 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...

  18. 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...

  19. 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

  20. 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.

  1. 40 CFR 721.9662 - Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro- (9CI).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Thieno -1,4-dioxin, 2,3-dihydro- (9CI... Substances § 721.9662 Thieno -1,4-dioxin, 2,3-dihydro- (9CI). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as thieno -1,4-dioxin, 2,3-dihydro- (9CI)...

  2. 40 CFR 721.9662 - Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro- (9CI).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Thieno -1,4-dioxin, 2,3-dihydro- (9CI... Substances § 721.9662 Thieno -1,4-dioxin, 2,3-dihydro- (9CI). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as thieno -1,4-dioxin, 2,3-dihydro- (9CI)...

  3. 40 CFR 721.9662 - Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro- (9CI).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Thieno -1,4-dioxin, 2,3-dihydro- (9CI... Substances § 721.9662 Thieno -1,4-dioxin, 2,3-dihydro- (9CI). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as thieno -1,4-dioxin, 2,3-dihydro- (9CI)...

  4. 40 CFR 721.9662 - Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro- (9CI).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Thieno -1,4-dioxin, 2,3-dihydro- (9CI... Substances § 721.9662 Thieno -1,4-dioxin, 2,3-dihydro- (9CI). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as thieno -1,4-dioxin, 2,3-dihydro- (9CI)...

  5. 40 CFR 721.9662 - Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro- (9CI).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Thieno -1,4-dioxin, 2,3-dihydro- (9CI... Substances § 721.9662 Thieno -1,4-dioxin, 2,3-dihydro- (9CI). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as thieno -1,4-dioxin, 2,3-dihydro- (9CI)...

  6. 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.

  7. 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.

  8. 3-Benzyl-4-ethyl-1H-1,2,4-triazole-5(4H)-thione

    PubMed Central

    Karczmarzyk, Zbigniew; Pitucha, Monika; Wysocki, Waldemar; Pachuta-Stec, Anna; Stańczuk, Andrzej

    2013-01-01

    The title compound, C11H13N3S, exists in the 5-thioxo tautomeric form. The benzene ring exhibits disorder with a refined ratio of 0.77 (2):0.23 (2) for components A and B with a common bridgehead C atom. The 1,2,4-triazole ring is essentially planar, with a maximum deviation of 0.002 (3) Å for the benzyl-substituted C atom, and forms dihedral angles of 88.94 (18) and 86.56 (49)° with the benzene rings of components A and B, respectively. The angle between the plane of the ethyl chain and the mean plane of 1,2,4-triazole ring is 88.55 (15)° and this conformation is stabilized by an intra­molecular C—H⋯S contact. In the crystal, pairs of N—H⋯S hydrogen bonds link mol­ecules into inversion dimers. π–π inter­actions are observed between the triazole and benzene rings, with centroid–centroid separations of 3.547 (4) and 3.544 (12) Å for components A and B, and slippages of 0.49 (6) and 0.58 (15) Å, respectively. PMID:23424446

  9. Interactions between 3,4-methylenedioxymethamphetamine and σ1 Receptors

    PubMed Central

    Brammer, Matthew K.; Gilmore, Deborah L.; Matsumoto, Rae R.

    2006-01-01

    Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) are structurally similar and represent a serious and growing health threat. Earlier studies in our laboratory have shown that methamphetamine interacts with σ receptors and that antagonism of these receptors can attenuate methamphetamine-induced locomotor stimulation and neurotoxicity. However, no research exists which characterizes the interaction between σ receptors and MDMA. Therefore, the goal of the present study was to determine whether σ receptors are involved in the actions of MDMA. In the first part of the study, competition and saturation binding assays were performed to measure the interaction of MDMA with σ receptors. The receptor binding assays revealed that MDMA interacts preferentially with the σ1 subtype, as compared to the σ2 subtype, and that this interaction occurs in a competitive manner. The second part of the study focused on behavioral measurements in male, Swiss Webster mice to determine whether a selective σ1 receptor antagonist, BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine, 0-30 mg/kg, i.p.) could attenuate the locomotor stimulant actions of MDMA (0-50 mg/kg, i.p.). BD1063 alone had no effect on locomotor activity, but dose-dependently attenuated the locomotor stimulant effects of (+)-MDMA and produced a significant shift to the right in the MDMA dose response curve. Together, the data support the functional relevance of the interaction of MDMA with σ1 receptors, and suggest that these receptors are involved in the stimulant actions of MDMA. PMID:17070798

  10. 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

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

    PubMed

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

    2004-05-01

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

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

    PubMed

    Zeng, Wu-Lan

    2011-06-01

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

  13. Acute hepatotoxicity of the polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphtaline (AHTN).

    PubMed

    Steinberg, P; Fischer, T; Arand, M; Park, E; Elmadfa, I; Rimkus, G; Brunn, H; Dienes, H P

    1999-12-20

    Synthetic musks are present in fine fragrances, cosmetics, soaps and laundry detergents. One of the most important synthetic musks is 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydro-naphthaline+ ++ (AHTN; annual production: about 1500 metric tons). An increasing number of studies show that AHTN accumulates in surface water and fish and can be detected in human adipose tissue, as well in human milk. In the present report it is shown that a single high dose of AHTN leads to acute hepatic damage in rats, characterized by single cell necrosis, inflammation, swelling of liver parenchymal cells, and the presence of cytoplasmic condensations in the hepatocytes, while at the ultrastructural level disorganization of the rough endoplasmic reticulum and mitochondria as well as focal cytolysis is evident. Furthermore, evidence is presented that AHTN is not genotoxic, does not induce peroxisome proliferation, and does not lead to the induction of drug-metabolizing enzymes as phenobarbital and 3-methylcholanthrene do.

  14. 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…

  15. Synthesis and biological evaluation of 3-biphenyl-4-yl-4-phenyl-4H-1,2,4-triazoles as novel glycine transporter 1 inhibitors.

    PubMed

    Sugane, Takashi; Tobe, Takahiko; Hamaguchi, Wataru; Shimada, Itsuro; Maeno, Kyoichi; Miyata, Junji; Suzuki, Takeshi; Kimizuka, Tetsuya; Kohara, Atsuyuki; Morita, Takuma; Doihara, Hitoshi; Saita, Kyouko; Aota, Masaki; Furutani, Masako; Shimada, Yoshiaki; Hamada, Noritaka; Sakamoto, Shuichi; Tsukamoto, Shin-ichi

    2011-01-13

    We describe the preparation and evaluation of a novel series of glycine transporter 1 (GlyT1) inhibitors derived from a high-throughput screening hit. The SAR studies resulted in the discovery of 3-biphenyl-4-yl-4-(2-fluorophenyl)-5-isopropyl-4H-1,2,4-triazole (6p). A pharmacokinetic study was also conducted and revealed that 6p had excellent oral bioavailability and ameliorated learning impairment in passive avoidance tasks in mice.

  16. 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.

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

    PubMed Central

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

    2014-01-01

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

  18. 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.

  19. 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.

  20. 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.

  1. Optical resolution by preferential crystallization of (1RS,3RS)-1,2,3,4-tetrahydro-6,7-dihydroxy-1-methyl-3-isoquinolinecarboxylic acid.

    PubMed

    Shiraiwa, Tadashi; Kiyoe, Ryuuichi

    2005-09-01

    The racemic structure of (1RS,3RS)-1,2,3,4-tetrahydro-6,7-dihydroxy-1-methyl-3-isoquinolinecarboxylic acid [(1RS,3RS)-1] was examined based on the melting point, solubility, and IR spectrum, with the aim of optical resolution by preferential crystallization. (1RS,3RS)-1 was indicated from these results to exist as a conglomerate. The successive optical resolution by preferential crystallization of (1RS,3RS)-1 yielded (1S,3S)- and (1R,3R)-1 with optical purities of 85--95% at 66--81% degrees of resolution, which were fully purified by recrystallization.

  2. A Qualitative Comparison of the Reactivities of 3,4,4,5-Tetrachloro-4H-1,2,6-thiadiazine and 4,5-Dichloro-1,2,3-dithiazolium Chloride.

    PubMed

    Kalogirou, Andreas S; Koutentis, Panayiotis A

    2015-01-01

    The high yielding transformations of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine into 3,5-dichloro-4H-1,2,6-thiadiazin-4-one (up to 85%) and 2-(3,5-dichloro-4H-1,2,6-thiadiazin-4-ylidene)malononitrile (up to 83%) have been investigated and compared to the analogous transformations of the closely-related 4,5-dichloro-1,2,3-dithiazolium chloride (Appel's salt) into 4-chloro-5H-1,2,3-dithiazol-5-one and 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)malononitrile. Furthermore, cyclocondensation of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine with 2-aminophenol and 1,2-benzenediamines gave fused 4H-1,2,6-thiadiazines in 68%-85% yields. PMID:26274946

  3. (Z)-2-(3-hydroxy-4-methoxybenzylidene)-1-azabicyclo[2.2.2]octan-3-one.

    PubMed

    Sonar, Vijayakumar N; Parkin, Sean; Crooks, Peter A

    2003-11-01

    Crystals of the title compound, C(15)H(17)NO(3), were obtained from a condensation reaction of 3-hydroxy-4-methoxybenzaldehyde with 1-azabicyclo[2.2.2]octan-3-one and subsequent crystallization of the product from methanol. The title compound, containing a double bond that connects the azabicyclic ring system to the 3-hydroxy-4-methoxybenzylidene group, was obtained with Z geometry.

  4. 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.

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

    PubMed

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

    2016-10-01

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

  6. Synthesis and diversification of 1,2,3-triazole-fused 1,4-benzodiazepine scaffolds.

    PubMed

    Donald, James R; Martin, Stephen F

    2011-03-01

    A substituted heterocyclic scaffold comprising a 1,4-benzodiazepine fused with a 1,2,3-triazole ring has been synthesized and diversified via a variety of refunctionalizations. The strategy features the rapid assembly of the scaffold by combining 3-4 reactants in an efficient multicomponent assembly process, followed by an intramolecular Huisgen cycloaddition.

  7. 40 CFR 721.10379 - Propanoic acid, 3-(dodecylthio)-, 2-(1,1-dimethylethyl)-4-[[5-(1,1-dimethylethyl)-4-hydroxy-2...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  8. 40 CFR 721.10379 - Propanoic acid, 3-(dodecylthio)-, 2-(1,1-dimethylethyl)-4-[[5-(1,1-dimethylethyl)-4-hydroxy-2...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

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

    PubMed

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

    2016-05-01

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

  11. 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. PMID:26228905

  12. 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.

  13. 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

  14. Heterologous production of two unusual acyclic carotenoids, 1,1'-dihydroxy-3,4-didehydrolycopene and 1-hydroxy-3,4,3',4'-tetradehydrolycopene by combination of the crtC and crtD genes from Rhodobacter and Rubrivivax.

    PubMed

    Steiger, Sabine; Takaichi, Shinichi; Sandmann, Gerhard

    2002-07-17

    Acyclic hydroxy carotenoids were produced from lycopene and 3,4-didehydrolycopene in Escherichia coli by combining different carotenogenic genes including the carotene hydratase gene crtC and the carotene 3,4-desaturase gene crtD. The genes originated either from Rhodobacter species or Rubrivivax gelatinosus. It was shown that the product of crtD from Rubrivivax unlike the one from Rhodobacter is able to convert 1-HO-3,4-didehydrolycopene to 1-HO-3,4,3',4'-tetradehydrolycopene (=3,4,3',4'-tetradehydro-1,2-dihydro-psi,psi-caroten-1-ol). Thus, only when the desaturase from Rubrivivax is expressed can this novel carotenoid be obtained. In the presence of crtC from Rubrivivax, another carotenoid 1,1'-(HO)(2)-3,4-didehydrolycopene (=3,4-didehydrolycopene-1,2,1',2'-tetrahydro-psi,psi-caroten-1,1'-diol) not found in a non-transgenic organism before is formed in E. coli. Its accumulation under these conditions and its absence when crtC from Rubrivivax is replaced by the corresponding gene from Rhodobacter is discussed. The function of the different crtC and crtD genes in the pathway leading to the individual carotenoids is outlined. Since 1,1'-(HO)(2)-3,4-didehydrolycopene could not be produced in substantial amounts and 1-HO-3,4,3',4'-tetradehydrolycopene has not been described before, their structural characteristics were determined for the definite assignment of their identity. This included spectral properties, determination of relative molecular mass as well as the number of hydroxy groups by mass spectroscopy and NMR spectroscopy for 1,1'-(HO)(2)-3,4-didehydrolycopene.

  15. 10 CFR 960.3-1-4-1 - Site identification as potentially acceptable.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... will consider the aquatic and terrestrial ecology; water rights and uses; topography; potential offsite... POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-1 Site...

  16. 10 CFR 960.3-1-4-1 - Site identification as potentially acceptable.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... will consider the aquatic and terrestrial ecology; water rights and uses; topography; potential offsite... POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-1 Site...

  17. 10 CFR 960.3-1-4-1 - Site identification as potentially acceptable.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... will consider the aquatic and terrestrial ecology; water rights and uses; topography; potential offsite... POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-1 Site...

  18. Synthesis of N-Aryl-3,5-dichloro-4H-1,2,6-thiadiazin-4-imines from 3,4,4,5-Tetrachloro-4H-1,2,6-thiadiazine.

    PubMed

    Kalogirou, Andreas S; Manoli, Maria; Koutentis, Panayiotis A

    2015-08-21

    Condensation of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine with a range of anilines gave 22 N-aryl-3,5-dichloro-4H-1,2,6-thiadiazin-4-imines in 43-96% yields. The scope and limitations of this condensation are briefly investigated. Furthermore, mono- and bis-substitution of the C-3 and C-5 chlorines of 3,5-dichloro-N-phenyl-4H-1,2,6-thiadiazin-4-imine by amine and alkoxide nucleophiles is explored. Finally, Stille coupling chemistry is used to prepare several N-phenyl-3,5-diaryl-4H-1,2,6-thiadiazin-4-imines. PMID:26261875

  19. Rubidium 2,4,6-trioxo-1,3-diazinan-5-ide-1,3-diazinane-2,4,6-trione-water (1/1/1).

    PubMed

    Gryl, Marlena; Stadnicka, Katarzyna

    2011-05-01

    The asymmetric unit of the title compound, Rb(+)·C(4)H(3)N(2)O(3) (-)·C(4)H(4)N(2)O(3)·H(2)O, consists of one rubidium cation, a barbituric acid mol-ecule, a barbiturate anion and one water mol-ecule. The rubidium ion has seven close-contact inter-actions with O atoms, with Rb⋯O distances ranging from 2.8594 (16) to 3.2641 (14) Å. These seven O atoms together with an eighth O atom at 3.492 (2) Å away from Rb form a distorted polyhedron with shape inter-mediate between an anti-prism and a dodeca-hedron. The Rb(+) ions connect layers built of organic components and water mol-ecules linked via N-H⋯O and O-H⋯O hydrogen bonds. PMID:21754300

  20. Preparation of 1,4-oxaselenin from agNO(3)/LDA-assisted reaction of 3-selena-4-pentyn-1-one as potential antitumor agents.

    PubMed

    Koketsu, M; Yang, H O; Kim, Y M; Ichihashi, M; Ishihara, H

    2001-05-31

    1,4-Oxaselenins were synthesized from 3-selena-4-pentyn-1-ones by the use of AgNO(3) and LDA. One of the obtained oxaselenins, 2-(4-chlorophenyl)-6-phenyl-1,4-oxaselenin 5c, showed an inhibitory effect against the proliferation of human cancer cells and inducing effects on the early stage of apoptosis.

  1. 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.

  2. 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.

  3. Synthetic, Infrared, 1H and 13C NMR Spectral Studies on N-(2/3/4-Substituted Phenyl)-2,4-Disubstituted Benzenesulphonamides, 2,4-(CH3)2/2-CH3-4-Cl/2,4-Cl2C6H3SO2NH(i-XC6H4) (i-X = H, 2-CH3, 3-CH3, 4-CH3, 2-Cl, 3-Cl, 4-Cl, 4-F, 4-Br)

    NASA Astrophysics Data System (ADS)

    Basappa, Savitha M.; Gowda, Basavalinganadoddy Thimme

    2006-11-01

    Twenty six N-(2/3/4-substituted phenyl)-2,4-disubstituted benzenesulphonamides of the general formulae 2,4-(CH3)2C6H3SO2NH(i-XC6H4), 2-CH3-4-ClC6H3SO2NH(i-XC6H4) and 2,4- Cl2C6H3SO2NH(i-XC6H4), where i-X = H, 2-CH3, 3-CH3, 4-CH3, 2-Cl, 3-Cl, 4-Cl, 4-F or 4-Br, have been prepared, characterized and their infrared spectra in the solid state and 1H and 13C NMR spectra in solution studied. The infrared N-H stretching vibrational frequencies vary in the range 3298 - 3233 cm-1. Asymmetric and symmetric SO stretching vibrations appear in the ranges 1373 - 1311 cm-1 and 1177 - 1140 cm-1, respectively, while C-S, S-N and C-N stretching absorptions vary in the ranges 840 - 812 cm-1, 972 - 908 cm-1 and 1295 - 1209 cm-1, respectively. The various 1H and 13C NMR chemical shifts are assigned to the protons and carbon atoms of the two benzene rings in line with those for similar compounds. The incremental shifts due to the groups in the parent compounds have been computed by comparing the chemical shifts of the protons or carbon atoms in these compounds with those of benzene or aniline, respectively. The computed incremental shifts and other data were used to calculate the 1H and 13C NMR chemical shifts of the substituted compounds in three different ways. The calculated chemical shifts by the three methods compared well with each other and with the observed chemical shifts. It is observed that there are no particular trends in the variation of either the infrared absorption frequencies or the chemical shifts with the nature or site of substitution.

  4. [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

  5. 40 CFR 721.8940 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  7. 40 CFR 721.8950 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  8. 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

  9. Absolute configuration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol formed metabolically from 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

    PubMed

    Hecht, S S; Spratt, T E; Trushin, N

    1997-09-01

    4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is an important metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Using the chiral derivatizing agent, (R)-(+)-alpha-methylbenzyl isocyanate [(R)-(+)-MBIC], previous work has shown that the enantiomeric ratio of metabolically formed NNAL and its glucuronide derivative may be species dependent. However, the absolute configuration of such NNAL has not been previously reported. Synthetically prepared racemic NNAL was converted to diastereomeric esters by reaction with (R)-(+)- and (S)-(-)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetic acid (MTPA) chloride (Mosher's reagent) and the products were characterized by 1H-NMR. Based on chemical shift data, the absolute configuration of NNAL in each diastereomeric ester was assigned. Hydrolysis of (R)-NNAL-(R)-MTPA gave (R)-NNAL. This was converted to the corresponding carbamate by reaction with (R)-(+)-alpha-MBIC and the absolute configurations of the diastereomeric carbamates formed by reaction of (R)- and (S)-NNAL with (R)-(+)-MBIC were thereby assigned. Conversion of metabolically produced NNAL to the same carbamates allowed us to assign the NNAL formed from NNK by rat liver microsomes as (R)-NNAL. The major and minor NNAL-glucuronide diastereomers found in the urine of patas monkeys and humans exposed to NNK were similarly assigned; they were formed from (R)-NNAL and (S)-NNAL, respectively.

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

    NASA Astrophysics Data System (ADS)

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

    2011-01-01

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

  11. 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.

  12. 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...

  13. 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.

  14. 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.

  15. 4-(5-Phenyl-1,2,4-triazolo[3,4-a]isoquinolin-3-yl)benzonitrile

    PubMed Central

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

    2010-01-01

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

  16. 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.

  17. 4,4'-Dichlorodiphenyltrichloroethane (DDT) and 4,4'-dichlorodiphenyldichloroethylene (DDE) promote adipogenesis in 3T3-L1 adipocyte cell culture.

    PubMed

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

    2016-07-01

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

  18. 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.

  19. 4-Oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as New Axl Kinase Inhibitors.

    PubMed

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

    2016-07-28

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

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

    PubMed

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

    2015-10-15

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

  1. 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.

  2. 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.

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

    PubMed

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

    2016-04-22

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

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

    SciTech Connect

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

    1986-05-01

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

  5. 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

  6. The D4 Flavor Symmetry in 3-3-1 Model with Neutral Leptons

    NASA Astrophysics Data System (ADS)

    Vien, V. V.; Long, H. N.

    2013-12-01

    We construct a D4 flavor model based on SU(3)C ⊗SU(3)L ⊗U(1)X gauge symmetry responsible for fermion masses and mixings. The neutrinos get small masses from antisextets which are in a singlet and a doublet under D4. If the D4 symmetry is violated as perturbation by a Higgs triplet under SU(3)L and lying in \\underline{1}''' of D4, the corresponding neutrino mass mixing matrix gets the most general form. In this case, the model can fit the experimental data in 2012 on neutrino masses and mixing. Our results show that the neutrino masses are naturally small and a little deviation from the tribimaximal neutrino mixing form can be realized. The quark masses and mixing matrix are also discussed. In the model under consideration, the CKM matrix can be different from the unit matrix. The scalar potential of the model is more simpler than those of the model based on S3 and S4. Assignation of VEVs to antisextets leads to the mixing of the new gauge bosons and those in the Standard Model. The mixing in the charged gauge bosons as well as the neutral gauge boson is considered.

  7. Characterization of VAMP isoforms in 3T3-L1 adipocytes: implications for GLUT4 trafficking.

    PubMed

    Sadler, Jessica B A; Bryant, Nia J; Gould, Gwyn W

    2015-02-01

    The fusion of GLUT4-containing vesicles with the plasma membrane of adipocytes is a key facet of insulin action. This process is mediated by the formation of functional soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes between the plasma membrane t-SNARE complex and the vesicle v-SNARE or VAMP. The t-SNARE complex consists of Syntaxin4 and SNAP23, and whereas many studies identify VAMP2 as the v-SNARE, others suggest that either VAMP3 or VAMP8 may also fulfil this role. Here we characterized the levels of expression, distribution, and association of all the VAMPs expressed in 3T3-L1 adipocytes to provide the first systematic analysis of all members of this protein family for any cell type. Despite our finding that all VAMP isoforms form SDS-resistant SNARE complexes with Syntaxin4/SNAP23 in vitro, a combination of levels of expression (which vary by >30-fold), subcellular distribution, and coimmunoprecipitation analyses lead us to propose that VAMP2 is the major v-SNARE involved in GLUT4 trafficking to the surface of 3T3-L1 adipocytes.

  8. Characterization of VAMP isoforms in 3T3-L1 adipocytes: implications for GLUT4 trafficking

    PubMed Central

    Sadler, Jessica B. A.; Bryant, Nia J.; Gould, Gwyn W.

    2015-01-01

    The fusion of GLUT4-containing vesicles with the plasma membrane of adipocytes is a key facet of insulin action. This process is mediated by the formation of functional soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) complexes between the plasma membrane t-SNARE complex and the vesicle v-SNARE or VAMP. The t-SNARE complex consists of Syntaxin4 and SNAP23, and whereas many studies identify VAMP2 as the v-SNARE, others suggest that either VAMP3 or VAMP8 may also fulfil this role. Here we characterized the levels of expression, distribution, and association of all the VAMPs expressed in 3T3-L1 adipocytes to provide the first systematic analysis of all members of this protein family for any cell type. Despite our finding that all VAMP isoforms form SDS-resistant SNARE complexes with Syntaxin4/SNAP23 in vitro, a combination of levels of expression (which vary by >30-fold), subcellular distribution, and coimmunoprecipitation analyses lead us to propose that VAMP2 is the major v-SNARE involved in GLUT4 trafficking to the surface of 3T3-L1 adipocytes. PMID:25501368

  9. 10 CFR 960.3-1-4-2 - Site nomination for characterization.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Site nomination for characterization. 960.3-1-4-2 Section 960.3-1-4-2 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-2 Site nomination...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

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

    PubMed

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

    2015-12-01

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

  16. 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

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

    PubMed

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

    2013-06-01

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

  18. 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

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

    PubMed

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

    2011-10-01

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

  20. 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...

  1. Facile synthesis and herbicidal evaluation of 4H-3,1-benzoxazin-4-ones and 3H-quinazolin-4-ones with 2-phenoxymethyl substituents.

    PubMed

    Aibibuli, Zumuretiguli; Wang, Yufeng; Tu, Haiyang; Huang, Xiaoting; Zhang, Aidong

    2012-03-14

    Series of 4H-3,1-benzoxazin-4-ones and 3H-quinazolin-4-ones with phenoxy-methyl substituents were rationally designed and easily synthesized via one-pot N-acylation/ring closure reactions of anthranilic acids with 2-phenoxyacetyl chlorides to yield the 4H-3,1-benzoxazin-4-ones, and subsequently substituted with amino derivatives to obtain the 3H-quinazolin-4-ones. The herbicidal evaluation was performed on the model plants barnyard grass (a monocotyledon) and rape (a dicotyledon), and most of the title compounds displayed high levels of phytotoxicity. The active substructure and inhibitory phenotype analysis indicated that these compounds could be attributed to the class of plant hormone inhibitors. A docking study of several representative compounds with the hormone receptor TIR1 revealed an appreciable conformational match in the active site, implicating these compounds are potential lead hits targeting this receptor.

  2. Synthesis and antifungal activities of 2-(N-arylsulfonylindol-3-yl)-3-aryl-1,3-thiazinan-4-ones.

    PubMed

    Qu, Huan; Zhang, Rui; Hu, Ying; Ke, Yazhen; Gao, Zhinan; Xu, Hui

    2013-01-01

    A series of 2-(N-arylsulfonylindol-3-yl)-3-aryl-1,3-thiazinan-4-one derivatives were synthesized and evaluated in vitro against seven phytopathogenic fungi, namely Fusarium graminearum, Alternaria solani, Fusarium oxysporium f. sp. vasinfectum, Alternaria brassicae, Valsa mali, Alternaria alternata, and Pyricularia oryzae. Among all derivatives, especially compound 4j exhibited a potential antifungal activity against four phytopathogenic fungi. PMID:23819301

  3. 1,3,4,6,7,9-Hexamethylbenzo[1,2-c:3,4-c':5,6-c'']trithiophene: a twisted heteroarene.

    PubMed

    Wu, Yao-Ting; Tai, Chia-Cheng; Lin, Wei-Chih; Baldridge, Kim K

    2009-07-01

    1,3,4,6,7,9-Hexamethylbenzo[1,2-c:3,4-c':5,6-c'']trithiophene (C-Me) was prepared by palladium-catalyzed methylations of the corresponding hexabromide C-Br. The twisted structure of C-Me has been confirmed by X-ray crystal analysis. The physical properties of twisted C-Me and planar benzo[1,2-c:3,4-c':5,6-c'']trithiophene (C-H) were studied and compared. Crystal structures are compared to computational structures determined using density functional theory, with both the M06-2X and B3PW91 functionals.

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

    NASA Technical Reports Server (NTRS)

    Wielicki, Bruce A. (Principal Investigator)

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

  5. 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.

  6. 1-(1H-Indol-3-ylcarbonyl)-N-(4-methoxybenzyl)formamide.

    PubMed

    Sonar, Vijayakumar N; Parkin, Sean; Crooks, Peter A

    2006-03-01

    In the title compound, C18H16N2O3, the indole ring is planar and the two adjacent carbonyl groups are mutually trans oriented with a torsion angle of 144.8 (3) degrees. The single C-C bond linking the two carbonyl functionalities is 1.539 (4) A. Molecules are linked into a two-dimensional network by intermolecular N-H...O hydrogen bonds.

  7. 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.

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

    PubMed

    Staun, Selena L; Oliver, Allen G

    2015-11-01

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

  9. 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%). PMID:26963527

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

    PubMed Central

    Farahat, Abdelbasset A.; Boykin, David W.

    2014-01-01

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

  11. 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.

  12. 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.

  13. 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.

  14. The nuclear orphan receptor NR4A1 and NR4A3 as tumor suppressors in hematologic neoplasms.

    PubMed

    Wenzl, Kerstin; Troppan, Katharina; Neumeister, Peter; Deutsch, Alexander J A

    2015-01-01

    NR4A1 (Nur77) belongs together with NR4A2 (Nurr1) and NR4A3 (NOR-1) to the nuclear orphan receptors of the NR4A-family. Their activation is generally short lived, the cellular outcome is a stimulus- and cell context-dependent differential activation of NR4A target genes that regulate cell cycle, apoptosis, inflammation, atherogenesis, metabolism, DNA repair and tumorigenesis. NR4A1 and NR4A3 were identified to function as tumor suppressors in acute myeloid leukemia (AML). Deletion of both nuclear receptors led to rapid development of AML in mice. Loss of NR4A1 and NR4A3 was a common feature in human AML patients. Additionally, NR4A1 and NR4A3 hypoallelic mice - mice with a reduced NR4A1 and NR4A3 expression - develop a chronic myeloid malignancy that recapitulates the pathological features of myelodysplastic/ myeloproliferative neoplasms with progression to AML in rare cases. Recently, a reduced NR4A1 and NR4A3 expression was described in aggressive lymphomas and low NR4A1 expression was associated with poor overall survival. Overexpression of NR4A1 in aggressive lymphoma cells led to induction of apoptosis and abrogated tumor growth in a xenograft mouse model. Recently, it was shown that NR4A inducing agents or NR4A agonist possess/induce apoptotic effects in AML and lymphoma cells. Due to this fact and the growing number of NR4A1 and NR4A3 inducing agents and NR4A agonists, both receptors represent new targets for anti tumor therapy.

  15. 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.

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

    NASA Astrophysics Data System (ADS)

    Tanak, H.

    2014-12-01

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

  17. Anthryl-1,2,4-oxadiazole-substituted calix[4]arenes as highly selective fluorescent chemodosimeters for Fe(3+).

    PubMed

    Chen, Ying-Jung; Yang, Shun-Chieh; Tsai, Chia-Chen; Chang, Kai-Chi; Chuang, Wen-Han; Chu, Wei-Lun; Kovalev, Vladimir; Chung, Wen-Sheng

    2015-04-01

    Fluorescent chemosensors 1 and 2, with 1,2,4-oxadiazoles as the binding ligands and anthracene as the fluorophore, were synthesized through sequential 1,3-dipolar cycloaddition reactions of 25,27-dioxyacetonitrilecalix[4]arenes 8 and 11. The fluorescence of 1 was severely quenched by both Fe(3+) and Cu(2+) , whereas that of 2 was selectively quenched only by Fe(3+) . Control compound 4 was also selectively quenched by Fe(3+) , which implied the importance of anthryl-1,2,4-oxadiazole core; furthermore, it was shown to give various oxidation products such as oxanthrone 13, anthraquinone 14, and imidazolyl oxanthrone 15. In addition to product separation and identification, the fluorescent quenching mechanism of these 9-anthryl-1,2,4-oxadiazolyl derivatives by Fe(3+) is also discussed. Furthermore, it should be noted that the oxadiazole-substituted anthracene 4 and calix[4]arene 2 are Fe(3+) -selective fluorescent chemodosimeters without the interference by Cu(2+) .

  18. 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)

  19. 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

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

    PubMed Central

    2014-01-01

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

  1. Synthesis and molecular structure of (4 sub 5 )(1,2,3,4,5)ferrocenophane ((4)superferrocenophane)

    SciTech Connect

    Hisatome, Masao; Watanabe, Jun; Kawajiri, Yoshiki; Yamakawa, Koji ); Iitaka, Yoichi )

    1990-02-01

    (4{sub 5})(1,2,3,4,5)Ferrocenophane, which has been given the trivial name (4)superferrocenophane, was synthesized by the stepwise construction of a tetramethylene bridge via formation of a three-carbon bridge followed by bridge enlargement. The {sup 1}H NMR spectrum showed two broad signals for the methylene resonances ({delta} 1.97 and 2.54). No other signal was present. In the {sup 13}C NMR spectrum, only three signals were observed at {delta} 87.31, 28.66, and 25.12, which were assigned to the cyclopentadienyl rings and the {alpha}- and {beta}-methylene carbons, respectively. The absorption band of d-d transition in the visible region shifted to a considerably shorter wavelength (403 nm) as compared with that of ferrocene (443 nm). The crystal structure {alpha} was determined by X-ray diffraction. Compound crystallizes in the tetragonal system, space group I42d with unit cell parameters a = 15.453 (8), c = 18.968 (10) {angstrom}, and Z = 8. The whole shape of is nearly spherical. The thermal vibrations of the {beta}-methylene carbons on the bridges are large and remarkably anisotropic. The distances between the {beta}-carbon and the adjacent carbons are unusually short (1.286 (17)-1.420 (13) {angstrom}).

  2. Calorimetric and computational study of 1,3- and 1,4-oxathiane sulfones.

    PubMed

    Roux, María Victoria; Temprado, Manuel; Jiménez, Pilar; Notario, Rafael; Guzman-Mejía, Ramón; Juaristi, Eusebio

    2007-02-16

    The enthalpies of formation in the condensed and gas states, DeltafH degrees m(cd) and DeltafH degrees m(g), of 1,3- and 1,4-oxathiane sulfones were derived from their respective enthalpies of combustion in oxygen, measured by a rotating bomb calorimeter and the variation of vapor pressures with temperatures determined by the Knudsen effusion technique. Standard ab initio molecular orbital calculations at the G2(MP2) and G3 levels were performed, and a theoretical study on molecular and electronic structure of the compounds has been carried out. Calculated DeltafH degrees m(g) values at the G3 level using atomization reactions agree well with the experimental ones. These experimental and theoretical studies support that the destabilization found in 1,3-oxathiane sulfone, 11.2 kJ mol-1 respecting to 1,4-oxathiane sulfone, is due to the electrostatic repulsion between the negative charges of the axial oxygen of the sulfone and the oxygen of the ring and apparently masks any stabilization originating from the hyperconjugative nO --> sigma*C-SO2 stereoelectronic interaction. PMID:17288369

  3. Multitasking in signal transduction by a promiscuous human Ins(3,4,5,6)P(4) 1-kinase/Ins(1,3,4)P(3) 5/6-kinase.

    PubMed

    Yang, X; Shears, S B

    2000-11-01

    We describe a human cDNA encoding 1-kinase activity that inactivates Ins(3,4,5,6)P(4), an inhibitor of chloride-channel conductance that regulates epithelial salt and fluid secretion, as well as membrane excitability. Unexpectedly, we further discovered that this enzyme has alternative positional specificity (5/6-kinase activity) towards a different substrate, namely Ins(1,3,4)P(3). Kinetic data from a recombinant enzyme indicate that Ins(1,3,4)P(3) (K(m)=0.3 microM; V(max)=320 pmol/min per microg) and Ins(3,4,5,6)P(4) (K(m)=0.1 microM; V(max)=780 pmol/min per microg) actively compete for phosphorylation in vivo. This competition empowers the kinase with multitasking capability in several key aspects of inositol phosphate signalling.

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

    PubMed

    Zeng, Wu-Lan

    2010-01-01

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

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

    SciTech Connect

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

    1986-05-01

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

  6. The Vapor Pressure of 1-(2,2,3,3-Tetrafluoropropoxy)-3-(4-sec-butylphenoxy)-2-prop anol

    SciTech Connect

    Steele, W.V.

    2002-01-29

    The vapor pressure of the compound 1-(2,2,3,3-tetrafluoropropoxy)-3-(4-sec-butylphenoxy)-2-propanol was measured over the temperature range 62 to 92 C using a Knudsen effusion technique. This compound, known as Cs-7SB, is the modifier component in the caustic-side solvent extraction process solvent. The vapor pressure is related to temperature by the equation ln(p/Pa) = (32.202 {+-} 0.265) - (12154 {+-} 93)/T, where p is the pressure, expressed in pascals; Pa is the reference pressure of 1 pascal; and T is the temperature, expressed in degrees kelvin. The derived heat of vaporization is 101.1 {+-} 0.8{sup kJ{center_dot}mol{sup 1} at 351 K. Because the vapor pressures over the temperature range of 15 to 50 C were lower than the design capabilities of the Knudsen effusion apparatus, the vapor pressures at these temperature limits were obtained by extrapolation. The estimated values are 4.6 {+-} 0.3E-05 (3.5 {+-} 0.2E-07 mm Hg) and 4.5 {+-} 0.1E-03 Pa (3.4 {+-} 0.1E-05 mm Hg) for 15 C and 50 C, respectively.

  7. C(8) substituted 1-azabicyclo[3.3.1]non-3-enes and C(8) substituted 1-azabicyclo[3.3.1]nonan-4-ones: novel muscarinic receptor antagonists.

    PubMed

    Kim, Myoung Goo; Bodor, Erik T; Wang, Chen; Harden, T Kendall; Kohn, Harold

    2003-05-22

    Expedient syntheses of C(8) substituted 1-azabicyclo[3.3.1]non-3-enes and C(8) substituted 1-azabicyclo[3.3.1]nonan-4-ones are reported to begin with 2,5-disubstituted pyridines. Catalytic reduction of the pyridine to the piperidine followed by treatment with ethyl acrylate and Dieckmann cyclization gave diastereomeric mixtures of C(8) substituted 3-ethoxycarbonyl-4-hydroxy-1-azabicyclo[3.3.1]non-3-enes, which were separable by chromatography. We found that the catalytic reduction (PtO2, H2) procedure provided the cis-substituted piperidine but that pyridine reduction was accompanied by competitive cleavage of the C(2) pyridyl substituent. Accordingly, an alternative route was devised that afforded a diastereomeric mixture of the cis- and trans-2,5-disubstituted piperidine. Treatment of the substituted pyridine with m-CPBA gave the pyridine N-oxide, which was reduced to the piperidine by sequential reduction with ammonium formate in the presence of Pd-C followed by NaBH3CN. Addition of ethyl acrylate completed the synthesis of the substituted piperidine. The overall four-step reaction gave higher yields (57%) than the two-step procedure (13%) with little cleavage of the C(2) pyridyl substituent. Acid decarboxylation of the bicyclo[3.3.1]non-3-enes provided the C(8) substituted 1-azabicyclo[3.3.1]nonan-4-ones. Structural studies revealed diagnostic 13C NMR signals that permit assignment of the orientation of the C(8) substituent. Pharmacological investigations documented that 3-ethoxycarbonyl-4-hydroxy-1-azabicyclo[3.3.1]non-3-enes efficiently bind to the human M1-M5 muscarinic receptors and function as antagonists. We observed that exo-8-benzyloxymethyl-3-ethoxycarbonyl-4-hydroxy-1-azabicyclo[3.3.1]non-3-ene (3) displayed the highest affinity, exhibiting Ki values at all five muscarinic receptors that were approximately 10-50 times lower than carbachol and approximately 30-230 times lower than arecoline. Receptor selectivity was observed for 3. Compound 3 contained

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

    SciTech Connect

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

    1989-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  10. 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

  11. 3H-2,1-Benzoxaborole-1-spiro-4′-(5-oxa-3a-aza-4-borapyrene)

    PubMed Central

    Robin, Beck; Buell, Gregg; Kiprof, Paul; Nemykin, Victor N.

    2008-01-01

    In the title compound, C20H14BNO2, the B atom has a tetra­hedral geometry with two short B—O and two long B—C and B—N bonds, revealing a significant difference between Car—O—B and Calk­yl—O—B bond distances. Inter­molecular Ar—H⋯O hydrogen bonds and strong π–π inter­actions (3.368 Å) between aromatic cores of neighbouring mol­ecules result in hexa­gonal channels along the crystallographic c axis, which are potentially accessible for small mol­ecules. PMID:21200876

  12. 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.

  13. 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…

  14. Studies on the haemolytic activity of circulating C1q-C3/C4 complexes.

    PubMed

    Wouters, Diana; Brouwer, Mieke C; Daha, Mohamed R; Hack, C Erik

    2008-04-01

    During classical complement pathway activation, the internal thio-ester of both C3 and C4 becomes exposed which enables C3 and C4 to bind covalently to nearby molecules. Recently, we described that C3 and C4 bind to C1q, the recognition molecule of the classical pathway, upon activation of this pathway. Covalently linked complexes between C1q and activated C4 (C1q-C4 complexes) are specific markers for classical complement pathway activation. In the present study we further investigated the molecular characteristics of complexes between C1q and activated C3 or C4 that occur in vivo. In human serum only complexes of C1q with C3d or C4d fragments were detected but not those with the larger C3b/bi or C4b/bi fragments. We identified that C1q-C4 complexes circulate as part of the intact C1 complex instead of as free C1q. Finally, we investigated whether deposited C3d or C4d affect C1 haemolytic activity. We observed that both C1q-C3 and C1q-C4 complexes are significantly (P<0.05) less active in a C1q-haemolytic assay than non-complexed C1q. Thus, the dominant types of C1q complexes that circulate in vivo are C1q-C3d and C1q-C4d complexes. These complexes are still able to interact with C1r and C1s to form a C1 complex, but seem to have a reduced activity as compared to C1q not carrying C3- or C4-fragments.

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...: (1) Its heat of decomposition is less than 300 J/g; or (2) Its self-accelerating decomposition... Division 5.1 containing less than 5.0% combustible organic substances; or (E) The Associate Administrator... (i.e. liquid or solid), in accordance with the definition of liquid and solid in § 171.8 of...

  16. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced Parkinson's disease in zebrafish.

    PubMed

    Sarath Babu, Nukala; Murthy, Ch Lakshmi N; Kakara, Sameera; Sharma, Rahul; Brahmendra Swamy, Cherukuvada V; Idris, Mohammed M

    2016-05-01

    Parkinson's disease (PD) is the most common age associated neurodegenerative disease, which has been extensively studied for its etiology and phenotype. PD has been widely studied in alternate model system such as rodents towards understanding the role of neurotoxin by inducing PD. This study is aimed to understand the biomechanism of PD in zebrafish model system induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The phenotype and role of various genes and proteins for Parkinsonism were tested and evaluated in this study using behavior, molecular and proteomic approaches. Zebrafish PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine showed a significant level of decrease in the movement with erratic swimming pattern and increased freezing bouts. CHCHD2, EEF2B, LRRK2, PARK7, PARK2, POLG, SNCGB and SYNB genes were differentially regulated at the transcript level in PD zebrafish. Similarly a total of 73 proteins were recognized as differentially expressed in the nervous system of zebrafish due to Parkinsonism based on quantitative proteomics approach. Proteins such as NEFL, MUNC13-1, NAV2 and GAPVD1 were down regulated in the zebrafish brain for the PD phenotype, which were associated with the neurological pathways. This zebrafish based PD model can be used as a potential model system for screening prospective drug molecules for PD. PMID:26959078

  17. 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.

  18. 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

  19. Stimulation of Inositol 1,4,5-Trisphosphate (IP3) Receptor Subtypes by Analogues of IP3

    PubMed Central

    Saleem, Huma; Tovey, Stephen C.; Rahman, Taufiq; Riley, Andrew M.; Potter, Barry V. L.; Taylor, Colin W.

    2013-01-01

    Most animal cells express mixtures of the three subtypes of inositol 1,4,5-trisphosphate receptor (IP3R) encoded by vertebrate genomes. Activation of each subtype by different agonists has not hitherto been examined in cells expressing defined homogenous populations of IP3R. Here we measure Ca2+ release evoked by synthetic analogues of IP3 using a Ca2+ indicator within the lumen of the endoplasmic reticulum of permeabilized DT40 cells stably expressing single subtypes of mammalian IP3R. Phosphorylation of (1,4,5)IP3 to (1,3,4,5)IP4 reduced potency by ∼100-fold. Relative to (1,4,5)IP3, the potencies of IP3 analogues modified at the 1-position (malachite green (1,4,5)IP3), 2-position (2-deoxy(1,4,5)IP3) or 3-position (3-deoxy(1,4,5)IP3, (1,3,4,5)IP4) were similar for each IP3R subtype. The potency of an analogue, (1,4,6)IP3, in which the orientations of the 2- and 3-hydroxyl groups were inverted, was also reduced similarly for all three IP3R subtypes. Most analogues of IP3 interact similarly with the three IP3R subtypes, but the decrease in potency accompanying removal of the 1-phosphate from (1,4,5)IP3 was least for IP3R3. Addition of a large chromophore (malachite green) to the 1-phosphate of (1,4,5)IP3 only modestly reduced potency suggesting that similar analogues could be used to measure (1,4,5)IP3 binding optically. These data provide the first structure-activity analyses of key IP3 analogues using homogenous populations of each mammalian IP3R subtype. They demonstrate broadly similar structure-activity relationships for all mammalian IP3R subtypes and establish the potential utility of (1,4,5)IP3 analogues with chromophores attached to the 1-position. PMID:23372785

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

    NASA Astrophysics Data System (ADS)

    Yu, Xiaohu; Zhang, Xuemei; Wang, Shengguang

    2015-10-01

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

  1. 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…

  2. 2-[3,4-Dibut-oxy-5-(5-phenyl-1,3,4-oxadiazol-2-yl)-2-thien-yl]-5-phenyl-1,3,4-oxadiazole.

    PubMed

    Li, Hai-Lin; Zeng, Hai-Su; Kang, Si-Shun; Wang, Hai-Bo

    2008-07-05

    In the title compound, C(28)H(28)N(4)O(4)S, the dihedral angles between the central thio-phene ring and its pendant oxadiazole rings are 1.2 (3) and 9.8 (3)°. The dihedral angles between the oxadiazole and phenyl rings are 2.9 (3) and 1.8 (3)°. Some short intra-molecular C-H⋯O contacts occur.

  3. 2-[3,4-Dibut­oxy-5-(5-phenyl-1,3,4-oxadiazol-2-yl)-2-thien­yl]-5-phenyl-1,3,4-oxadiazole

    PubMed Central

    Li, Hai-lin; Zeng, Hai-su; Kang, Si-shun; Wang, Hai-bo

    2008-01-01

    In the title compound, C28H28N4O4S, the dihedral angles between the central thio­phene ring and its pendant oxadiazole rings are 1.2 (3) and 9.8 (3)°. The dihedral angles between the oxadiazole and phenyl rings are 2.9 (3) and 1.8 (3)°. Some short intra­molecular C—H⋯O contacts occur. PMID:21203138

  4. Synthesis, antimicrobial and anti-inflammatory activities of novel 5-(1-adamantyl)-1,3,4-thiadiazole derivatives.

    PubMed

    Kadi, Adnan A; Al-Abdullah, Ebtehal S; Shehata, Ihsan A; Habib, Elsayed E; Ibrahim, Tarek M; El-Emam, Ali A

    2010-11-01

    New 1-adamanyl-1,3,4-thiadiazole derivatives namely, 5-(1-adamantyl)-1,3,4-thiadiazoline-2-thione 3, 5-(1-adamantyl)-3-(benzyl- or 4-substituted benzyl)-1,3,4-thiadiazoline-2-thione 4a-d, 5-(1-adamantyl)-3-(4-substituted-1-piperazinylmethyl)-1,3,4-thiadiazoline-2-thiones 5a-c, 2-[5-(1-adamantyl)-2-thioxo-1,3,4-thiadiazolin-3-yl]acetic acid 7, (±)-2-[5-(1-adamantyl)-2-thioxo-1,3,4-thiadiazolin-3-yl]propionic acid 9, 3-[5-(1-adamantyl)-2-thioxo-1,3,4-thiadiazolin-3-yl]propionic acid 11, N-[5-(1-adamantyl)-1,3,4-thiadiazol-2-yl]-N'-arylthioureas 15a-c and 5-(1-adamantyl)-1,3,4-thiadiazoline-2-one 16, were synthesized and tested for in vitro activities against a panel of gram-positive and gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 7, 9, 15b and 15c displayed marked activity against the tested gram-positive bacteria, while compound 3 was highly active against the tested gram-negative bacteria. Compounds 4b, 7 and 15c were weakly or moderately active against C. albicans. In addition, the in vivo anti-inflammatory activity of the synthesized compounds was determined using the carrageenan-induced paw oedema method in rats. The propionic acid derivative 9 produced good dose-dependent anti-inflammatory activity. PMID:20801553

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

    PubMed Central

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

    2001-01-01

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

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

    PubMed

    Korkmaz, Ufuk; Bulut, Iclal; Bulut, Ahmet

    2016-07-01

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

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

    PubMed Central

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

    2011-01-01

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

  8. Synthesis and antimicrobial activity of acyclo C-nucleosides: 3-(alditol-1-yl)-7-oxo-5-phenyl-1,2,4-triazolo[4,3-a]pyrimidines.

    PubMed

    Shaban, M A; Nasr, A Z; Morgaan, A E

    2000-02-01

    Condensation of 2-hydrazino-4-oxo-6-phenylpyrimidine (1) with aldopentoses 2a-d or aldohexoses 2e-g gave the corresponding aldehydo-sugar (4-oxo-6-phenylpyrimidin-2-yl)hydrazones 3a-g which were acetylated to the corresponding poly-O-acetyl-aldehydo-sugar (3-acetyl-4-oxo-6-phenylpyrimidin-2-yl)hydrazones 4a-g. The latter compounds underwent oxidative cyclization with bromine in acetic acid and in the presence of sodium acetate to the corresponding 8-acetyl-3- (poly-O-acetyl-alditol-1-yl)-7-oxo-5-phenyl-1,2,4-triazolo[4,3-a]pyrimid ines 6a-g. Compounds 6a-g were also obtained by consecutive one-pot oxidative cyclization/acetylation in which the parent hydrazones 3a-g were treated with bromine/acetic acid/sodium acetate followed by acetic anhydride. Deacetylation of 6a-g with ammonium hydroxide in methanol gave the title compounds 7a-g. The antibacterial and antifungal activities of compounds 3c, 3f, 7c and 7f are reported. PMID:10723764

  9. Synthesis and anti-inflammatory activity of 1-acylaminoalkyl-3,4-dialkoxybenzene derivatives.

    PubMed

    Labanauskas, L; Brukstus, A; Udrenaite, E; Bucinskaite, V; Susvilo, I; Urbelis, G

    2005-03-01

    New 1-acylaminoalkyl-3,4-dialkoxybenzene derivatives 17-31 were synthesized by the acylation of amines 9-16 with acyl chlorides. Amines 9-16 were obtained from aryl ketones 1-8. Aryl ketones 1-8 were synthesized by the acylation of corresponding aromatic compounds. As it was preliminary predicted by PASS (Prediction of Activity Spectra for Substance) program, all 1-acylaminoalkyl-3,4-dimethoxy- and 3,4-diethoxybenzene derivatives possess anti-inflammatory activity. Activity of compounds 18, 19, 21, 24, 26, 27, 28, 29 was similar to that of acetylsalicylic acid or ibuprofen however their acute toxicity was less than that of mentioned anti-inflammatory drugs. A series of 1-acylaminoalkyl-3,4-dimethoxybenzene, 1-acylaminoalkyl-3,4-diethoxybenzene and 6-acylaminoalkyl-2,3-dihydro-1,4-benzodioxine derivatives have been synthesized. These compounds possess moderate or strong anti-inflammatory activity and low toxicity.

  10. Flow cytometric analysis of micronucleus induction in rat bone marrow polychromatic erythrocytes by 1,2;3,4-diepoxybutane, 3,4-epoxy-1-butene, and 1,2-epoxybutane-3,4-diol.

    PubMed

    Lähdetie, J; Grawé, J

    1997-07-01

    Automation of the analysis of micronucleus induction with flow cytometry was developed by using mouse bone marrow or peripheral blood. In the present study, we report the use of flow cytometry for the identification and quantification of micronuclei (MN) induced in rat bone marrow polychromatic erythrocytes. Three metabolites of the industrial chemical 1,3-butadiene, namely 1,2;3,4-diepoxybutane (DEB), 3,4-epoxy-1-butene (EB) and 1,2-epoxybutane-3,4-diol (diol-EB), were studied in addition to mitomycin C and cyclophosphamide, which served as positive controls. DEB showed a dose-dependent increase in the frequency of MN, whereas EB was completely negative and diol-EB only weakly positive at one dose level. The effect of the positive control compounds was observed 48 h after a single injection in a dose-dependent manner. Flow cytometry was an effective method to quantitate bone marrow MN induction in the rat when density gradient separation of polychromatic erythrocytes is used. The results are compatible with the theory that oxidation of EB to the mutagenic metabolite DEB occurs at a low rate in rat bone marrow and that EB is detoxified by epoxide hydrolase and by conjugation with glutathione by glutathione transferase yielding nonmutagenic metabolites. Thus, the reported lack of MN induction by 1,3-butadiene inhalation in rat bone marrow is explained.

  11. 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.

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

    PubMed

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

    2015-04-13

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

  13. Quantitation of 1,4-Benzoxazin-3-ones in Maize by Gas-Liquid Chromatography.

    PubMed

    Woodward, M D; Corcuera, L J; Helgeson, J P; Kelman, A; Upper, C D

    1979-01-01

    A gas-liquid chromatographic (GLC) procedure is reported for the quantitation of the trimethylsilyl (TMS) derivatives of substituted 2-hydroxy-2H-1,4-benzoxazin-3(4H)-ones (2-hydroxy-2H-1,4-benzoxazin-3(4H)-one[HBOA]; 2-hydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one[HMBOA];2,4- dihydroxy-2H-1,4-benzoxazin-3(4H)-one[DIBOA]; 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one[DIMBOA]; and 2,4-dihydroxy-7,8-dimethoxy-2H-1,4-benzoxazin-3(4H)-one[DIM (2)BOA]) found in maize (Zea mays L.) extracts. Derivatized samples were chromatographed on columns with liquid phases of 2% DC-11 and 3% OV-17 and detected by flame ionization. Internal standards were methyl palmitate and methyl stearate on DC-11 and methyl behenate on OV-17. Detector response was linear to at least 5 nanomoles for TMS(2)-HBOA and TMS(2)-DIBOA and to 19 nanomoles for TMS(2)-DIMBOA. Standard errors of 2% or less were obtained when four replicate samples were analyzed. For each of the 15 maize lines examined, the amount of DIMBOA determined by GLC was directly proportional to the amount of ferric chloride-reactive material determined colorimetrically.

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

    ERIC Educational Resources Information Center

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

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

  15. STS-113 Mission Highlights Resource Tape Flight Days 1-3. Tape: 1 of 4

    NASA Technical Reports Server (NTRS)

    2003-01-01

    This video, part 1 of 4, shows the activities of the crew of Space Shuttle Endeavour during flight days 1-3 of STS-113. The crew consists of Commander Jim Wetherbee, Pilot Paul Lockhart, Mission Specialists Michael Lopez-Alegria and John Herrington. With them were the Expedition 6 crewmembers of the International Space Station (ISS), Ken Bowersox, Nikolai Budarin, and Don Pettit. Pre-launch procedures are shown, and the rain-delayed night launch is shown from several camera angles. On flight day 2 there was a check out of the Canadarm on Endeavour, and some intravehicular activity. Flight day 3 highlights the docking of Endeavour and the ISS, and preparation for an extravehicular activity (EVA) the following day. Earth views include the English Channel at night with a close-up of London, the coast of Ecuador, and some views of Endeavour with the Earth in the background.

  16. 3-(4-Bromo-benzyl-idene)-1,5-dioxaspiro-[5.5]undecane-2,4-dione.

    PubMed

    Zeng, Wu-Lan

    2011-01-01

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

  17. 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-...

  18. 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-...

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

    PubMed

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

    2016-02-15

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

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

    PubMed Central

    2015-01-01

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

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

    PubMed

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

    2016-08-01

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

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

    SciTech Connect

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

    1993-12-31

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

  3. 40 CFR 721.5225 - Naphthalene,1,2,3,4-tetra- hy-dro(1-phenylethyl) (specific name).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Naphthalene,1,2,3,4-tetra- hy-dro(1... New Uses for Specific Chemical Substances § 721.5225 Naphthalene,1,2,3,4-tetra- hy-dro(1-phenylethyl... substance naphthalene,1,2,3,4-tetrahydro(1-phenylethyl) (PMN P-85-1331) is subject to reporting under...

  4. 40 CFR 721.5225 - Naphthalene,1,2,3,4-tetra- hy-dro(1-phenylethyl) (specific name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Naphthalene,1,2,3,4-tetra- hy-dro(1... New Uses for Specific Chemical Substances § 721.5225 Naphthalene,1,2,3,4-tetra- hy-dro(1-phenylethyl... substance naphthalene,1,2,3,4-tetrahydro(1-phenylethyl) (PMN P-85-1331) is subject to reporting under...

  5. 40 CFR 721.5225 - Naphthalene,1,2,3,4-tetra- hy-dro(1-phenylethyl) (specific name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Naphthalene,1,2,3,4-tetra- hy-dro(1... New Uses for Specific Chemical Substances § 721.5225 Naphthalene,1,2,3,4-tetra- hy-dro(1-phenylethyl... substance naphthalene,1,2,3,4-tetrahydro(1-phenylethyl) (PMN P-85-1331) is subject to reporting under...

  6. 40 CFR 721.5225 - Naphthalene,1,2,3,4-tetra- hy-dro(1-phenylethyl) (specific name).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Naphthalene,1,2,3,4-tetra- hy-dro(1... New Uses for Specific Chemical Substances § 721.5225 Naphthalene,1,2,3,4-tetra- hy-dro(1-phenylethyl... substance naphthalene,1,2,3,4-tetrahydro(1-phenylethyl) (PMN P-85-1331) is subject to reporting under...

  7. 40 CFR 721.5225 - Naphthalene,1,2,3,4-tetra- hy-dro(1-phenylethyl) (specific name).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Naphthalene,1,2,3,4-tetra- hy-dro(1... New Uses for Specific Chemical Substances § 721.5225 Naphthalene,1,2,3,4-tetra- hy-dro(1-phenylethyl... substance naphthalene,1,2,3,4-tetrahydro(1-phenylethyl) (PMN P-85-1331) is subject to reporting under...

  8. Synthesis of novel 1,3,4-oxadiazole derivatives as potential antimicrobial agents.

    PubMed

    Chawla, Rakesh; Arora, Anshu; Parameswaran, Manoj Kumar; Chan, Prabodh; Sharma, Der; Michael, Sukumar; Ravi, Thengungal Kochupappy

    2010-01-01

    Some new 3-acetyl-5-(3-chloro-1-benzo[b]thiophen-2-yl)-2-substituted phenyl-2,3-dihydro-1,3,4-oxadiazoles and 2-(3-chloro-1-benzo[b]thiophen-2-yl)-5-substituted phenyl-1,3,4-oxadiazoles have been synthesized and evaluated for antimicrobial activity. Initially, 3-chloro-1-benzo[b]thiophene-2-carbonyl chloride (1) was prepared from cinnamic acid in the presence of chlorobenzene and thionyl chloride. This compound (1) was treated with hydrazine hydrate to afford 3-chloro-1-benzo[b]thiophene-2-carbohydrazine (2) which was further reacted with various aromatic aldehydes to yield hydrazones (3a-h). Further reaction of these hydrazones (3a-h) with acetic anhydride gave 3-acetyl-5-(3-chloro-1-benzo[b]thiophen-2-yl)-2-substituted phenyl-2,3-dihydro-1,3,4-oxadiazoles (4a-h). Reaction of the same compounds (3a-h) in the presence of chloramine-T afforded 2-(3-chloro-1-benzo[b]thiophen-2-yl)-5-substituted phenyl-1,3,4-oxadiazoles (5a-h). The structures of newly synthesized compounds (4a-h) and (5a-h) have been confirmed by spectroscopic techniques such as IR, 1H NMR and elemental analysis. All the compounds were screened for their antibacterial activities against Staphylococcus aureus, Bacillus subtilis. Escherichia coli and Pseudomonas aeruginosa and for antifungal activity against Candida albicans and Asperigillus niger. The compounds exhibited significant antibacterial and moderate antifungal activities. Compounds 4c and 4e were found to be most potent with activities, even better than standard drug ciprofloxacin against S. aureus and B. subtilis. PMID:20524426

  9. Synthesis, antifungal and antitumor activity of novel (Z)-5-hetarylmethylidene-1,3-thiazol-4-ones and (z)-5-ethylidene-1,3-thiazol-4-ones.

    PubMed

    Insuasty, Alberto; Ramírez, Juan; Raimondi, Marcela; Echeverry, Carlos; Quiroga, Jairo; Abonia, Rodrigo; Nogueras, Manuel; Cobo, Justo; Rodríguez, María Victoria; Zacchino, Susana A; Insuasty, Braulio

    2013-05-13

    New hetaryl- and alkylidenerhodanine derivatives 3a-d, 3e, and 4a-d were prepared from heterocyclic aldehydes 1a-d or acetaldehyde 1e. The treatment of several rhodanine derivatives 3a-d and 3e with piperidine or morpholine in THF under reflux, afforded (Z)-5-(hetarylmethylidene)-2-(piperidin-1-yl)thiazol-4(5H)-ones and 2-morpholinothiazol-4(5H)-ones 5a-d, 6a-d, and (Z)-5-ethylidene-2-morpholinothiazol-4(5H)-one (5e), respectively, in good yields. Structures of all compounds were determined by IR, 1D and 2D NMR and mass spectrometry. Several of these compounds were screened by the U.S. National Cancer Institute (NCI) to assess their antitumor activity against 60 different human tumor cell lines. Compound 3c showed high activity against HOP-92 (Non-Small Cell Lung Cancer), which was the most sensitive cell line, with GI₅₀ = 0.62 μM and LC₅₀ > 100 μM from the in vitro assays. In vitro antifungal activity of these compounds was also determined against 10 fungal strains. Compound 3e showed activity against all fungal strains tested, but showed high activity against Saccharomyces cerevisiae (MIC 3.9 μg/mL).

  10. 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.

  11. Synthesis, characterization, and antimicrobial evaluation of some new hydrazinecarbothioamide, 1,2,4-triazole and 1,3,4-thiadiazole derivatives.

    PubMed

    Güzeldemirci, Nuray Ulusoy; Satana, Dilek; Küçükbasmacı, Omer

    2013-10-01

    In this work, we reported the synthesis and evaluation of antibacterial and antifungal activities of three new compound series obtained from 6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazole-3-acetic acid hydrazide: 2-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl}-N-alkyl/arylhydrazinecarbothioamides (2a-d), 4-alkyl/aryl-2,4-dihydro-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-3H-1,2,4-triazole-3-thiones (3a-n), and 2-alkyl/arylamino-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-1,3,4-thiadiazoles (4a-g). The newly synthesized compounds were characterized by IR, (1)H NMR, (13)C NMR (APT), mass and elemental analysis. Their antibacterial and antifungal activities were evaluated against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Candida albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, Trichophyton mentagrophytes var. erinacei NCPF 375, Microsporum gypseum NCPF 580, and T. tonsurans NCPF 245. 3c, 3f, 3m, 3n, and 4e showed the highest antibacterial activity. Particularly 3c, 3f, 3g, 3k, 3n, 4a, 4e, and 4g showed the highest antifungal activity against tested fungi. PMID:22845330

  12. 26 CFR 1.702-3T - 4-Year spread (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false 4-Year spread (temporary). 1.702-3T Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Partners and Partnerships § 1.702-3T 4-Year spread (temporary). (a... taxable year for the first taxable year beginning after December 31, 1986 (partnership's year of...

  13. 26 CFR 1.702-3T - 4-Year spread (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false 4-Year spread (temporary). 1.702-3T Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Partners and Partnerships § 1.702-3T 4-Year spread (temporary). (a... taxable year for the first taxable year beginning after December 31, 1986 (partnership's year of...

  14. 26 CFR 1.702-3T - 4-Year spread (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false 4-Year spread (temporary). 1.702-3T Section 1... (CONTINUED) INCOME TAXES Partners and Partnerships § 1.702-3T 4-Year spread (temporary). (a) Applicability... year for the first taxable year beginning after December 31, 1986 (partnership's year of change);...

  15. 26 CFR 1.702-3T - 4-Year spread (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  16. Rhodium-catalyzed Carbonylation of 3-Acyloxy-1,4-enynes for the Synthesis of Cyclopentenones

    PubMed Central

    Li, Xiaoxun; Huang, Suyu; Schienebeck, Casi M.; Shu, Dongxu; Tang, Weiping

    2012-01-01

    Functionalized cyclopentenones were synthesized by a Rh-catalyzed carbonylation of 3-acyloxy-1,4-enynes, derived from alkynes and α,β-unsaturated aldehydes. The reaction involved a Saucy-Marbet 1,3-acyloxy migration of propargyl esters and a [4+1] cycloaddition of the resulting acyloxy substituted vinylallene with CO. PMID:22381143

  17. Synthesis and Biological Evaluation of a Series of 2-((1-substituted-1H-1,2,3-triazol-4-yl)methylthio)-6-(naphthalen-1-ylmethyl)pyrimidin-4(3H)-one As Potential HIV-1 Inhibitors.

    PubMed

    Fang, Zengjun; Kang, Dongwei; Zhang, Lingzi; Huang, Boshi; Liu, Huiqing; Pannecouque, Christophe; De Clercq, Erik; Zhan, Peng; Liu, Xinyong

    2015-10-01

    A series of novel S-DABO derivatives with the substituted 1,2,3-triazole moiety on the C-2 side chain were synthesized using the simple and efficient CuAAC reaction, and biologically evaluated as inhibitors of HIV-1. Among them, the most active HIV-1 inhibitor was compound 4-((4-((4-(2,6-dichlorobenzyl)-5-methyl-6-oxo-1,6-dihydropyrimidin-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)benzenesulfonamide (B5b7), which exhibited similar HIV-1 inhibitory potency (EC50  = 3.22 μm) compared with 3TC (EC50  = 2.24 μm). None of these compounds demonstrated inhibition against HIV-2 replication. The preliminary structure-activity relationship (SAR) of these new derivatives was discussed briefly.

  18. (Z)-3-(1H-Indol-3-yl)-2-(3-thienyl)acrylonitrile and (Z)-3-[1-(4-tert-butylbenzyl)-1H-indol-3-yl]-2-(3-thienyl)acrylonitrile.

    PubMed

    Sonar, Vijayakumar N; Parkin, Sean; Crooks, Peter A

    2005-02-01

    (Z)-3-(1H-Indol-3-yl)-2-(3-thienyl)acrylonitrile, C15H10N2S, (I), and (Z)-3-[1-(4-tert-butylbenzyl)-1H-indol-3-yl]-2-(3-thienyl)acrylonitrile, C26H24N2S, (II), were prepared by base-catalyzed reactions of the corresponding indole-3-carboxaldehyde with thiophene-3-acetonitrile. 1H/13C NMR spectral data and X-ray crystal structures of compounds (I) and (II) are presented. The olefinic bond connecting the indole and thiophene moieties has Z geometry in both cases, and the molecules crystallize in space groups P2(1)/c and C2/c for (I) and (II), respectively. Slight thienyl ring-flip disorder (ca 5.6%) was observed and modeled for (I).

  19. Production of a chiral alcohol, 1-(3,4-dihydroxyphenyl) ethanol, by mushroom tyrosinase.

    PubMed

    Brooks, Sarah J; Nikodinovic, Jasmina; Martin, Leona; Doyle, Evelyn M; O'Sullivan, Timothy; Guiry, Patrick J; Coulombel, Lydie; Li, Zhi; O'Connor, Kevin E

    2013-05-01

    1-(3,4-Dihydroxyphenyl) ethanol was produced biocatalytically for the first time using mushroom tyrosinase. 4-Ethylphenol at 1 mM was consumed over 12 min giving 0.23 mM 4-ethylcatechol and 0.36 mM (R/S)-1-(3,4-dihydroxyphenyl) ethanol (ee 0.5 %). Mushroom tyrosinase consumed 4-ethylphenol at 6.7 μmol min(-1) mg protein(-1) while the rates of formation of 4-ethylcatechol and 1-(3,4-dihydroxyphenyl) ethanol were 1.1 and 1.9 μmol min(-1) mg protein(-1). Addition of the ascorbic acid, as a reducing agent to biotransformation reactions, increased 4-ethylcatechol formation by 340 %. However, accumulation of 1-(3,4-dihydroxyphenyl) ethanol was not observed in the presence of ascorbic acid. While the 1-(3,4-dihydroxyphenyl) ethanol was racemic, it is the first chiral product produced by tyrosinase starting from a non-chiral substrate.

  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. 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.

  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. 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...

  4. 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...

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

    Code of Federal Regulations, 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...

  6. 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...

  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, 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...

  8. 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.

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

    PubMed

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

    2016-01-01

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

  10. 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].

  11. 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.

  12. (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

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

    PubMed

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

    2016-06-15

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

  14. Crystal structures of the co-crystalline adduct 5-(4-bromo-phen-yl)-1,3,4-thia-diazol-2-amine-4-nitro-benzoic acid (1/1) and the salt 2-amino-5-(4-bromo-phen-yl)-1,3,4-thia-diazol-3-ium 2-carb-oxy-4,6-di-nitro-phenolate.

    PubMed

    Smith, Graham; Lynch, Daniel E

    2014-11-01

    The structures of the 1:1 co-crystalline adduct C8H6BrN3S·C7H5NO4, (I), and the salt C8H7BrN3S(+)·C7H3N2O7 (-), (II), obtained from the inter-action of 5-(4-bromo-phen-yl)-1,3,4-thia-diazol-2-amine with 4-nitro-benzoic acid and 3,5-di-nitro-salicylic acid, respectively, have been determined. The primary inter-species association in both (I) and (II) is through duplex R (2) 2(8) (N-H⋯O/O-H⋯O) or (N-H⋯O/N-H⋯O) hydrogen bonds, respectively, giving heterodimers. In (II), these are close to planar [the dihedral angles between the thia-diazole ring and the two phenyl rings are 2.1 (3) (intra) and 9.8 (2)° (inter)], while in (I) these angles are 22.11 (15) and 26.08 (18)°, respectively. In the crystal of (I), the heterodimers are extended into a chain along b through an amine N-H⋯Nthia-diazole hydrogen bond but in (II), a centrosymmetric cyclic hetero-tetra-mer structure is generated through N-H⋯O hydrogen bonds to phenol and nitro O-atom acceptors and features, together with the primary R (2) 2(8) inter-action, conjoined R (4) 6(12), R (2) 1(6) and S(6) ring motifs. Also present in (I) are π-π inter-actions between thia-diazole rings [minimum ring-centroid separation = 3.4624 (16) Å], as well as short Br⋯Onitro inter-actions in both (I) and (II) [3.296 (3) and 3.104 (3) Å, respectively]. PMID:25484726

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

    SciTech Connect

    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.

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

    SciTech Connect

    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.

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

    SciTech Connect

    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.

  18. Nonlinear absorption, optical limiting behavior and structural study of a new chalcone derivative-1-(3, 4-dimethylphenyl)-3-[4(methylsulfanyl) phenyl] prop-2-en-1-one

    NASA Astrophysics Data System (ADS)

    Chandra Shekhara Shetty, T.; Raghavendra, S.; Chidan Kumar, C. S.; Dharmaprakash, S. M.

    2016-03-01

    A new third order nonlinear optical (NLO) organic material-1-(3, 4-dimethylphenyl)-3-[4(methylsulfanyl) phenyl] prop-2-en-1-one (4DPMS) belonging to chalcone family has been crystallized in acetone solution. The 4DPMS crystals are characterized by CHNS analysis, FTIR, UV-visible spectral and thermal techniques. The single crystal X-ray diffraction study reveals that 4DPMS crystallizes in monoclinic system with P21/n space group. The linear optical absorption spectrum revealed that the 4DPMS crystals are transparent in the entire visible region. Thermogravimetric data shows absence of phase transition before melting point and from differential scanning calorimetry analysis the melting point of the crystal is found to be 106 °C. Third order nonlinear absorption and optical limiting experiment on 4DPMS was carried out using open aperture Z-scan technique with Nd: YAG laser operating at 532 nm. It was found that the calculated values of excited state absorption cross section for 4DPMS molecules is much greater than the ground state absorption cross section. A decrease in effective nonlinear absorption coefficient was observed with increase in the input irradiance of laser. The observed optical limiting property in 4DPMS is attributed to reverse saturable absorption.

  19. Synthesis and Thermal Behavior of a Fused, Tricyclic 1,2,3,4-Tetrazine Ring System.

    PubMed

    Chavez, David E; Bottaro, Jeffery C; Petrie, Mark; Parrish, Damon A

    2015-10-26

    This study presents the synthesis and characterization of a fused, tricyclic 1,2,3,4-tetrazine ring system. The molecule is synthesized in a three-step process from 5,5'-dinitro-bis,1,2,4-triazole via a di-N-amino compound. Oxidation to form the azo-coupled fused tricyclic 1,2,3,4-tetrazine is achieved using tert-butyl hypochlorite as the oxidant. The di-N-amino compound and the desired fused tricyclic 1,2,3,4-triazine display interesting thermal behavior and are predicted to be high-performance energetic materials.

  20. 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

    2013-11-01

    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.

  1. Synthesis and evaluation of 3-(benzylthio)-5-(1H-indol-3-yl)-1,2,4-triazol-4-amines as Bcl-2 inhibitory anticancer agents.

    PubMed

    Hamdy, Rania; Ziedan, Noha; Ali, Samia; El-Sadek, Mohamed; Lashin, Elsaid; Brancale, Andrea; Jones, Arwyn T; Westwell, Andrew D

    2013-04-15

    A series of substituted 3-(benzylthio)-5-(1H-indol-3-yl)-4H-1,2,4-triazol-4-amines has been synthesised and tested in vitro as potential pro-apoptotic Bcl-2-inhibitory anticancer agents. Synthesis of the target compounds was readily accomplished in good yields through a cyclisation reaction between indole-3-carboxylic acid hydrazide and carbon disulfide under basic conditions, followed by S-benzylation. Active compounds, such as the nitrobenzyl analogue 6c, were found to exhibit sub-micromolar IC50 values in Bcl-2 expressing human cancer cell lines. Molecular modelling and ELISA studies further implicated anti-apoptotic Bcl-2 as a candidate molecular target underpinning anticancer activity.

  2. Synthesis of new 9-glycosyl-4,9-dihydropyrano [3,4-b]indole-1(3H)-ones as antibacterial agents.

    PubMed

    Kassab, Shaymaa E; Hegazy, Gehan H; Eid, Nahed M; Amin, Kamelia M; El-Gendy, Adel A

    2011-11-01

    A series of new 9-glycosyl-4,9-dihydropyrano[3,4-b]indole-1(3H)-ones 3 was synthesized in moderate to low yields. 4,9-Dihydropyrano[3,4-b]indole-1(3H)-ones (1) were coupled with different acetobromoglycopyranoses 2 in refluxing toluene in the presence of silver oxide to afford one coupling product of the respective N-glycosides. α-L-Arabinopyranosides 3j and 3m were the most active glycosides among the tested compounds against certain Gram positive and Gram negative bacterial strains.

  3. A dihydroxidotetracopper(II) framework supported by 4,4'-(adamantane-1,3-diyl)bis(1,2,4-triazole) and benzene-1,3,5-tricarboxylate bridges.

    PubMed

    Senchyk, Ganna A; Lysenko, Andrey B; Krautscheid, Harald; Sieler, Joachim; Domasevitch, Konstantin V

    2008-07-01

    The new bifunctional ligand 4,4'-(adamantane-1,3-diyl)bis(1,2,4-triazole) (tr(2)ad) and benzene-1,3,5-tricarboxylate sustain complementary coordination bridging for the three-dimensional framework of poly[[bis[mu(3)-4,4'-(adamantane-1,3-diyl)bis(1,2,4-triazole)-kappa(3)N(1):N(2):N(1')]bis(mu(4)-benzene-1,3,5-tricarboxylato-kappa(4)O(1):O(1'):O(3):O(5))di-mu(3)-hydroxido-kappa(6)O:O:O-tetracopper(II)] dihydrate], {[Cu(4)(C(9)H(3)O(6))(2)(OH)(2)(C(14)H(18)N(6))(2)].2H(2)O}(n). The net node is a centrosymmetric (mu(3)-OH)(2)Cu(4) cluster [Cu-O = 1.9525 (14)-2.0770 (15) A and Cu...Cu = 3.0536 (5) A] involving two independent copper ions in tetragonal pyramidal CuO(4)N and trigonal bipyramidal CuO(3)N(2) environments. One carboxylate group of the anion is bridging and the other two are monodentate, leading to the connection of three hydroxide clusters and the generation of neutral coordination layers separated by 9.3583 (5) A. The interlayer linkage is effected by mu(3)-tr(2)ad ligands, with one triazole group N(1):N(2)-bridging and the second monodentate [Cu-N = 1.9893 (19), 2.010 (2) and 2.411 (2) A]. In total, the hydroxide clusters are linked to six close neighbors within the carboxylate layer and to four neighbors via tr(2)ad bridges. Hydrogen bonding of solvent water molecules to noncoordinated triazole N atoms and carboxylate groups provides two additional links for the net, which adopts a 12-connected topology corresponding to hexagonal closest packing. The study also introduces a new type of bis(triazole) ligand, which may find wider applications for supramolecular synthesis. PMID:18599970

  4. In-vitro anti-HIV and antitumor activity of new 3,6-disubstituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and thiadiazine analogues.

    PubMed

    Al-Soud, Yaseen A; Al-Masoudi, Najim A; Loddo, Robert; La Colla, Paola

    2008-06-01

    A series of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles (7-15) and the thiadiazine analogues 16-18 have been synthesized under microwave irradiation (MWI). All synthesized compounds are evaluated for their antiviral activity against the replication of HIV-1 and HIV-2 activity in MT-4. However, compounds 12 and 18 showed EC(50) = 2.11 and 1.97 mug/mL. The results suggest that these compounds can be considered as a new lead in the development of antiviral agents. Compounds 4-18 were tested in vitro against a panel of tumor cell lines. All compounds are inactive against all the tumor sub-lines, except 10 which exhibited activity against CD4(+) human acute T-lymphoblastic leukaemia of CC(50) = 64 muM.

  5. 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.

  6. 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.

  7. 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

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

    PubMed

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

    2016-01-01

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

  9. 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.

  10. 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.

  11. 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

  12. 3-(4-Methoxybenzyl)-1,5-benzo-thiazepin-4(5H)-one.

    PubMed

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

    2013-05-01

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

  13. 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.

  14. Cytochrome P3-450 cDNA encodes aflatoxin B1-4-hydroxylase.

    PubMed

    Faletto, M B; Koser, P L; Battula, N; Townsend, G K; Maccubbin, A E; Gelboin, H V; Gurtoo, H L

    1988-09-01

    Aflatoxin B1 (AFB1), a potent hepatocarcinogen and ubiquitous dietary contaminant in some countries, is detoxified to aflatoxin M1 (AFM1) via cytochrome P-450-mediated AFB1-4-hydroxylase. Genetic studies in mice have demonstrated that the expression of AFB1-4-hydroxylase is regulated by the aryl hydrocarbon locus and suggested that different cytochrome P-450 isozymes catalyze AFB1-4-hydroxylase and aryl hydrocarbon hydroxylase activities. We have now examined lysates from mammalian cells infected with recombinant vaccinia viruses containing expressible cytochrome P1-450 or P3-450 cDNAs for their ability to metabolize AFB1 to AFM1. Our results show that cytochrome P3-450 cDNA specifies AFB1-4-hydroxylase. This is the first direct assignment of a specific cytochrome P-450 to an AFB1 detoxification pathway. This finding may have relevance to the dietary modulation of AFB1 hepatocarcinogenesis.

  15. CFP1 interacts with DNMT1 independently of association with the Setd1 Histone H3K4 methyltransferase complexes.

    PubMed

    Butler, Jill Sergesketter; Lee, Jeong-Heon; Skalnik, David G

    2008-10-01

    CXXC finger protein 1 (CFP1) is a component of the Setd1A and Setd1B methyltransferase complexes, localizes to euchromatic regions of the genome, and specifically binds unmethylated CpG dinucleotides in DNA. Murine embryos lacking CFP1 exhibit peri-implantation lethality, a developmental time that correlates with global epigenetic reprogramming. CFP1-deficient embryonic stem (ES) cells exhibit a 70% reduction in global cytosine methylation and a 60% decrease in maintenance DNA methyltransferase (DNMT1) activity. DNMT1 protein level is reduced 50% in CFP1-deficient ES cells. Experiments were performed to investigate the role of CFP1 in regulating maintenance cytosine methylation. Coimmunoprecipitation experiments reveal that endogenous DNMT1 and CFP1 interact in vivo. Protein regions required for the interaction between DNMT1 and CFP1 were mapped. Amino acids 169-493 and 970-1617 of DNMT1 are each sufficient for interaction with CFP1. Three regions spanning the CFP1 protein, amino acids 1-123, 103-367, and 361-656, are each sufficient for interaction with DNMT1. Interestingly, a single-point mutation (C375A) within CFP1 that abolishes the interaction with the Setd1A and Setd1B histone H3K4 methyltransferase complexes does not disrupt the interaction between CFP1 and DNMT1. This result indicates that CFP1 intersects the cytosine methylation machinery independently of its association with the Setd1 complexes. PMID:18680430

  16. 1,3-Diiodocalix[4]arene: synthesis by Ullmann-type iodination of 1,3-bistriflate ester of calix[4]arene, conformational analysis, and transformation into 1,3-dicarboxy-, diformyl-, and dialkylcalix[4]arenes.

    PubMed

    Tanaka, Shinya; Umetsu, Takafumi; Nebuya, Satoru; Morohashi, Naoya; Hattori, Tetsutaro

    2015-01-16

    A facile synthesis of 1,3-diiodocalix[4]arene 6 has been achieved by copper-catalyzed iodination of the 1,3-bistriflate ester 2a of p-tert-butylcalix[4]arene. After protection of the hydroxy groups with iodomethane, diiodide 6 is subjected to halogen–lithium exchange with butyllithium, followed by carbonation with CO2 or formylation with N-formylpiperidine and subsequent deprotection of the hydroxy groups to give novel dicarboxylic acid 11 or dialdehyde 16 in practical yields. The iodo groups of diiodide 6 pass through the calixarene macrocycle; the activation free energy for the conversion of the more stable syn conformer 6syn to the less stable anti conformer 6anti is ΔG(⧧) = 104 kJ mol(–1) at 298 K. Dialdehyde 16 shows fast self-exchange between two equivalent species with a cone conformation, ΔG(⧧), being 63.2 kJ mol(–1). Dicarboxylic acid 11 adopts a cone conformation and forms a dimer in solution as suggested by 1H NMR and X-ray crystallographic analyses. The arrangement of the iodide groups of compound 6 can be fixed predominantly to anti (17a and 17b) by introducing bulky alkyl groups (e.g., propyl groups) onto the hydroxy groups. The stereospecific alkylation of the iodo groups of the resulting di-O-alkylated anti-1,3-diiodides provides access to the anti-1,3-dialkylcalixarenes 19, which is otherwise difficult to obtain.

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

    PubMed

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

    2016-06-01

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

  18. 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

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

    SciTech Connect

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

    1990-08-28

    This patent describes the preparation of 1,3,5-triamino-2,4,6- trinitrobenzene (TATB) from 2,5-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.

  20. 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.

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

    PubMed

    Zeng, Wu-Lan

    2010-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-08-01

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

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

    PubMed

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

    2015-10-01

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

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

    SciTech Connect

    Paul D. Bayless

    2014-06-01

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

  5. 3,4-DGE is cytotoxic and decreases HSP27/HSPB1 in podocytes.

    PubMed

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

    2014-03-01

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

  6. 2-Sulfanylidene-1,3-dithiolo[4,5-b]naphtho-[2,3-e][1,4]dithiine-5,10-dione.

    PubMed

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

    2011-11-01

    The title mol-ecule, C(13)H(4)O(2)S(5), is folded by 47.83 (6)° along the S⋯S vector of the [1,4]dithiine six-membered ring, with the naphtho-quinone 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 inter-molecular S⋯S contacts [3.5761 (13) Å]. In the crystal structure, mol-ecules are stacked in the [100] direction, with dithiole rings making π-π inter-actions. In a stack, alternating short and long separations are observed between the centroids of dithiole rings, 3.5254 (17) and 4.7010 (18) Å.

  7. 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.

  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. PMID:26870546

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

    PubMed

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

    2004-03-01

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

  10. Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3.

    PubMed

    Li, Zhen; Chen, Weirong; Hale, Jeffrey J; Lynch, Christopher L; Mills, Sander G; Hajdu, Richard; Keohane, Carol Ann; Rosenbach, Mark J; Milligan, James A; Shei, Gan-Ju; Chrebet, Gary; Parent, Stephen A; Bergstrom, James; Card, Deborah; Forrest, Michael; Quackenbush, Elizabeth J; Wickham, L Alexandra; Vargas, Hugo; Evans, Rose M; Rosen, Hugh; Mandala, Suzanne

    2005-10-01

    A class of 3,5-diphenyl-1,2,4-oxadiazole based compounds have been identified as potent sphingosine-1-phosphate-1 (S1P1) receptor agonists with minimal affinity for the S1P2 and S1P3 receptor subtypes. Analogue 26 (S1P1 IC50 = 0.6 nM) has an excellent pharmacokinetics profile in the rat and dog and is efficacious in a rat skin transplant model, indicating that S1P3 receptor agonism is not a component of immunosuppressive efficacy.

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  12. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2006-09-01

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

  14. 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

  15. 27 CFR 555.214 - Storage within types 1, 2, 3, and 4 magazines.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  16. 27 CFR 555.214 - Storage within types 1, 2, 3, and 4 magazines.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  17. 27 CFR 555.214 - Storage within types 1, 2, 3, and 4 magazines.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  18. 27 CFR 555.214 - Storage within types 1, 2, 3, and 4 magazines.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  19. 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...

  20. (1-Ferrocenyl-4,4,4-trifluoro­butane-1,3-dionato-κ2 O,O)bis­(triphenyl­phosphane)copper(I)

    PubMed Central

    Rüffer, Tobias; Joubert, Chris C.; Buitendach, Blenerhassit E.; Swarts, Jannie C.; Jakob, Alexander; Lang, Heinrich

    2011-01-01

    In the title mononuclear coordination complex, [CuFe(C5H5)(C9H5F3O2)(C18H15P)2], the CuI ion is coordinated by the chelating β-diketonate 1-ferrocenyl-4,4,4-trifluoro­butane-1,3-dione ligand through two O atoms and the two datively bonded triphenyl­phosphane ligands resulting in a distorted tetra­hedral coordination sphere. The CuI ion, together with its chelating butane-1,3-dione group, is mutually coplanar [greatest displacement of an atom from this plane = 0.037 (1) Å], and the CuI ion lies slightly above [0.013 (1) Å] the plane. The overall geometry, including the bond distances and angles within the complex, corresponds to those of other reported copper(I) β-diketon­ates featuring organic groups at the β-diketonate ligand. PMID:21522889

  1. 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

  2. The immunosuppressive enzyme IL4I1 promotes FoxP3(+) regulatory T lymphocyte differentiation.

    PubMed

    Cousin, Céline; Aubatin, Aude; Le Gouvello, Sabine; Apetoh, Lionel; Castellano, Flavia; Molinier-Frenkel, Valérie

    2015-06-01

    IL4I1 (interleukin-4-induced gene 1) is a phenylalanine oxidase produced mainly by APCs of myeloid origin, and converts phenylalanine (Phe) to phenylpyruvate, hydrogen peroxide, and ammonia. We have previously shown that IL4I1 is highly expressed by tumor-associated macrophages from various human cancers and facilitates immune evasion from the cytotoxic response in a murine tumor model. Indeed, IL4I1 inhibits T-cell proliferation via hydrogen peroxide toxicity on effector/memory T cells. Here, we explored the effect of IL4I1 on naïve CD4(+) T-cell differentiation. We show that IL4I1 stimulates the generation of Foxp3(+) regulatory T (Treg) cells in vitro from human and mouse T cells. This effect was observed with IL4I1 from different sources, including the naturally produced enzyme. Conversely, IL4I1 limits Th1 and Th2 polarization while modifying the Th17 phenotype, in particular, by inducing its own production. Analysis of Treg-cell induction under conditions of Phe deprivation and hydrogen peroxide addition suggests that Phe consumption by the enzyme participates in Treg-cell enrichment. In line with this hypothesis, IL4I1 inhibits mTORC1 signaling shortly after T-cell activation. Thus, the IL4I1 enzyme may act on T cells both by direct inhibition of effector cell proliferation and by indirect immunoregulation mediated by Treg-cell induction.

  3. 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.

  4. Synthesis and structural characterization of 3,5-dinitro-1,2,4-triazolates.

    PubMed

    Haiges, R; Bélanger-Chabot, G; Kaplan, S M; Christe, K O

    2015-02-21

    Salts of 3,5-dinitro-1H-1,2,4-triazole, a building block for energetic materials, have been prepared and fully characterized. Most of the studied salts exhibit high thermal stability and very low shock and friction sensitivities. 3,5-Dinitro-1,2,4-triazolates with the nitrogen-rich ammonium, guanidinium, aminoguanidinium, and aminotetrazolium cations are energetic and have potential for energetic material applications. Salts containing alkali, alkali earth metal, and silver cations exhibit coloured emissions upon combustion while salts with large organic cations such as PPh4(+) and (Ph3P)2N(+) are highly insensitive and can be easily crystallized.

  5. 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).

  6. 2,4,6-Triamino-1,3,5-triazine-1H-isoindole-1,3(2H)-dione (1/3).

    PubMed

    Perpétuo, Genivaldo Júlio; Janczak, Jan

    2007-05-01

    The asymmetric unit of the title compound, C(3)H(6)N(6).3C(8)H(5)NO(2), contains a melamine and a phthalimide [1H-isoindole-1,3(2H)-dione] molecule, both residing on a mirror plane, and a second phthalimide molecule residing on a general position. The two components are linked by almost linear N-H...O and N-H...N hydrogen bonds, forming an essentially planar superstructure. These aggregates, related by a twofold screw axis, interact through weak C-H...O contacts, forming chains parallel to the b axis, while those related by translation along the c axis interact via pi-pi interactions between the pi clouds of the aromatic triazine and phthalimide rings to form a stacked structure.

  7. Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses.

    PubMed

    Alexandre, M; Uduman, A K; Minervini, S; Raoof, A; Shugrue, C A; Akinbiyi, E O; Patel, V; Shitia, M; Kolodecik, T R; Patton, R; Gorelick, F S; Thrower, E C

    2012-09-15

    Clinical studies indicate that cigarette smoking increases the risk for developing acute pancreatitis. The nicotine metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a major cigarette smoke toxin. We hypothesized that NNK could sensitize to pancreatitis and examined its effects in isolated rat pancreatic acini and in vivo. In acini, 100 nM NNK caused three- and fivefold activation of trypsinogen and chymotrypsinogen, respectively, above control. Furthermore, NNK pretreatment in acini enhanced zymogen activation in a cerulein pancreatitis model. The long-term effects of NNK were examined in vivo after intraperitoneal injection of NNK (100 mg/kg body wt) three times weekly for 2 wk. NNK alone caused zymogen activation (6-fold for trypsinogen and 2-fold for chymotrypsinogen vs. control), vacuolization, pyknotic nuclei, and edema. This NNK pretreatment followed by treatment with cerulein (40 μg/kg) for 1 h to induce early pancreatitis responses enhanced trypsinogen and chymotrypsinogen activation, as well as other parameters of pancreatitis, compared with cerulein alone. Potential targets of NNK include nicotinic acetylcholine receptors and β-adrenergic receptors; mRNA for both receptor types was detected in acinar cell preparations. Studies with pharmacological inhibitors of these receptors indicate that NNK can mediate acinar cell responses through an nonneuronal α(7)-nicotinic acetylcholine receptor (α(7)-nAChR). These studies suggest that prolonged exposure to this tobacco toxin can cause pancreatitis and sensitize to disease. Therapies targeting NNK-mediated pathways may prove useful in treatment of smoking-related pancreatitis.

  8. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  10. 1,3-Benzoxazole-4-carbonitrile as a novel antifungal scaffold of β-1,6-glucan synthesis inhibitors.

    PubMed

    Kuroyanagi, Jun-ichi; Kanai, Kazuo; Sugimoto, Yuuichi; Horiuchi, Takao; Achiwa, Issei; Takeshita, Hiroshi; Kawakami, Katsuhiro

    2010-11-01

    Synthesis and in vitro antifungal evaluations of 1,3-benzoxazole-7-carbonitrile 3, 1,3-benzoxazole-4-carbonitrile 4, benzofuran 5, benzoxazine 7, and benzimidazole 8 were reported. Among them, 1,3-benzoxazole-4-carbonitrile was found to be a superior scaffold structure with moderate growth inhibition against Candida species. 1,3-Benzoxazole-4-carbonitrile 6 showed potent activity against Candida species compared to 5-desmethyl compound 4 and triazolopyridine 2. Compound 6 was efficiently prepared from versatile intermediate 24, which possessed six different substituents on the benzene ring. Conversion of benzene 24 into various 1,3-benzoxazole derivatives such as 2-aliphatic 34, 2-amino 35, and lactone 38 was demonstrated.

  11. 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...

  12. 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).

  13. Synthesis and antitumor activity of some 2, 3-disubstituted quinazolin-4(3H)-ones and 4, 6- disubstituted- 1, 2, 3, 4-tetrahydroquinazolin-2H-ones.

    PubMed

    Abdel Gawad, Nagwa M; Georgey, Hanan H; Youssef, Riham M; El-Sayed, Nehad A

    2010-12-01

    The synthesis of some new 3-substituted quinazolin-4(3H)-ones and 3,4-dihydro-quinazolin-2(1H)-one derivatives and their biological evaluation as antitumor agents using the National Cancer Institute (NCI), disease oriented antitumor screening protocol are investigated. Compounds 2-[2-(4-chlorophenyl)-2-oxo-ethylthio]-3-(4-methoxyphenyl)quinazolin-4(3H)-one (3b), and 3-(4-chlorophenyl)-2-[2-(4-methoxyphenyl)-2-oxo-ethylthio]quinazolin-4(3H)-one (3d), are broad-spectrum antitumors showing effectiveness toward numerous cell lines that belong to different tumor subpanels, Compounds 3b, 3d are the most active members in this study. Those two quinazoline analogues could be considered as useful templates for future development to obtain more potent antitumor agent(s).

  14. Poly[(μ3-3,5-diisopropyl-4H-1,2,4-triazolato-κ3 N:N′:N′′)silver(I)

    PubMed Central

    Cui, Guo-Gen; Yang, Xiao-Xi; Yang, Jian-Ping; Jiang, Xiang

    2014-01-01

    In the polymeric title compound, [Ag(C8H14N3)]n, the AgI cation is coordinated by three N atoms from three 3,5-diisopropyl-1,2,4-triazolate anions in a T-shaped geometry. The AgI cation deviates from the coordination plane by 0.014 (1) Å and the N—Ag—N bond angles are 96.85 (11), 97.72 (10) and 165.39 (12)°. The triazolate anion bridges three AgI cations, forming a three-dimensional polymeric network. PMID:24860318

  15. 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

    2015-01-01

    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.

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

    PubMed

    Taylor, Alexander M; Vaswani, Rishi G; Gehling, Victor S; Hewitt, Michael C; Leblanc, Yves; Audia, James E; Bellon, Steve; Cummings, Richard T; Côté, Alexandre; Harmange, Jean-Christophe; Jayaram, Hari; Joshi, Shivangi; Lora, Jose M; Mertz, Jennifer A; Neiss, Adrianne; Pardo, Eneida; Nasveschuk, Christopher G; Poy, Florence; Sandy, Peter; Setser, Jeremy W; Sims, Robert J; Tang, Yong; Albrecht, Brian K

    2016-02-11

    Inhibition of the bromodomains of the BET family, of which BRD4 is a member, has been shown to decrease myc and interleukin (IL) 6 in vivo, markers that are of therapeutic relevance to cancer and inflammatory disease, respectively. Herein we report substituted benzo[b]isoxazolo[4,5-d]azepines and benzotriazolo[4,3-d][1,4]diazepines as fragment-derived novel inhibitors of the bromodomain of BRD4. Compounds from these series were potent and selective in cells, and subsequent optimization of microsomal stability yielded representatives that demonstrated dose- and time-dependent reduction of plasma IL-6 in mice. PMID:26985289

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

    PubMed Central

    Marshall, Will

    2013-01-01

    Summary The reaction of hexafluorothioacetone dimer (2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithiethane, 1) with vinylamides leads to the rapid formation of [2 + 2] cycloadducts: 4-amino-2,2-bis(trifluoromethyl)thietanes. The reaction proceeds in polar solvents (DMF, DMSO) in the absence of a catalyst at elevated temperature producing the corresponding cycloadducts in 47–86% yield. The reaction of N-vinylimidazole unexpectedly led to the formation of the corresponding 1-(hexafluoroisopropyl)-3-vinyl-1,3-dihydro-2H-imidazole-2-thione (5). The structure of this compound, along with the structures of two new thietanes was confirmed by single crystal X-ray diffraction. PMID:24367424

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. HABS ME,3SAB,1 (sheet 4 of 6) Sabbathday Lake Shaker ...

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

    HABS ME,3-SAB,1- (sheet 4 of 6) - Sabbathday Lake Shaker Community Meetinghouse, West of State Route 26, South of North Raymond Road, northwest edge of church family area, Sabbathday Lake Village, Cumberland County, ME

  3. HAER DEL,3MILF.V,2 (sheet 1 of 4) Mispillion Lighthouse, South ...

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

    HAER DEL,3-MILF.V,2- (sheet 1 of 4) - Mispillion Lighthouse, South bank of Mispillion River at its confluence with Delaware River at northeast end of County Road 203, 7 miles east of Milford, Milford, Sussex County, DE

  4. CXXC finger protein 1 restricts the Setd1A histone H3K4 methyltransferase complex to euchromatin.

    PubMed

    Tate, Courtney M; Lee, Jeong-Heon; Skalnik, David G

    2010-01-01

    CXXC finger protein 1 (Cfp1), encoded by the CXXC1 gene, is a component of the euchromatic Setd1A histone H3K4 methyltransferase complex, and is a critical regulator of histone methylation, cytosine methylation, cellular differentiation, and vertebrate development. Murine embryonic stem (ES) cells lacking Cfp1 (CXXC1(-/-)) are viable but show increased levels of global histone H3K4 methylation, suggesting that Cfp1 functions to inhibit or restrict the activity of the Setd1A histone H3K4 methyltransferase complex. The studies reported here reveal that ES cells lacking Cfp1 contain decreased levels of Setd1A and show subnuclear mislocalization of both Setd1A and trimethylation of histone H3K4 with regions of heterochromatin. Remarkably, structure-function studies reveal that expression of either the N-terminal fragment of Cfp1 (amino acids 1-367) or the C-terminal fragment of Cfp1 (amino acids 361-656) is sufficient to restore appropriate levels of Setd1A in CXXC1(-/-) ES cells. Furthermore, functional analysis of various Cfp1 point mutations reveals that retention of either Cfp1 DNA-binding activity or association with the Setd1 histone H3K4 methyltransferase complex is required to restore normal Setd1A levels. In contrast, expression of full-length Cfp1 in CXXC1(-/-) ES cells is required to restrict Setd1A and histone H3K4 trimethylation to euchromatin, indicating that both Cfp1 DNA-binding activity and interaction with the Setd1A complex are required for appropriate genomic targeting of the Setd1A complex. These studies illustrate the complexity of Cfp1 function, and identify Cfp1 as a regulator of Setd1A genomic targeting. PMID:19951360

  5. Comparative integromics on FAT1, FAT2, FAT3 and FAT4.

    PubMed

    Katoh, Yuriko; Katoh, Masaru

    2006-09-01

    WNT5A, WNT5B, WNT11, FZD3, FZD6, VANGL1, VANGL2, DVL1, DVL2, DVL3, PRICKLE1, PRICKLE2, ANKRD6, NKD1, NKD2, DAAM1, DAAM2, CELSR1, CELSR2, CELSR3, ROR1 and ROR2 are planar cell polarity (PCP) signaling molecules implicated in the regulation of cellular polarity, convergent extension, and invasion. FAT1, FAT2, FAT3 and FAT4 are Cadherin superfamily members homologous to Drosophila Fat, functioning as a positive regulator of PCP in the Drosophila wing. Complete coding sequence (CDS) for human FAT1 (NM_005245.3) and FAT2 (NM_001447.1) are available, while artificial CDS for human FAT3 (XM_926199 and XM_936538) and partial CDS for FAT4 (NM_024582.2). Here, complete CDS of human FAT3 and FAT4 were determined by using bioinformatics and human intelligence (Humint). FAT3 gene, consisting of 26 exons, encoded a 4557-aa protein with extracellular 33 Cadherin repeats, one Laminin G (LamG) domain and two EGF domains. FAT4 gene encoded a 4924-aa protein with extracellular 34 Cadherin repeats, two LamG domains and three EGF domains. Cytoplasmic VCSVxPxLP and SDYxS motifs were identified as novel motifs conserved among FAT1, FAT2 and FAT3 orthologs. Domain architecture comparison and phylogenetic analysis revealed that FAT1, FAT2 and FAR3 were divergent from FAT4. FAT1-MTNR1A locus at 4q35.2 and FAT3-MTNR1B locus at 11q14.3-q21 were paralogous regions within the human genome. FAT1 mRNA was expressed in embryonic stem (ES) cells, neural tissues, gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, lung cancer and brain tumors. FAT2 mRNA was expressed in infant brain, cerebellum, gastric cancer, pancreatic cancer, ovarian cancer, esophageal cancer, skin squamous cell carcinoma, head and neck cancer. FAT3 mRNA was expressed in ES cells, primitive neuroectoderm, fetal brain, infant brain, adult neural tissues and prostate. FAT4 mRNA was expressed in fetal brain, infant brain, brain tumor and colorectal cancer. FAT family members were revealed to be targets of systems

  6. Fragrance material review on (3aalpha,4alpha,6alpha,7alpha,7aalpha)-3a,4,5,6,7,7a-hexahydro-3-methyl-5-methylene-4,7-methano-1H-inden-6-yl acetate.

    PubMed

    Bhatia, S P; Jones, L; Letizia, C S; Api, A M

    2008-12-01

    A toxicologic and dermatologic review of (3aalpha,4alpha,6alpha,7alpha,7aalpha)-3a,4,5,6,7,7a-hexahydro-3-methyl-5-methylene-4,7-methano-1H-inden-6-yl acetate when used as a fragrance ingredient is presented.

  7. 4-(4-{[(2-Phenyl­quinazolin-4-yl)­oxy]methyl}-1H-1,2,3-triazol-1-yl)butan-1-ol hemihydrate

    PubMed Central

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

    2011-01-01

    The title compound, C21H21N5O2·0.5H2O, has two fused six-membered rings linked to a benzene ring and to a triazole ring, which is connected to a butanol group. The quinazoline ring forms a dihedral angle of 7.88 (8)° with the benzene ring, while the triazole ring is approximately perpendicular to the benzene ring and to the quinazoline system, making dihedral angles of 84.38 (10) and 76.55 (8)°, respectively. The stereochemical arrangement of the butanol chain, with a C—C—C—C torsion angle of 178.34 (19)°, corresponds to an anti­periplanar conformation. However the position of the –OH group is split into two very close [O—O = 0.810(3) Å] positions of equal occupancy. The crystal structure features O—H⋯N and O—H⋯O hydrogen bonds, building an infinite three-dimensional network. The water molecule is located on a half-filled general position. PMID:22091058

  8. 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...

  9. Analysis and Characterization of 3-(3,4-Dichlorophenyl)-1,1-Dimethylurea (DCMU)-resistant Euglena

    PubMed Central

    Calvayrac, Régis; Bomsel, Jean-Loup; Laval-Martin, Danielle

    1979-01-01

    Cultures of Euglena gracilis Klebs strain Z Pringsheim were grown photoorganotrophically in the presence of different concentrations of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) in the range of 0.05 to 250 micromolar. Cultures were serially transferred and various metabolic parameters were followed for 10 weeks. A process of adaptation occurred which was divided operationally into three phases. A phase of ultrastructural disorganization occurred, succeeded by a recovery phase; their intensity and duration were functions of the dose of DCMU. A stable adaptation phase then ensued. This phase was observed in all cultures except that exposed to the highest DCMU concentration. Adapted cells from all of the DCMU cultures contained twice the protein and half the paramylon of the control cells and thus utilized the carbon source to accumulate cellular reserves with only half the efficiency of controls. DCMU affected cellular metabolism as well as photosynthesis. The energy charge remained at high levels throughout adaptation, although the size of the adenylate pool was half that of controls at the disorganized phase. At this stage the ultrastructure of chloroplasts and mitochondria was considerably modified. The progressive changes of the parameters studied appeared to affect all of the cells in a given culture. Images PMID:16660827

  10. Analysis and Characterization of 3-(3,4-Dichlorophenyl)-1,1-Dimethylurea (DCMU)-resistant Euglena

    PubMed Central

    Calvayrac, Régis; Laval-Martin, Danielle; Dubertret, Guy; Bomsel, Jean-Loup

    1979-01-01

    When grown in medium containing dl-lactate at 27 C in the light, Euglena gracilis Z populations underwent modifications of the pigment system in response to 0.05 to 250 micromolar 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU). Chlorophyll content dropped dramatically, the only remaining form being Chl a673. Light-driven O2 evolution was no longer detectable for the two highest DCMU concentrations tested. The energy-capture cross-section of detectable photosystem II units remained unchanged, although intersystem energy transfer no longer occurred. Euglena at this stage had chloroplast membranes destacked and swollen. A recovery phase then occurred, marked by enhanced photosynthetic properties. The initial forms of chlorophyll which were accumulated were highly efficient for O2 evolution. The newly formed photosystem II antennae were connected and of small size. Finally, the third phase involved the recovery of photosynthetic capacity similar to that of the controls as the thylakoids regained their normal structures. Since these modifications occurred in the entire population and DCMU resistance persisted through successive cell generations, these adapted Euglena were considered to be a variant of the Z strain, designated ZR. PMID:16660828

  11. Crystal structure of methyl 3-(3-fluoro-phen-yl)-1-methyl-1,3a,4,9b-tetra-hydro-3H-thio-chromeno[4,3-c]isoxazole-3a-carboxyl-ate.

    PubMed

    Savithri, M P; Suresh, M; Raghunathan, R; Vimala, G; SubbiahPandi, A

    2015-08-01

    In the title compound, C19H18FNO3S, the five-membered oxazolidine ring adopts an envelope conformation with the methine C atom of the fused bond as the flap. Its mean plane is oriented at a dihedral angle of 50.38 (1)° with respect to the fluoro-phenyl ring. The six-membered thio-pyran ring has a half-chair conformation and its mean plane is almost coplanar with the fused benzene ring, making a dihedral angle of 4.94 (10)°. The two aromatic rings are inclined to one another by 85.96 (11)°, and the mean planes of the oxazolidine and thio-pyran rings are inclined to one another by 57.64 (12)°. In the crystal, mol-ecules are linked by C-H⋯π inter-actions, forming a three-dimensional structure. PMID:26396818

  12. [Overexpressing 3-ketosteroid-Δ1-dehydrogenase for degrading phytosterols into androst-1,4-diene-3,17-dione].

    PubMed

    Zhang, Lele; Zhang, Xian; Shao, Minglong; Chen, Rongrong; Rao, Zhiming; Li, Hu; Xu, Zhenghong

    2015-11-01

    We constructed plasmid pMTac to overexpress 3-ketosteroid-Δ1-dehydrogenase (KSDD) in Mycobacterium neoaurum JC-12 for improving androst-1,4-diene-3,17-dione (ADD) production. To construct pMTac, pACE promoter on pMF41 was replaced by tac promoter, and then four recombinants were constructed, which were M. neoaurum JC-12/pMF41-gfp, M. neoaurum JC-12/pMTac-gfp, M. neoaurum JC-12/pMF41-ksdd and M. neoaurum JC-12/pMTac-ksdd. Fluorescence detection results show that much more green fluorescent protein (GFP) was expressed in M. neoaurum JC-12/pMTac-ksdd than M. neoaurum JC-12/pMF41-ksdd. The activity of KSDD was 2.41 U/mg in M. neoaurum JC-12/pMTac-ksdd, 6.53-fold as that of M. neoaurum JC-12 and 4.36-fold as that of M. neoaurum JC-12/pMF41-ksdd. In shake flask fermentation, ADD production of M. neoaurum JC-12/pMTac-ksdd was 5.94 g/L, increased about 22.2% compared to the original strain M. neoaurum JC-12 and 12.7% to M. neoaurum JC-12/pMF41-ksdd. AD (4-androstene-3,17-dione) production of JC-12/pMTac-ksdd was 0.17 g/L, decreased 81.5% compared to M. neoaurum JC-12 and 71.2% to M neoaurum JC-12/pMF41-ksdd. In the 5 L fermenter, 20 g/L phytosterols was used as substrate, ADD production of M. neoaurum JC-12/pMTac-ksdd was improved to 10.28 g/L. pMTac is favorable for expressing KSDD in M. neoaurum JC-12, and overexpression of KSDD has beneficial effect on ADD producing, and it is the highest level ever reported using fermentation method in M. neoaurum. PMID:26939442

  13. Design, synthesis and biological evaluation of novel 2-[(2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazono]-1,3-thiazolidin-4-ones as a new class of antimicrobial agents.

    PubMed

    Ramachandran, R; Rani, M; Kabilan, S

    2009-05-15

    New series of 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one thiosemicarbazones (9-16) obtained from the corresponding 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones (1-8) upon cyclization with ethylbromoacetate in the presence of sodium acetate-acetic acid buffer afforded novel 2-[(2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazono]-1,3-thiazolidin-4-ones (17-24). The synthesized compounds have been characterized by their elemental, analytical and spectral studies. Besides, the reported compounds were screened for their antibacterial and antifungal activities against a spectrum of microbial organisms. These studies proved that compounds 11/18/20/23 against Staphylococcus aureus, 19/20/24 against Salmonella typhi show maximum inhibition potency at low concentration (6.25microg/ml) whereas 18/19 against Candida albicans and 19/20/21 against Rhizopus sp. showed beneficial antifungal activity at minimum concentration. PMID:19361987

  14. 5-Phenyl-3-(2-thien­yl)-1,2,4-triazolo[3,4-a]isoquinoline

    PubMed Central

    Khan, F. Nawaz; Manivel, P.; Prabakaran, K.; Hathwar, Venkatesha R.; Ng, Seik Weng

    2010-01-01

    In the title mol­ecule, C20H13N3S, the triazoloisoquinoline ring system is approximately planar, with an r.m.s. deviation of 0.045 Å and a maximum deviation of 0.090 (2) Å from the mean plane for the triazole ring C atom which is bonded to the thio­phene ring. The phenyl ring is twisted by 52.0 (1)° with respect to the mean plane of the triazoloisoquinoline ring system. The thio­phene ring is rotationally disordered by approximately 180° over two sites, the ratio of refined occupancies being 0.73 (1):0.27 (1). PMID:21579895

  15. catena-Poly[[dianilinedichloridocopper(II)]-μ(2)-2,5-bis-(4-pyrid-yl)-1,3,4-oxadiazole].

    PubMed

    Meng, Qinglong; Wu, Yiming; Zhang, Chi

    2009-01-01

    In the title compound, [CuCl(2)(C(6)H(7)N)(2)(C(12)H(8)N(4)O)](n), the Cu atom, located on an inversion center, is coordinated by four N atoms from two aniline ligands and two 2,5-bis-(4-pyrid-yl)-1,3,4-oxadiazole ligands. Two Cl atoms lying above and below the plane formed by these four N atoms inter-act weakly with the Cu atom [Cu-Cl = 2.7870 (7) Å]. The trans 2,5-bis-(4-pyrid-yl)-1,3,4-oxadiazole ligands act as bridging ligands, linking adjacent Cu atoms and forming a one-dimensional coordination polymer. Two anilines coordinate with each Cu atom as terminal groups. The structure contains two classical N-H⋯Cl and two non-classical C-H⋯Cl hydrogen bonds. PMID:21579986

  16. (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

  17. Photoionisation of Cl+ from the 3s23p4 3P2, 1, 0 and the 3s23p4 1D2, 1S0 states in the energy range 19 - 28 eV

    NASA Astrophysics Data System (ADS)

    McLaughlin, Brendan M.

    2016-10-01

    Absolute photoionisation cross sections for the Cl+ ion in its ground and the metastable states; 3s23p4 3P2, 1, 0, and 3s23p4 1D2, 1S0, were measured recently at the Advanced Light Source (ALS) at Lawrence Berkeley National Laboratory using the merged beams photon-ion technique at an photon energy resolution of 15 meV in the energy range 19 - 28 eV. These measurements are compared with large-scale Dirac Coulomb R-matrix calculations in the same energy range. Photoionisation of this sulphur-like chlorine ion is characterized by multiple Rydberg series of autoionizing resonances superimposed on a direct photoionisation continuum. A wealth of resonance features observed in the experimental spectra are spectroscopically assigned and their resonance parameters tabulated and compared with the recent measurements. Metastable fractions in the parent ion beam are determined from the present study. Theoretical resonance energies and quantum defects of the prominent Rydberg series 3s23p3nd, identified in the spectra as 3p → nd transitions are compared with the available measurements made on this element. Weaker Rydberg series 3s23p3ns, identified as 3p → ns transitions and window resonances 3s3p4(4P)np features, due to 3s → np transitions are also found in the spectra.

  18. Ubiquitin E3 ligase FIEL1 regulates fibrotic lung injury through SUMO-E3 ligase PIAS4.

    PubMed

    Lear, Travis; McKelvey, Alison C; Rajbhandari, Shristi; Dunn, Sarah R; Coon, Tiffany A; Connelly, William; Zhao, Joe Y; Kass, Daniel J; Zhang, Yingze; Liu, Yuan; Chen, Bill B

    2016-05-30

    The E3 small ubiquitin-like modifier (SUMO) protein ligase protein inhibitor of activated STAT 4 (PIAS4) is a pivotal protein in regulating the TGFβ pathway. In this study, we discovered a new protein isoform encoded by KIAA0317, termed fibrosis-inducing E3 ligase 1 (FIEL1), which potently stimulates the TGFβ signaling pathway through the site-specific ubiquitination of PIAS4. FIEL1 targets PIAS4 using a double locking mechanism that is facilitated by the kinases PKCζ and GSK3β. Specifically, PKCζ phosphorylation of PIAS4 and GSK3β phosphorylation of FIEL1 are both essential for the degradation of PIAS4. FIEL1 protein is highly expressed in lung tissues from patients with idiopathic pulmonary fibrosis (IPF), whereas PIAS4 protein levels are significantly reduced. FIEL1 overexpression significantly increases fibrosis in a bleomycin murine model, whereas FIEL1 knockdown attenuates fibrotic conditions. Further, we developed a first-in-class small molecule inhibitor toward FIEL1 that is highly effective in ameliorating fibrosis in mice. This study provides a basis for IPF therapeutic intervention by modulating PIAS4 protein abundance.

  19. Magnetoelectric and magnetic properties of aluminum borates Ho1 - x Nd x Al3(BO3)4

    NASA Astrophysics Data System (ADS)

    Volkov, N. V.; Gudim, I. A.; Demidov, A. A.; Eremin, E. V.

    2015-03-01

    The magnetoelectric and magnetic properties of substituted aluminum borates Ho1 - x Nd x Al3(BO3)4 have been studied experimentally and theoretically. A large magnetoelectric effect exceeding all known values in isostructural compounds except for HoAl3(BO3)4 has been found. The magnetoelectric polarization of Ho0.8Nd0.2Al3(BO3)4 and Ho0.5Nd0.5Al3(BO3)4 at T = 5 K in a field of 9 T is Δ P ab ( B b ) ≈ -2630 and 1380 μC/m2, respectively. A theoretical consideration based on the crystal field model for the rare-earth ion made it possible to interpret all measured properties within the unified approach. The crystal field parameters have been determined. The temperature (3-300 K) and field (up to 9 T) dependences of the magnetization and the temperature (5-100 K) and field (up to 9 T) dependences of the polarization have been described. The studied properties of Ho1 - x Nd x Al3(BO3)4 have been compared with those of HoAl3(BO3)4 demonstrating record-high polarization values.

  20. 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

  1. (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

  2. 3-Methyl-1,2,3,4,5,6,1′,2′,3′,4′-deca­hydro­spiro­[benz[f]isoquinoline-1,2′-naphthalen]-1′-one

    PubMed Central

    Siaka, Sohro; Soldatenkov, Anatoly T.; Malkova, Anastasia V.; Sorokina, Elena A.; Khrustalev, Victor N.

    2012-01-01

    The title compound, C23H23NO, is the product of a tandem transformation of the double Mannich base bis­(1-oxo-1,2,3,4-tertrahydro-2-naphtho­ylmeth­yl)amine hydro­chloride in HBr solution upon heating. The tetra­hydro­pyridine ring has a non-symmetrical half-chair conformation, whereas the cyclo­hexa­diene and cyclo­hexene rings adopt non-symmetrical half-boat conformations. The dihedral angle between the planes of the terminal benzene rings is 62.85 (6)°. The N atom has a trigonal–pyramidal geometry [sum of the bond angles = 332.4 (3)°]. In the crystal, mol­ecules form [001] chains via weak non-classical C—H⋯N hydrogen bonds. The chains are stacked along the b axis. PMID:23284532

  3. Synthesis and biological evaluation of 1-phenyl-1,2,3,4-dihydroisoquinoline compounds as tubulin polymerization inhibitors.

    PubMed

    Zheng, Can-Hui; Chen, Jun; Liu, Jia; Zhou, Xiao-Tian; Liu, Na; Shi, Duo; Huang, Jing-Jing; Lv, Jia-Guo; Zhu, Ju; Zhou, You-Jun

    2012-06-01

    A series of 1-phenyl-3,4-dihydroisoquinoline derivatives and several 1-phenyl-1,2,3,4-tetrahydroisoquinoline, 1-phenyl-isoquinoline analogues were synthesized, and their cytotoxicity and tubulin polymerization inhibitory activity were evaluated. The 1-phenyl-3,4-dihydroisoquinoline compounds were found to be potential tubulin polymerization inhibitors. Compound 5n, bearing a 3'-OH and 4'-OCH(3) substituted 1-phenyl B-ring, was shown to confer optimal bioactivity. The single-crystal structure of 5n was further determined by X-ray diffraction, and the binding mode of 5n to tubulin was obtained by molecular docking, which can explain the structure-activity relationships. The studies presented here provide a new structural type for the development of novel antitumor agents.

  4. Tissue- and cell-specific expression of Ins(1,4,5)P3 3-kinase isoenzymes.

    PubMed Central

    Vanweyenberg, V; Communi, D; D'Santos, C S; Erneux, C

    1995-01-01

    The phosphorylation of Ins(1,4,5)P3 (InsP3) to Ins(1,3,4,5)P4 (InsP4) is catalysed by InsP3 3-kinase. Molecular-biological data have shown the presence of two human isoenzymes of InsP3 3-kinase, namely InsP3 3-kinases A and B. We have isolated from a rat thymus cDNA library a 2235 bp cDNA (clone B15) encoding rat InsP3 3-kinase B. Northern-blot analysis of mRNA isolated from rat tissues (thymus, testis, brain, spleen, liver, kidney, heart, lung and intestine) revealed that a rat InsP3 3-kinase B probe hybridized to a 6 kb mRNA in lung, thymus, testis, brain and heart. In contrast, Northern-blot analysis of the same tissues probed under stringent conditions with a rat InsP3 3-kinase A probe hybridized to a 2 kb mRNA only in brain and a 1.8-2.0 kb mRNA species in testis. Northern-blot analysis of three human cell lines (HL-60, SH-SY5Y and HTB-138) probed with a human InsP3 3-kinase B probe showed the presence of a 6 kb mRNA in all cell lines, except in the human neuroblastoma cell line (SH-SY5Y), where two mRNA species of 5.7 and 6 kb were detected. Using the same blot, no hybridization signal could be seen with a human InsP3 3-kinase A probe. Altogether, our data are consistent with the notion that the two InsP3 3-kinase isoenzymes, A and B, are specifically expressed in different tissues and cells. Images Figure 3 Figure 4 PMID:7887896

  5. Crystal structure of 3-O-benzyl-4(R)-C-(1-benzyl-1H-1,2,3-triazol-4-yl)-1,2-O-iso­propyl­idene-α-d-erythro­furan­ose

    PubMed Central

    Semjonovs, Nikita; Rjabovs, Vitalijs; Stepanovs, Dmitrijs; Turks, Maris

    2015-01-01

    The title compound, C23H25N3O4, {systematic name: 1-benzyl-4-[(3aR,5R,6R,6aR)-6-benz­yloxy-2,2-di­methyl­tetra­hydro­furo[2,3-d][1,3]dioxol-5-yl]-1H-1,2,3-triazole}, consists of a substituted 2,2-di­methyl­tetra­hydro­furo[2,3-d][1,3]dioxole. The furan­ose ring adopts an envelope conformation close to C 3-exo, where the C atom substituted by the benz­yloxy group is the flap. The fused dioxolane ring also adopts an envelope conformation, with the methyl­ene C atom as the flap. In the crystal, mol­ecules are linked by weak C—H⋯O hydrogen bonds, forming zigzag chains along [010]. PMID:26870425

  6. Crystal structure of 3-O-benzyl-4(R)-C-(1-benzyl-1H-1,2,3-triazol-4-yl)-1,2-O-iso-propyl-idene-α-d-erythro-furan-ose.

    PubMed

    Semjonovs, Nikita; Rjabovs, Vitalijs; Stepanovs, Dmitrijs; Turks, Maris

    2015-12-01

    The title compound, C23H25N3O4, {systematic name: 1-benzyl-4-[(3aR,5R,6R,6aR)-6-benz-yloxy-2,2-di-methyl-tetra-hydro-furo[2,3-d][1,3]dioxol-5-yl]-1H-1,2,3-triazole}, consists of a substituted 2,2-di-methyl-tetra-hydro-furo[2,3-d][1,3]dioxole. The furan-ose ring adopts an envelope conformation close to C 3-exo, where the C atom substituted by the benz-yloxy group is the flap. The fused dioxolane ring also adopts an envelope conformation, with the methyl-ene C atom as the flap. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, forming zigzag chains along [010].

  7. Synthesis and Anticonvulsant Activity Evaluation of 4-Phenyl-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one and Its Derivatives.

    PubMed

    Zhang, Hong-Jian; Jin, Peng; Wang, Shi-Ben; Li, Fu-Nan; Guan, Li-Ping; Quan, Zhe-Shan

    2015-08-01

    A series of 4-(substituted-phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones (6a-x) with triazole and other heterocyclic substituents (7-14) were synthesized and the compounds were evaluated for their anticonvulsant activity and neurotoxicity by maximal electroshock (MES) and rotarod neurotoxicity tests. Among the compounds studied, 6o and 6q showed wide margins of safety with protective indices (PIs) that were much higher than those of currently used drugs (PI6o  > 25.5, PI6q  > 26.0). Compounds 6o and 6q showed significant oral activity against MES-induced seizures in mice, with ED50 values of 88.02 and 94.6 mg/kg, respectively. The two compounds were also found to have potent activity against seizures that were induced by pentylenetetrazole and bicuculline.

  8. A food-grade industrial arming yeast expressing β-1,3-1,4-glucanase with enhanced thermal stability*

    PubMed Central

    Guo, Qin; Zhang, Wei; Ma, Liu-liu; Chen, Qi-he; Chen, Ji-cheng; Zhang, Hong-bo; Ruan, Hui; He, Guo-qing

    2010-01-01

    The aim of this work was to construct a novel food-grade industrial arming yeast displaying β-1,3-1,4-glucanase and to evaluate the thermal stability of the glucanase for practical application. For this purpose, a bi-directional vector containing galactokinase (GAL1) and phosphoglycerate kinase 1 (PGK1) promoters in different orientations was constructed. The β-1,3-1,4-glucanase gene from Bacillus subtilis was fused to α-agglutinin and expressed under the control of the GAL1 promoter. α-galactosidase induced by the constitutive PGK1 promoter was used as a food-grade selection marker. The feasibility of the α-galactosidase marker was confirmed by the growth of transformants harboring the constructed vector on a medium containing melibiose as a sole carbon source, and by the clear halo around the transformants in Congo-red plates owing to the expression of β-1,3-1,4-glucanase. The analysis of β-1,3-1,4-glucanase activity in cell pellets and in the supernatant of the recombinant yeast strain revealed that β-1,3-1,4-glucanase was successfully displayed on the cell surface of the yeast. The displayed β-1,3-1,4-glucanase activity in the recombinant yeast cells increased immediately after the addition of galactose and reached 45.1 U/ml after 32-h induction. The thermal stability of β-1,3-1,4-glucanase displayed in the recombinant yeast cells was enhanced compared with the free enzyme. These results suggest that the constructed food-grade yeast has the potential to improve the brewing properties of beer. PMID:20043351

  9. 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.

  10. 6,7-Dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinolines as superior reversal agents for P-glycoprotein-mediated multidrug resistance.

    PubMed

    Liu, Baomin; Qiu, Qianqian; Zhao, Tianxiao; Jiao, Lei; Li, Yunman; Huang, Wenlong; Qian, Hai

    2015-02-01

    P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle for successful cancer chemotherapy. Based on our previous study, 17 novel compounds with the 6,7-dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinoline scaffold were designed and synthesized. Among them, 2-[(1-{4-[2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl]phenyl}-1H-1,2,3-triazol-4-yl)methoxy]-N-(p-tolyl)benzamide (compound 7 h) was identified as a potent modulator of P-gp-mediated MDR, with high potency (EC50 =127.5 ± 9.1 nM), low cytotoxicity (TI>784.3), and long duration (>24 h) in reversing doxorubicin (DOX) resistance in K562/A02 cells. Compound 7 h also enhanced the effects of other MDR-related cytotoxic agents (paclitaxel, vinblastine, and daunorubicin), increased the accumulation of DOX and blocked P-gp-mediated rhodamine 123 efflux function in K562/A02 MDR cells. Moreover, 7 h did not have any effect on cytochrome (CYP3A4) activity. These results indicate that 7 h is a relatively safe modulator of P-gp-mediated MDR that has good potential for further development.

  11. Biosynthesis of the Halogenated Auxin, 4-Chloroindole-3-Acetic Acid1[W][OA

    PubMed Central

    Tivendale, Nathan D.; Davidson, Sandra E.; Davies, Noel W.; Smith, Jason A.; Dalmais, Marion; Bendahmane, Abdelhafid I.; Quittenden, Laura J.; Sutton, Lily; Bala, Raj K.; Le Signor, Christine; Thompson, Richard; Horne, James; Reid, James B.; Ross, John J.

    2012-01-01

    Seeds of several agriculturally important legumes are rich sources of the only halogenated plant hormone, 4-chloroindole-3-acetic acid. However, the biosynthesis of this auxin is poorly understood. Here, we show that in pea (Pisum sativum) seeds, 4-chloroindole-3-acetic acid is synthesized via the novel intermediate 4-chloroindole-3-pyruvic acid, which is produced from 4-chlorotryptophan by two aminotransferases, TRYPTOPHAN AMINOTRANSFERASE RELATED1 and TRYPTOPHAN AMINOTRANSFERASE RELATED2. We characterize a tar2 mutant, obtained by Targeting Induced Local Lesions in Genomes, the seeds of which contain dramatically reduced 4-chloroindole-3-acetic acid levels as they mature. We also show that the widespread auxin, indole-3-acetic acid, is synthesized by a parallel pathway in pea. PMID:22573801

  12. cis-1,3,4,6-Tetranitrooctahydroimidazo-[4,5-d]imidazole (BCHMX), its properties and initiation reactivity.

    PubMed

    Klasovitý, Dusan; Zeman, Svatopluk; Růzicka, Ales; Jungová, Marcela; Rohác, Michal

    2009-05-30

    Using the (15)N NMR chemical shifts of nitrogen atoms in nitramino groups of cis-1,3,4,6-tetranitrooctahydroimidazo-[4,5-d]imidazole (bicyclo-HMX or BCHMX) and additional 10 nitramines, we have assessed its reactivity in detonation, under the influence of impact, and by action of electric spark. It is stated that the thermal stability of BCHMX is higher than that of 1,3,5-trinitro-1,3,5-triazinane (RDX). The longest NN bond in the BCHMX molecule (1.412(4)A) is the cause for its higher impact reactivity, which is at the level of that of penterythritol tetranitrate (PETN). In the experimentally determined detonation velocity, BCMX can be slightly better performing than RDX. From the standpoint of friction sensitivity, BCHMX is similar to 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX). Attention was also focused on the solubility-temperature dependence of BCHMX in acetone, acetonitrile, ethyl acetate, dimethyl sulfoxide, tetrahydrofurane, and nitromethane. X-ray crystallographic study of BCHMX (C(4)H(6)N(8)O(8), M(r)=294.17), has been carried out at the temperature of 150K with the following results: a=8.5430(8), b=6.9480(6), c=8.7780(8)A, alpha=90.0(7) degrees , beta=102.452(11) degrees , gamma=90.0(9) degrees , V=508.777(8)A(3), Z=2, D(x)=1.920 g cm(-3), lambda(Mo Ka)=0.71073A, micro=0.169 cm(-1), F(000)=856, final R=0.0414 for 1254 independent observed reflections. In the BCHMX crystal there were found more short contacts in the molecular crystal of BCHMX data of Gilardi creating extensive supramolecular architecture.

  13. Copper-catalyzed Huisgen 1,3-dipolar cycloaddition under oxidative conditions: polymer-assisted assembly of 4-acyl-1-substituted-1,2,3-triazoles.

    PubMed

    Diz, Paula M; Coelho, Alberto; El Maatougui, Abdelaziz; Azuaje, Jhonny; Caamaño, Olga; Gil, Álvaro; Sotelo, Eddy

    2013-07-01

    We herein document the first example of a reliable copper-catalyzed Huisgen 1,3-dipolar cycloaddition under oxidative conditions. The combined use of two polymer-supported reagents (polystyrene-1,5,7-triazabicyclo[4,4,0]dec-5-ene/Cu and polystyrene-2-iodoxybenzamide) overcomes the thermodynamic instability of copper(I) species toward oxidation, enabling the reliable Cu-catalyzed Huisgen 1,3-dipolar cycloadditions in the presence of an oxidant agent. This polymer-assisted pathway, not feasible under conventional homogeneous conditions, provides a direct assembly of 4-acyl-1-substituted-1,2,3-triazoles, contributing to expand the reliability and scope of Cu(I)-catalyzed alkyne-azide cycloaddition.

  14. Aberrant RSPO3-LGR4 signaling in Keap1-deficient lung adenocarcinomas promotes tumor aggressiveness.

    PubMed

    Gong, X; Yi, J; Carmon, K S; Crumbley, C A; Xiong, W; Thomas, A; Fan, X; Guo, S; An, Z; Chang, J T; Liu, Q J

    2015-09-01

    The four R-spondins (RSPO1-4) and their three related receptors LGR4, 5 and 6 (LGR4-6) have emerged as a major ligand-receptor system with critical roles in development and stem cell survival through modulation of Wnt signaling. Recurrent, gain-of-expression gene fusions of RSPO2 (to EIF3E) and RSPO3 (to PTPRK) occur in a subset of human colorectal cancer. However, the exact roles and mechanisms of the RSPO-LGR system in oncogenesis remain largely unknown. We found that RSPO3 is aberrantly expressed at high levels in approximately half of Keap1-mutated lung adenocarcinomas (ADs). This high RSPO3 expression is driven by a combination of demethylation of its own promoter region and deficiency in Keap1 instead of gene fusion as in colon cancer. Patients with RSPO3-high tumors (~9%, 36/412) displayed much poorer survival than the rest of the cohort (median survival of 28 vs 163 months, log-rank test P<0.0001). Knockdown (KD) of RSPO3, LGR4 or their signaling mediator IQGAP1 in lung cancer cell lines with Keap1 deficiency and high RSPO3-LGR4 expression led to reduction in cell proliferation and migration in vitro, and KD of LGR4 or IQGAP1 resulted in decrease in tumor growth and metastasis in vivo. These findings suggest that aberrant RSPO3-LGR4 signaling potentially acts as a driving mechanism in the aggressiveness of Keap1-deficient lung ADs.

  15. Aberrant RSPO3-LGR4 signaling in Keap1-deficient lung adenocarcinomas promotes tumor aggressiveness

    PubMed Central

    Gong, Xing; Yi, Jing; Carmon, Kendra S.; Crumbley, Christine A.; Xiong, Wei; Thomas, Anthony; Fan, Xuejun; Guo, Shan; An, Zhiqiang; Chang, Jeffrey T.; Liu, Qingyun J.

    2015-01-01

    The four R-spondins (RSPO1-4) and their three related receptors LGR4, 5 and 6 (LGR4-6) have emerged as a major ligand-receptor system with critical roles in development and stem cell survival through modulation of Wnt signaling. Recurrent, gain-of-expression gene fusions of RSPO2 (to EIF3E) and RSPO3 (to PTPRK) occur in a subset of human colorectal cancer. However, the exact roles and mechanisms of the RSPO-LGR system in oncogenesis remain largely unknown. We found that RSPO3 is aberrantly expressed at high levels in approximately half of the Keap1-mutated lung adenocarcinomas. This high RSPO3 expression is driven by a combination of demethylation of its own promoter region and deficiency in Keap1 instead of gene fusion as in colon cancer. Patients with RSPO3-high tumors (~9%, 36/412) displayed much poorer survival than the rest of the cohorts (median survival of 28 vs. 163 months, logrank test p < 0.0001). Knockdown of RSPO3, LGR4, or their signaling mediator IQGAP1 in lung cancer cell lines with Keap1 deficiency and high RSPO3-LGR4 expression led to reduction in cell proliferation and migration in vitro, and knockdown of LGR4 or IQGAP1 resulted in decrease in tumor growth and metastasis in vivo. These findings suggest that aberrant RSPO3-LGR4 signaling potentially acts as a driving mechanism in the aggressiveness of Keap1-deficient lung adenocarcinomas. PMID:25531322

  16. N-(3,4-Dimethyl-phen-yl)-4-hydr-oxy-2-methyl-2H-1,2-benzothia-zine-3-carboxamide 1,1-dioxide.

    PubMed

    Siddiqui, Waseeq Ahmad; Ali, Muhammad; Zia-Ur-Rehman, Muhammad; Sharif, Saima; Tizzard, Graham John

    2009-03-28

    1,2-Benzothia-zines similar to the title compound, C(18)H(18)N(2)O(4)S, are well known in the literature for their biological activities and are used as medicines in the treatment of inflammation and rheumatoid arthritis. The thia-zine ring adopts a distorted half-chair conformation. The enolic H atom is involved in an intra-molecular O-H⋯O hydrogen bond, forming a six-membered ring. In the crystal, mol-ecules arrange themselves into centrosymmetric dimers by means of pairs of weak inter-molecular N-H⋯O hydrogen bonds.

  17. 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...

  18. Inhibition of monoamine oxidase by 3,4-dihydro-2(1H)-quinolinone derivatives.

    PubMed

    Meiring, Letitia; Petzer, Jacobus P; Petzer, Anél

    2013-10-15

    In the present study, a series of 3,4-dihydro-2(1H)-quinolinone derivatives were synthesized and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The 3,4-dihydro-2(1H)-quinolinone derivatives are structurally related to a series of coumarin (1-benzopyran-2-one) derivatives which have been reported to act as MAO-B inhibitors. The results document that the quinolinones are highly potent and selective MAO-B inhibitors with most homologues exhibiting IC50 values in the nanomolar range. The most potent MAO-B inhibitor, 7-(3-bromobenzyloxy)-3,4-dihydro-2(1H)-quinolinone, exhibits an IC50 value of 2.9 nM with a 2750-fold selectivity for MAO-B over the MAO-A isoform. An analysis of the structure-activity relationships for MAO-B inhibition shows that substitution on the C7 position of the 3,4-dihydro-2(1H)-quinolinone scaffold leads to significantly more potent inhibition compared to substitution on C6. In this regard, a benzyloxy substituent on C7 is more favourable than phenylethoxy and phenylpropoxy substitution on this position. It may be concluded that C7-substituted 3,4-dihydro-2(1H)-quinolinones are promising leads for the therapy of Parkinson's disease.

  19. 2,3-Dibromo-3-(4-chloro­phen­yl)-1-(4-nitro­thio­phen-2-yl)propan-1-one

    PubMed Central

    Fun, Hoong-Kun; Arshad, Suhana; Shetty, Shobhitha; Kalluraya, Balakrishna; Babu, M.

    2012-01-01

    The title compound, C13H8Br2ClNO3S, exhibits whole-mol­ecule disorder over two orientations in a 0.805 (6):0.195 (6) ratio. The dihedral angles between the thio­phene ring [maximum deviations = 0.017 (4) and 0.033 (9) Å for the major and minor components, respectively] and the chloro-substituted phenyl ring are 32.1 (5) (major component) and 26.3 (18)° (minor component). In the crystal, C—H⋯Cl and C—H⋯O hydrogen bonds link the mol­ecules into sheets lying parallel to the bc plane. Aromatic π–π stacking inter­actions [centroid–centroid distance = 3.550 (7) Å] are also observed. PMID:22969574

  20. Synthesis and analgesic activity of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones and 3-(substituted phenyl)-1,2,3-triazolo[4,5-b]pyridines.

    PubMed

    Clark, R L; Pessolano, A A; Shen, T Y; Jacobus, D P; Jones, H; Lotti, V J; Flataker, L M

    1978-09-01

    In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the pain thresholds of both the inflamed and normal foot were elevated. This is not commonly observed with nonsteroidal antiinflammatory agents. The most active compounds were 1,3-dihydro-3[3,4-(methylenedioxy)phenyl]imidazo[4,5-b]pyridin-2-one (I-15) and its N-allyl (I-21) and N-isopropyl (I-121) derivatives. In the triazole series the 3-(2-fluoro- and 2,4-difluorophenyl)triazolo[4,5-b]pyridines (T-1 and T-8) were the best. The imidazole compounds were somewhat superior in analgesic activity to codeine and d-propoxyphene without showing any narcotic characteristics. Some of the compounds also possessed activity against carrageenan-induced foot edema in the rat, so these compounds represent a new class of nonnarcotic analgesic antiinflammatories, capable of producing a greater degree of analgesia than that obtainable with other nonsteroidal antiinflammatory agents.

  1. Synthesis of Novel Pyrido[4,3-e][1,2,4]triazino[3,2-c][1,2,4]thiadiazine 6,6-dioxide Derivatives with Potential Anticancer Activity.

    PubMed

    Sławiński, Jarosław; Grzonek, Aleksandra; Żołnowska, Beata; Kawiak, Anna

    2015-01-01

    A series of novel 3-/2,3-substituted pyrido[4,3-e][1,2,4]triazino[3,2-c][1,2,4]thiadiazine 6,6-dioxides 4-28 have been synthesized by the reaction of 3-amino-2-(4-thioxo-1,4-dihydropyridin-3-yl-sulfonyl)guanidine with either 2-oxoalkanoic acids and its esters, or phenylglyoxylic hydrates in glacial acetic acid. Some of them exhibited reasonable or moderate anticancer activity toward human cancer cell lines, HCT-116, MCF-7 and HeLa. The structure of this novel heterocyclic ring system was confirmed by ¹D-NMR and ²D-NMR spectroscopic data including COSY, ROESY and HMBC, elemental analyses and MS spectrometry. PMID:26729078

  2. Crystal structure of 2-amino-3-cyano-4-(4-meth-oxy-phen-yl)-4H-1-benzo-thieno[3,2-b]pyran.

    PubMed

    Bakhouch, Mohamed; El Yazidi, Mohamed; Kerbal, Abdelali; Saadi, Mohamed; El Ammari, Lahcen

    2015-12-01

    The three fused five- and six-membered rings in the title compound, C19H14N2O2S, are virtually coplanar, with the maximum deviation from the mean plane being 0.060 (1) Å. This benzothieno[3,2-b]pyran ring system is nearly perpendic-ular to the plane of the 4-meth-oxy-phenyl ring, forming a dihedral angle of 83.65 (5)°. In the crystal, mol-ecules are linked by pairs of N-H⋯N hydrogen bonds into inversion dimers. The dimeric units are further connected by an N-H⋯O hydrogen bond into a tape running along the b axis. The tapes are linked together by C-H⋯N and π-π inter-actions [centroid-centroid distance = 3.7743 (8) Å], forming a three-dimensional network. PMID:26870489

  3. Potassium 3-oxo-2,3-dihydro-1H-inden-4-olate: Formation, molecular and electronic structure

    NASA Astrophysics Data System (ADS)

    Sigalov, Mark; Shainyan, Bagrat; Sterkhova, Irina

    2016-11-01

    Unlike 1-indanone, 7-hydroxy-1-indanone does not enter the base-catalyzed condensation reaction with 1H-pyrrole-2-carbaldehyde but, instead, gives the salt, potassium 3-oxo-2,3-dihydro-1H-inden-4-olate dihydrate. X-ray analysis, NMR, IR, UV spectroscopy, DFT and MP2 calculations allowed to prove the chelate structure of the salt and to estimate the effect of chelation on the spectral properties as well as to explain the specific reactivity.

  4. 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.

  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. Total syntheses of the elusive welwitindolinones with bicyclo[4.3.1] cores.

    PubMed

    Huters, Alexander D; Styduhar, Evan D; Garg, Neil K

    2012-04-16

    The welwitindolinones with bicyclo[4.3.1] cores are a class of natural products that have attracted tremendous interest from the synthetic community because of their fascinating structures and promising biological profiles. More than 15 research groups worldwide have reported progress toward these elusive natural products. This Minireview describes contemporary studies aimed at the total synthesis of these challenging targets, in addition to the two recently completed syntheses of welwitindolinones with bicyclo[4.3.1] cores reported by Rawal and Garg in 2011. Both of the completed efforts rely on C4-C11 bond constructions to access the congested bicyclic framework of these elusive natural products.

  7. 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.

  8. 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.

  9. 2,2-Dimethyl-5-(2,3,4-trimeth-oxy-benzyl-idene)-1,3-dioxane-4,6-dione.

    PubMed

    Zeng, Wu-Lan

    2011-08-01

    The title compound, C(16)H(18)O(7), was prepared by the reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione and 2,3,4-trimeth-oxy-benzaldehyde. The 1,3-dioxane ring is in a slightly distorted boat conformation. The crystal structure is stabilized by weak inter-molecular C-H⋯O hydrogen bonds. PMID:22090981

  10. 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).

  11. Neutrino mass and mixing in the 3-3-1 model with neutral leptons based on D4 flavor symmetry

    NASA Astrophysics Data System (ADS)

    Vien, V. V.

    2014-07-01

    We propose a new D4 flavor model based on SU(3)C⊗SU(3)L ⊗U(1)X gauge symmetry responsible for fermion masses and mixings in which all fermion fields act only as singlets under D4 which differs from our previous work. The neutrinos get small masses from two SU(3)L anti-sextets and one SU(3)L triplet which are all in singlets under D4. If a SU(3)L Higgs triplet, lying in {1}''' under D4, is considered as a perturbation the corresponding neutrino mass mixing matrix gets the most general form. In this case, the model can fit the most recent data on neutrino masses and mixing with nonzero θ13. Our results show that the neutrino masses are naturally small. The sum of three light neutrino masses and the effective mass governing neutrinoless double beta decay are obtained that are consistent with the recent data.

  12. 1,2,3-thiadiazole thioacetanilides. Part 2: Synthesis and biological evaluation of a new series of 2-{[4-(3,4-dichlorophenyl)-1,2,3-thiadiazol-5-yl]sulfanyl}acetanilides as HIV-1 inhibitors.

    PubMed

    Zhan, Peng; Liu, Xin-Yong; Li, Zhen-Yu; Fang, Zeng-Jun; Pannecouque, Christophe; De Clercq, Erik

    2010-07-01

    As part of our studies to discover new HIV-1 reverse transcriptase inhibitors, a series of 3,4-dichlorophenyl substituted 1,2,3-thiadiazole thioacetanilide (TTA=[(1,2,3-thiadiazole-5-yl)sulfanyl]acetanilide) derivatives were synthesized, and in vitro anti-HIV activity was evaluated. The results revealed that nearly half of the compounds show moderate-to-good inhibitory potency against HIV-1. In particular, compound 7f is highly potent, with an EC(50) value of 0.95+/-0.33 microM. The preliminary structure-activity relationship among the newly synthesized congeners is discussed. PMID:20658659

  13. Synthesis and Pharmacological Evaluation of Novel 1-(1,4-Alkylaryldisubstituted-4,5-dihydro-1H-imidazo)-3-substituted Urea Derivatives.

    PubMed

    Szacoń, Elżbieta; Rządkowska, Marzena; Kaczor, Agnieszka A; Kędzierska, Ewa; Orzelska-Górka, Jolanta; Fidecka, Sylwia; Matosiuk, Dariusz

    2016-01-01

    Novel 1-(1,4-alkylaryldisubstituted-4,5-dihydro-1H-imidazo)-3-substituted urea derivatives have been synthesized and evaluated for their central nervous system activity. Compounds 3a-m were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a-c and appropriate isocyanates 2 in dichloromethane. The compounds were subjected to in silico ADMET studies in order to select best candidates for in vivo experiments. The effects of the compounds on the spontaneous locomotor activity and amphetamine-evoked hyperactivity were estimated. Analgesic activity, without or in the presence of naloxone, was assessed in the writhing test. The tendency to change the HTR, evoked by l-5-HTP and the involvement in alteration in body temperature in mice was studied. Additionally, to check possible occurrence of drug-induced changes in the muscle relaxant activity of mice, which may have contributed to their behaviour in other tests, the rota-rod and chimney tests were performed. The new urea derivatives exerted significant activities in the performed pharmacological tests, although the presented results show a preliminary estimation, and thus, need to be extended for identification and understanding the complete pharmacological profile of the examined compounds. PMID:27144554

  14. dRAGging Amino Acid-mTORC1 Signaling by SH3BP4

    PubMed Central

    Kim, Young-Mi; Kim, Do-Hyung

    2013-01-01

    Mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth and autophagy. Its activity is regulated by the availability of amino acids and growth factors. The activation of mTORC1 by growth factors, such as insulin and insulin-like growth factor-1 (IGF-1), is mediated by tuberous sclerosis complex (TSC) 1 and 2 and Rheb GTPase. Relative to the growth factor-regulated mTORC1 pathway, the evolutionarily ancient amino acid-mTORC1 pathway remains not yet clearly defined. The amino acid-mTORC1 pathway is mediated by Rag GTPase heterodimers. Several binding proteins of Rag GTPases were discovered in recent studies. Here, we discuss the functions and mechanisms of the newly-identified binders of Rag GTPases. In particular, this review focuses on SH3 binding protein 4 (SH3BP4), the protein recently identifed as a negative regulator of Rag GTPases. PMID:23274731

  15. Rapid transformation of 1,2,3,4-TCDD by Pd/Fe catalysts.

    PubMed

    Wang, Zhiyuan; Huang, Weilin; Peng, Ping'an; Fennell, Donna E

    2010-01-01

    This study investigated reductive dechlorination of 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD) in the presence of Pd/Fe, Cu/Fe and Ni/Fe bimetallic catalysts or zero-valent iron (ZVI) under aqueous and ambient temperature conditions. It was found that the Pd/Fe catalyst can rapidly transform 1,2,3,4-TCDD to chlorine-free dibenzo-p-dioxin (DD) with >95% of conversion and half lives on the order of 5h, whereas Cu/Fe, Ni/Fe and ZVI were not reactive over 10d. The dechlorination of 1,2,3,4-TCDD in the Pd/Fe systems was found to be stepwise, with 1,2,3-tri (TrCDD), 1,2-di (DCDD), and mono-(MCDD) chlorodibenzo-p-dioxins as the three intermediate products at low concentrations and DD as the final and dominant product. The reaction rate of 1,2,3,4-TCDD dechlorination appeared to decrease as the coverage of palladium on iron particle surface increases from 0.0060 mol% to 0.0228 mol%. Compared to our prior study of reductive dechlorination of 1,2,3,4-TCDD with zero valent zinc (ZVZ) as the reductant, the reactions with Pd/Fe bimetallic materials were relatively slower for TCDD, but much faster for TrCDDs and DCDDs, yielding DD as the major product. The study suggested that Pd/Fe bimetallic catalyst-based reactions may be suitable for rapid decontamination of polychlorinated dibenzo-p-dioxin/dibenzofuran (PCDD/F) polluted soils and sediments.

  16. (3Z)-3-(2-[4-(aryl)-1,3-thiazol-2-yl]hydrazin-1-ylidene)-2,3-dihydro-1H-indol-2-one derivatives as dual inhibitors of HIV-1 reverse transcriptase.

    PubMed

    Meleddu, Rita; Distinto, Simona; Corona, Angela; Bianco, Giulia; Cannas, Valeria; Esposito, Francesca; Artese, Anna; Alcaro, Stefano; Matyus, Peter; Bogdan, Dora; Cottiglia, Filippo; Tramontano, Enzo; Maccioni, Elias

    2015-03-26

    The HIV-1 Reverse Transcriptase (RT) is a validated and deeply explored biological target for the treatment of AIDS. However, only drugs targeting the RT-associated DNA polymerase (DP) function have been approved for clinical use. We designed and synthesised a new generation of HIV-1 RT inhibitors, based on the (3Z)-3-(2-[4-(aryl)-1,3-thiazol-2-yl]hydrazin-1-ylidene)-2,3-dihydro-1H-indol-2-one scaffold. These compounds are active towards both RT-associated functions, DNA polymerase and ribonuclease H. The structure, biological activity and mode of action of the new derivatives have been investigated. In particular, the nature of the aromatic group in the position 4 of the thiazole ring plays a key role in the modulation of the activity towards the two RT-associated functions.

  17. 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.

  18. 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.

  19. 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.

  20. Friend of GATA-1 Represses GATA-3–dependent Activity in CD4+ T Cells

    PubMed Central

    Zhou, Meixia; Ouyang, Wenjun; Gong, Qian; Katz, Samuel G.; White, J. Michael; Orkin, Stuart H.; Murphy, Kenneth M.

    2001-01-01

    The development of naive CD4+ T cells into a T helper (Th) 2 subset capable of producing interleukin (IL)-4, IL-5, and IL-13 involves a signal transducer and activator of transcription (Stat)6-dependent induction of GATA-3 expression, followed by Stat6-independent GATA-3 autoactivation. The friend of GATA (FOG)-1 protein regulates GATA transcription factor activity in several stages of hematopoietic development including erythrocyte and megakaryocyte differentiation, but whether FOG-1 regulates GATA-3 in T cells is uncertain. We show that FOG-1 can repress GATA-3–dependent activation of the IL-5 promoter in T cells. Also, FOG-1 overexpression during primary activation of naive T cells inhibited Th2 development in CD4+ T cells. FOG-1 fully repressed GATA-3–dependent Th2 development and GATA-3 autoactivation, but not Stat6-dependent induction of GATA-3. FOG-1 overexpression repressed development of Th2 cells from naive T cells, but did not reverse the phenotype of fully committed Th2 cells. Thus, FOG-1 may be one factor capable of regulating the Th2 development. PMID:11714753

  1. 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.

  2. Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by inducible and constitutive cytochrome P450 enzymes in rats.

    PubMed

    Guo, Z; Smith, T J; Thomas, P E; Yang, C S

    1992-10-01

    The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces tumor formation in the liver, lung, nasal cavity, and pancreas of rats. Metabolic activation is required for the tumorigenicity of this compound. The involvement of cytochrome P450 enzymes in NNK bioactivation was investigated in rats by studies with chemical inducers and antibodies against P450s. Liver microsomal enzymes catalyzed the formation of 4-oxo-1-(3-pyridyl)-1-butanone (keto aldehyde), 4-hydroxy-1-(3-pyridyl)-1-butanone (keto alcohol), 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone (NNK-N-oxide), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) from NNK. When the activity was expressed on a per nanomole P450 basis, treatments of rats with 3-methylcholanthrene (MC), phenobarbital (PB), pregnenolone 16-alpha-carbonitrile (PCN), Aroclor 1254 (AR), safrole (SA), and isosafrole (ISA) increased the keto aldehyde formation in liver microsomes 2.0-, 2.4-, 3.8-, 2.5-, 2.1-, and 1.8-fold, respectively; PB, AR, SA, and ISA increased the keto alcohol formation 1.7-, 1.3-, 2.0-, and 1.3-fold, respectively. The extents of induction were more pronounced when expressed on a per milligram protein basis, due to the higher microsomal P450 contents in the induced microsomes. The formation of NNK-N-oxide was markedly increased by PB and PCN and slightly increased by AR, SA, and ISA. However, the formation of NNAL, the major metabolite due to carbonyl reduction, was not increased by the treatments but was decreased by AR, ISA, and acetone (AC). The kinetic parameters of NNK metabolism by control, MC-, PB-, and PCN-induced liver microsomes were obtained. A panel of monoclonal (anti-1A1, -2B1, -2C11, and -2E1) and polyclonal (anti-1A2, -2A1, and -3A) antibodies were used to assess the involvement of constitutive hepatic P450 enzymes in NNK metabolism. Keto aldehyde formation was inhibited by anti-1A2 and anti-3A (about 15%) but not by others; the formation of keto

  3. 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.

  4. Crystal structure and spectroscopic study on photochromism of 1,3-diphenyl-4-(4‧-fluoro)benzal-5-pyrazolone N(4)-phenyl semicarba-zone

    NASA Astrophysics Data System (ADS)

    Chai, Hui; Liu, Guangfei; Liu, Lang; Jia, Dianzeng; Guo, Zaiping; Lang, Jianping

    2005-10-01

    A novel compound 1,3-diphenyl-4-(4'-fluoro)benzal-5-pyrazolone N(4)-phenyl semicarbazone (DP4FBP-PSC) has been synthesized. X-ray single crystal structure analysis shows that the compound has interlaced structure linked by intermolecular hydrogen bonds. The results of fluorescence emission spectroscopy, UV-Vis reflection spectroscopy and the reaction rate constant indicate that DP4FBP-PSC is photochromic material. Its photochromic mechanism was investigated by structure analysis.

  5. 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.

  6. New potent inhibitors of tyrosinase: novel clues to binding of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxadiazole-2(3H)-thiones, 4-amino-1,2,4-triazole-5(4H)-thiones, and substituted hydrazides to the dicopper active site.

    PubMed

    Ghani, Usman; Ullah, Nisar

    2010-06-01

    A series of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxadiazole-2(3H)-thiones, 4-amino-1,2,4-triazole-5(4H)-thiones, and substituted hydrazides were tailored and synthesized as new potent inhibitors of tyrosinase. The rationale for inhibitor design was based on the active site structural evidence from the crystal structures of bacterial tyrosinase and potato catechol oxidase enzymes. Kinetic and active site binding studies suggested mono-dentate binding of thiadiazole, oxadiazole, and triazole rings to the active site dicopper center of tyrosinase including hydrophobicity contributing to the potent inhibition. Kinetic plots showed mixed-type of inhibition by all 25 compounds. Substitutions at C3 of the triazole ring and C5 of the thiadiazole/oxadiazole rings were found to be playing a major role in the high binding affinity to tyrosinase. The current work may help develop new potent tyrosinase inhibitors against hyperpigmentation including potential insecticides. PMID:20452224

  7. 4-Hydroxyderricin, as a PPARγ Agonist, Promotes Adipogenesis, Adiponectin Secretion, and Glucose Uptake in 3T3-L1 Cells.

    PubMed

    Li, Yongjia; Goto, Tsuyoshi; Yamakuni, Kanae; Takahashi, Haruya; Takahashi, Nobuyuki; Jheng, Huei-Fen; Nomura, Wataru; Taniguchi, Masahiko; Baba, Kimiye; Murakami, Shigeru; Kawada, Teruo

    2016-07-01

    Adipocyte differentiation plays a pivotal role in maintaining the production of small-size adipocytes with insulin sensitivity, and impaired adipogenesis is implicated in insulin resistance. 4-Hydroxyderricin (4-HD), a phytochemical component of Angelica keiskei, possesses diverse biological properties such as anti-inflammatory, antidiabetic, and antitumor. In the present study, we investigated the effects of 4-HD on adipocyte differentiation. 4-HD promoted lipid accumulation in 3T3-L1 cells, upregulated both peroxisome proliferator-activated receptor (PPAR)-γ mRNA and protein expression, and acted as a ligand for PPARγ in the luciferase assay. Moreover, 4-HD increased the mRNA and protein expression levels of adiponectin. Additionally, it promoted insulin-dependent glucose uptake into 3T3-L1 adipocytes and increased Akt phosphorylation and glucose transporter (GLUT) 4 mRNA expression. In summary, these findings suggest that 4-HD, which promoted adipogenesis and insulin sensitivity in 3T3-L1 cells, might be a phytochemical with potent insulin-sensitizing effects. PMID:27098252

  8. 3-(4-Methyl­phen­yl)-4-[(thio­semi­carba­zono)meth­yl]-1,2,3-oxa­diazol-3-ium-5-olate 1,4-dioxane hemisolvate

    PubMed Central

    Abdul Rahiman, M.; Ravikumar, G. N.; Loh, Wan-Sin; Razak, Ibrahim Abdul

    2013-01-01

    The asymmetric unit of the title compound, C11H11N5O2S·0.5C4H8O2, contains one 3-(p-tol­yl)sydnone 4-thio­semi­carba­zone mol­ecule and a half mol­ecule of 1,4-dioxane, which lies abount an inversion centre. The sydnone ring is almost planar, with a maximum deviation of 0.002 (1) Å, and forms a dihedral angle of 46.31 (5)° with the benzene ring. In the crystal, the two components are linked into a tape along [01-1] by N—H⋯O and N—H⋯S hydrogen bonds. The crystal structure is further stabilized by C—H⋯O and C—H⋯π inter­actions, forming a three-dimensional network. PMID:23723879

  9. 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...

  10. 5-(4-Chloro­phen­yl)-1-methyl-3-phenyl-3,6,8,9-tetra­hydro­pyrazolo­[3,4-b]thio­pyrano[4,3-d]pyridine

    PubMed Central

    Jia, Runhong; Peng, Juhua

    2011-01-01

    The title compound, C22H18ClN3S, was synthesized by the reaction of 4-chloro­benzaldehyde, tetra­hydro­thio­pyran-4-one and 3-methyl-1-phenyl-1H-pyrazol-5-amine in acetic acid without a catalyst. The pyridine and pyrazole rings are almost coplanar, the dihedral angle between their mean planes being 2.50 (1)°. The thio­pyran ring exhibits an envelope conformation. The crystal packing is stabilized by inter­molecular C—H⋯Cl hydrogen bonds and by C—H⋯π and π–π inter­actions [centroid–centroid distances of 3.825 (2) Å between pyridine rings and 3.557 (2) Å between pyrazole and pyridine rings. PMID:22059005

  11. Synthesis and crystal structure of a copper complex with ( E)-2-(4-(1 H-1,2,4-triazol-1-yl)benzylidene)-3,4-dihydronaphthalen-1(2 H)-one ligand

    NASA Astrophysics Data System (ADS)

    Sun, Shu-Wen; Zhang, Xiao; Wang, Gao-Feng

    2015-12-01

    The title compound, C35H23CuF6N3O5S2 ( 1), was synthesized by the reaction of Cu( tta)2 and L 1, ( L 1 = ( E)-2-(4-(1 H-1,2,4-triazol-1-yl)benzylidene)-3,4-dihydronaphthalen-1(2 H)-one) in the dichloromethane solution. It crystallizes in the monoclinic, space group P21/ c with a = 33.8388(5), b = 9.3874(2), c = 21.8194(4) Å, β = 95.522(2), V = 6898.9(2) Å3, Z = 8, D x = 1.554 Mg/m3, F(000) = 3272, µ = 0.834 mm-1, R 1 = 0.0639, wR 2 = 0.1637. The copper(II) ion of 1 is in a distorted square-pyramidal environment with four O atoms of the two tta ligands and one N atom of triazole ligand L 1. Single-crystal X-ray diffraction data revealed that the hydrogen bonds, weak C-H···π and π···π interactions in the crystals link the coordination units to form 3D supramolecular structures.

  12. Synthesis and spectral characterization of bis(4-amino-5-mercapto-1,2,4-triazol-3-yl)propane

    NASA Astrophysics Data System (ADS)

    Subashchandrabose, S.; Thanikachalam, V.; Manikandan, G.; Saleem, H.; Erdogdu, Y.

    2016-03-01

    Bis(4-amino-5-mercapto-1,2,4-triazol-3-yl)propane (BAMTP) was synthesized and characterized by FT-IR and FT-Raman spectra. Gas phase structure of BAMTP was examined under density functional theory B3LYP/6-311 ++G(d, p) level of basis set, wherein the molecule was subjected to conformational analysis. Thus the identified stable structure utilized for the calculations such as geometry optimization, vibrational behavior, hyperpolarizability analysis, natural bond orbital analysis, band gap, chemical hard/softness and stability. Geometry of BAMTP has been discussed elaborately with related crystal data. The results found from experimental and theoretical methods were reported herewith.

  13. 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; Bunin, Deborah I.; Byrge, Patricia; Iyer, Lalitha V.; Chang, Polly Y.; Abergel, Rebecca J.

    2015-02-27

    We report that the hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 minutes, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) ismore » unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of co-administered drugs metabolized by these enzymes. Plasma protein binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bi-directional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies.« less

  14. 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.

  15. 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

  16. 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.

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

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Man tests 1, 2, 3, and 4; requirements. 84.100 Section 84.100 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self-Contained Breathing Apparatus § 84.100 Man tests...

  19. 42 CFR 84.100 - Man tests 1, 2, 3, and 4; requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Man tests 1, 2, 3, and 4; requirements. 84.100 Section 84.100 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self-Contained Breathing Apparatus § 84.100 Man tests...

  20. 42 CFR 84.100 - Man tests 1, 2, 3, and 4; requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Man tests 1, 2, 3, and 4; requirements. 84.100 Section 84.100 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self-Contained Breathing Apparatus § 84.100 Man tests...

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Man tests 1, 2, 3, and 4; requirements. 84.100 Section 84.100 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self-Contained Breathing Apparatus § 84.100 Man tests...

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

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Man tests 1, 2, 3, and 4; requirements. 84.100 Section 84.100 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self-Contained Breathing Apparatus § 84.100 Man tests...

  3. Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors

    PubMed Central

    Zhang, Ling; Song, Yunlong; Huang, Jingjing; Liu, Jia; Zhu, Wenwen; Zhou, Youjun; Lv, Jiaguo; Zheng, Canhui; Zhu, Ju

    2015-01-01

    A series of 1,4-disubstituted-3,4-dihydroisoquinoline derivatives designed as tubulin polymerization inhibitors were synthesized. Their cytotoxic activities against the CEM leukemia cell line were evaluated. Most of them displayed moderate cytotoxic activities, and compounds 21 and 32 showed good activities with IC50 of 4.10 and 0.64 μM, respectively. The most potent compound 32 was further confirmed to be able to inhibit tubulin polymerization, and its hypothetical binding mode with tubulin was obtained by molecular docking. PMID:25950763

  4. Crystal structure of the 1:1 adduct of 2,3-diphenyl-3,4,5,6-tetra-hydro-2H-1,3-thia-zin-4-one with tri-phenyl-tin chloride.

    PubMed

    Yennawar, Hemant P; Fox, Ryan; Silverberg, Lee J

    2016-03-01

    The title adduct, chlorido-(2,3-diphenyl-3,4,5,6-tetra-hydro-2H-1,3-thia-zin-4-one-κO)tri-phenyl-tin, [Sn(C6H5)3Cl(C16H15NOS)], resulted from reaction of 2,3-diphenyl-3,4,5,6-tetra-hydro-2H-1,3-thia-zin-4-one with tri-phenyl-tin chloride. The thia-zine ring has an envelope conformation with the S atom forming the flap. The mol-ecule has five phenyl rings, two of them attached to the thia-zine ring at positions 2 and 3, and three in coordination with the Sn(IV) atom. The three rings of the tri-phenyl-tin group are involved in intra-molecular inter-actions of different types, C-H⋯O, edge-to-face (or T-type) π-π inter-actions with the 3-phenyl ring of the thia-zine, T-type inter-actions with both phenyl rings of the thia-zine etc. On the other hand, all the phenyl rings participate in inter-molecular π-π inter-actions. There is one instance of a 'parallel-displaced'-type inter-action extending continuously along the a-axis direction and seven instances of T-type inter-actions stabilizing the crystal lattice.

  5. 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

  6. Cationic motions and phase transitions in [(CH 3) 4N] 2SO 4·4H 2O, [(CH 3) 4N] 2SO 4, and [(CH 3) 4N] 2SeO 4 as studied by 1H NMR, differential thermal analysis, and X-ray powder diffraction techniques

    NASA Astrophysics Data System (ADS)

    Sato, Setsuko; Endo, Midori; Hara, Naoki; Nakamura, Daiyu; Ikeda, Ryuichi

    1995-02-01

    Cationic reorientations have been studied in solid [(CH 3) 4N] 2SO 4·4H 2O, [(CH 3) 4N] 2SO 4, and [(CH 3) 4N] 2SeO 4 by measuring 1H NMR spin-lattice relaxation times, T1. These motions have been discussed in association with the crystal structures and the phase transitions examined by X-ray powder diffraction and differential thermal analysis, respectively. In crystals of [(CH 3) 4N] 2SO 4·4H 2O, there are two kinds of cations distorted from regular tetrahedra. T1 is calculated according to the interpretation that two T1 minima are due to the two inequivalent (NH 3) 4N + ions reorienting at different frequencies. The result shows that at the phase transition temperatures, the correlation times to those cationic reorientations are very different from each other in this compound in contrast with (NH 4) 2SO 4 and [(CH 3) 4N] 2CdX 4 (X = Cl and Br). For the sulfate and selenate, there is a single kind of cation which can be considered tetrahedral, and the phase transitions occur in the temperature region where the narrowing of the resonance line owing to the overall cationic reorientations starts.

  7. [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

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

    SciTech Connect

    Sheu, C.W.; Moreland, F.M.; Lee, J.K.; Dunkel, V.C.

    1988-01-01

    The spermicidal surfactant nonoxynol-9 (Igepal CO-630, GAF Corp.) and a potential impurity, 1,4-dioxane, were tested in the in vitro cell transformation assay using BALB/3T3 cells. Two treatment periods, 48 hr and 13 days, were used. Nonoxynol-9, tested at levels up to 10 /sup +/g/ml, did not induce transformation, whereas dioxane was very active in the induction type II foci in the cultured BALB/3T3 cells.

  9. Synthesis, antimicrobial, and anti-inflammatory activities of novel 5-(1-adamantyl)-4-arylideneamino-3-mercapto-1,2,4-triazoles and related derivatives.

    PubMed

    Al-Omar, Mohamed A; Al-Abdullah, Ebtehal S; Shehata, Ihsan A; Habib, Elsayed E; Ibrahim, Tarek M; El-Emam, Ali A

    2010-04-01

    The reaction of 5-(1-adamantyl)-4-amino-3-mercapto-1,2,4-triazole (5) with various aromatic aldehydes in ethanol or acetic acid yielded the corresponding 4-arylideneamino derivatives 6a-v. Treatment of the 4-(2,6-difluoro- and dichlorobenzylideneamino) derivatives 6o and 6q with 1-substituted piperazines, and formaldehyde solution in ethanol afforded good yields of the corresponding 5-(1-adamantyl)-4-(2,6-dihalobenzylideneamino-2-(4-substituted-1-piperazinylmethyl)-1,2,4-triazoline-3-thiones 7a-p. 5-(1-Adamantyl)-4-arylideneamino-2-(4-ethoxycarbonyl-1-piperidylmethyl)-1,2,4-triazoline-3-thiones 8a-n, were similarly prepared via the reaction of the corresponding arylideneamino derivative with ethyl 4-piperidinecarboxylate and formaldehyde solution in ethanol. Compounds 6a-v, 7a-p and 8a-n were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Several derivatives showed good or moderate activities, particularly against the tested Gram-positive bacteria. In addition, the in vivo anti-inflammatory activity of 21 compounds was determined using the carrageenan-induced paw oedema method in rats. Compounds 7d, 7g, 7i, 7j, 7l, 8c, 8e and 8l showed good or moderate dose-dependent activity in this area. PMID:20428062

  10. Crystal structure of 4-(4-meth-oxy-phen-yl)-4',4'-dimethyl-3-p-tolyl-3',4'-di-hydro-1'H,3H-spiro-[isoxazole-5,2'-naphthalen]-1'-one.

    PubMed

    Akhazzane, Mohamed; Al Houari, Ghali; El Yazidi, Mohamed; Saadi, Mohamed; El Ammari, Lahcen

    2015-12-01

    In the title compound, C28H27NO3, the cyclo-hexa-none and isoxazole rings have envelope conformations, with the methyl-ene and spiro C atoms as the flaps, respectively. The mean plane of the isoxazole ring is inclined slightly to the p-tolyl ring, making a dihedral angle of 14.20 (9)°, and is nearly perpendicular to the mean plane through the tetra-lone moiety and to the meth-oxy-phenyl ring [dihedral angles = 83.41 (8) and 72.12 (9)°, respectively]. The crystal packing is stabilized mainly by van der Waals forces. PMID:26870562

  11. Association of galectin-1 and galectin-3 with Gemin4 in complexes containing the SMN protein.

    PubMed

    Park, J W; Voss, P G; Grabski, S; Wang, J L; Patterson, R J

    2001-09-01

    In previous studies we showed that galectin-1 and galectin-3 are factors required for the splicing of pre-mRNA, as assayed in a cell-free system. Using a yeast two-hybrid screen with galectin-1 as bait, Gemin4 was identified as a putative interacting protein. Gemin4 is one component of a macromolecular complex containing approximately 15 polypeptides, including SMN (survival of motor neuron) protein. Rabbit anti-galectin-1 co-immunoprecipitated from HeLa cell nuclear extracts, along with galectin-1, polypeptides identified to be in this complex: SMN, Gemin2 and the Sm polypeptides of snRNPs. Direct interaction between Gemin4 and galectin-1 was demonstrated in glutathione S-transferase (GST) pull-down assays. We also found that galectin-3 interacted with Gemin4 and that it constituted one component of the complex co-immunoprecipitated with galectin-1. Indeed, fragments of either Gemin4 or galectin-3 exhibited a dominant negative effect when added to a cell-free splicing assay. For example, a dose-dependent inhibition of splicing was observed in the presence of exogenously added N-terminal domain of galectin-3 polypeptide. In contrast, parallel addition of either the intact galectin-3 polypeptide or the C-terminal domain failed to yield the same effect. Using native gel electrophoresis to detect complexes formed by the splicing extract, we found that with addition of the N-terminal domain the predominant portion of the radiolabeled pre-mRNA was arrested at a position corresponding to the H-complex. Inasmuch as SMN-containing complexes have been implicated in the delivery of snRNPs to the H-complex, these results provide strong evidence that galectin-1 and galectin-3, by interacting with Gemin4, play a role in spliceosome assembly in vivo. PMID:11522829

  12. Synthesis, molecular structure, and catalytic potential of the tetrairon complex [Fe4(N3O2-L)4(mu-O)2]4+ (L = 1-carboxymethyl-4,7-dimethyl-1,4,7-triazacyclononane).

    PubMed

    Romakh, Vladimir B; Therrien, Bruno; Süss-Fink, Georg; Shul'pin, Georgiy B

    2007-04-16

    The reaction of iron sulfate with 1-carboxymethyl-4,7-dimethyl-1,4,7-triazacyclononane (L) and hydrogen peroxide in aqueous ethanol gives a brown dinuclear complex considered to be [Fe2(N3O-L)2(mu-O)(mu-OOCCH3)] + (1), which converts upon standing in acetonitrile solution into the green tetranuclear complex [Fe4(N3O2-L)4(mu-O)2]4+ (2). A single-crystal X-ray structure analysis of [2][PF6]4.5MeCN reveals 2 to contain four iron(III) centers, each of which is coordinated to three nitrogen atoms of a triazacyclononane ligand and is bridged by one oxo and two carboxylato bridges, a structural feature known from the active center of methane monooxygenase. Accordingly, complex 2 was found to catalyze the oxidative functionalization of methane with hydrogen peroxide in aqueous solution to give methanol, methyl hydroperoxide, and formic acid; the total turnover numbers attain 24 catalytic cycles within 4 h. To gain more insight into the catalytic process, the catalytic potential of 2 was also studied for the oxidation of higher alkanes, cycloalkanes, and isopropanol in acetonitrile, as well as in aqueous solution. The bond selectivities of the oxidation of linear and branched alkanes suggest a ferroxy radical pathway.

  13. Quantitative analysis of C4Ab and C4Bb binding to the C3b/C4b receptor (CR1, CD35)

    PubMed Central

    REILLY, B D; MOLD, C

    1997-01-01

    Complement-dependent clearance of immune complexes in humans is dependent on the activation and binding of the early components of the classical complement cascade. This prevents immune complex precipitation and promotes binding of the complexes by the C4b/C3b complement receptor CR1 (CD35) found on erythrocytes. The fourth component of human complement is encoded by two closely linked genes within the MHC. These genes give rise to the isotypic forms C4A and C4B, and recent studies suggest that CR1 binds activated C4A (C4Ab) to a greater extent than activated C4B (C4Bb). To study this difference in a more quantitative way the binding reactions between CR1 and C4Ab- and C4Bb-coated immune complexes and between CR1 and soluble dimers of C4Ab (C4Ab2) and C4Bb (C4Bb2) were analysed using the native receptor on human erythrocytes. The binding reaction between immune complexes with equivalent amounts of covalently bound C4Ab or C4Bb and erythrocyte CR1 showed a two-fold higher binding of complexes coated with C4A. Furthermore, erythrocyte CR1 bound C4Ab2 with an apparent four-fold higher affinity (Kd ≍ 1.4 10−7M) than C4Bb2 (Kd ≍ 4–8 10−7M), indicating a preferential binding of CR1 for C4A. PMID:9367418

  14. Synthesis and anti-inflammatory activity of some 3-(4,6-disubtituted-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl) propanoic acid derivatives.

    PubMed

    Mokale, Santosh N; Shinde, Sandeep S; Elgire, Rupali D; Sangshetti, Jaiprakash N; Shinde, Devanand B

    2010-08-01

    A series of 3-(4,6-disubtituted-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl) propanoic acid derivatives has been synthesized by condensation of thiourea, 5-(4-subtituted phenyl)-5-oxopentanoic acid and substituted aldehyde. The synthesized compounds were screened for their anti-inflammatory activity using rat paw edema method. Most of the compounds from the series showed significant (p <0.05) anti-inflammatory activity.

  15. The Synthesis of 1-Phenyl-1,2,3,4-tetrahydroisoquinolines: An Undergraduate Organic Laboratory Experiment and Class Project.

    ERIC Educational Resources Information Center

    Letcher, R. M.; Sammes, M. P.

    1985-01-01

    Describes an undergraduate organic chemistry experiment (requiring three/four 3-hour laboratory sessions) involving a four-stage synthesis of 1-phenyl-1,2,3,4-tetrahydroisoquinolines via the Pictet-Spengler route. In addition, the experiment allows students to study the spectra and properties of aklaloid-like materials while completing several…

  16. Characteristics of nitrogen release from synthetic zeolite Na-P1 occluding NH4NO3.

    PubMed

    Park, Man; Kim, Jong Su; Choi, Choong Lyeal; Kim, Jang-Eok; Heo, Nam Ho; Komarneni, Sridhar; Choi, Jyung

    2005-08-18

    Zeolites can accommodate a considerable amount of occluded salt such as NH4NO3, which can serve as a good source of slow-release plant nutrient. This study evaluates the kinetics of ion release from NH4NO3-occluded Na-P1 (N-NaP) using a simulated soil solution and deionized water as leaching solutions. The patterns of ion releases were examined as a function of leaching time under both static and continuous-flow conditions for more than one month. Releases of both NH4+ and NO3- from N-NaP were found to be slow and steady under both the above conditions. The soil solution affected the release of NH4+ and NO3- differently, while deionized water released nearly the same equivalents of these ions. This clearly indicates that ion release from salt-occluded zeolite involves two different reactions, cation exchange and dissolution. The kinetics of ion release from occluded NH4NO3 under static condition was best described by the standard Elovich model while the power function model best expressed these under continuous-flow condition. The initial ion release patterns under both conditions exhibited considerable deviation from the simulated models, probably as a result of the presence of hydrated occluded NH4NO3. Flow condition and the presence of electrolytes in leaching solution affected the release kinetics significantly. Release of occluded NH4NO3 was delayed by the presence of the NH4NO3 coated on zeolite crystals. These results indicate that the ion release property of occluded salt could be predicted and controlled. This study clearly shows that NH4NO3-occluded zeolites could be developed as slow release fertilizers. PMID:15963593

  17. 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.

  18. The conformational energies of 2-methyl- and 4-methyl-1,3-dithiane. The breakdown of 1,3- syn diaxial repulsion hypothesis

    NASA Astrophysics Data System (ADS)

    Ribeiro, Douglas S.; Rittner, Roberto

    2003-09-01

    The conformational enthalpies (Δ H) of 2-methyl- (-1.76 kcal mol -1) and 4-methyl-1,3-dithiane (-1.75 kcal mol -1) were obtained by the analysis of 13C chemical shifts as a function of temperature. These energies are in excellent agreement both with calculated values (B3LYP/6-31G(d,p)) and with literature values based on 2,4-dialkyl-1,3-dithiane. The results confirm the similarity between the conformational energies of the methyl group at the 2 and 4 positions of the dithiane ring and that of methylcyclohexane, despite the larger distances between ring 1,3- syn- axial hydrogens and the closest methyl axial hydrogen in the dithiane ring. The possibility of a buttressing effect on the 2,4-dialkyl-1,3-dithianes previously studied and the rationale of 1,3- syn-axial steric interaction are discussed.

  19. (E)-1-(3-Bromo­phen­yl)-3-(3,4-dimeth­oxy­phen­yl)prop-2-en-1-one

    PubMed Central

    Escobar, Carlos A.; Trujillo, Alexander; Howard, Judith A. K.; Fuentealba, Mauricio

    2012-01-01

    The mol­ecular structure of the title compound, C17H15BrO3, consists of a bromo­phenyl and a 3,4-dimeth­oxy­phenyl group linked through a prop-2-en-1-one spacer. The C=C double bond displays an E conformation, while the carbonyl group shows an S-cis conformation relative to the double bond. PMID:22412737

  20. The reaction of 4,5-dichloro-1,2,3-dithiazolium chloride with sulfimides: a new synthesis of N-aryl-1,2,3-dithiazolimines.

    PubMed

    Kalogirou, Andreas S; Koutentis, Panayiotis A

    2009-01-01

    N-Aryl-S,S-dimethylsulfimides 3(Ar = 4-NO(2)C(6)H(4)), 4 (Ar = Ph) and 5 (Ar = 4-Tol)react with Appel salt 1 to give the corresponding N-aryl-(4-chloro-5H-1,2,3-dithiazolylidene)benzenamines 8 (Ar = 4-NO(2)C(6)H(4)), 9 (Ar = Ph) and 10 (Ar = 4-Tol) in 84, 94 and 87% yields, respectively. The reaction proceeds in the absence of base and a proposed reaction mechanism is given. PMID:19633609

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

    PubMed

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

    2016-07-01

    PTEN is a lipid phosphatase that converts phosphatidylinositol 3,4,5-phosphate (PIP3) to phosphatidylinositol 4,5-phosphate (PIP2) and plays a critical role in the regulation of tumor growth. PTEN is subject to regulation by a variety of post-translational modifications, including phosphorylation on a C-terminal cluster of four Ser/Thr residues (380, 382, 383, and 385) and ubiquitylation by various E3 ligases, including NEDD4-1 and WWP2. It has previously been shown that C-terminal phosphorylation of PTEN can increase its cellular half-life. Using in vitro ubiquitin transfer assays, we show that WWP2 is more active than NEDD4-1 in ubiquitylating unphosphorylated PTEN. The mapping of ubiquitylation sites in PTEN by mass spectrometry showed that both NEDD4-1 and WWP2 can target a broad range of Lys residues in PTEN, although NEDD4-1 versus WWP2 showed a stronger preference for ubiquitylating PTEN's C2 domain. Whereas tetraphosphorylation of PTEN did not significantly affect its ubiquitylation by NEDD4-1, it inhibited PTEN ubiquitylation by WWP2. Single-turnover and pull-down experiments suggested that tetraphosphorylation of PTEN appears to weaken its interaction with WWP2. These studies reveal how the PTEN E3 ligases WWP2 and NEDD4-1 exhibit distinctive properties in Lys selectivity and sensitivity to PTEN phosphorylation. Our findings also provide a molecular mechanism for the connection between PTEN Ser/Thr phosphorylation and PTEN's cellular stability.

  2. Properties of a thermoactive beta-1,3-1,4-glucanase (lichenase) from Clostridium thermocellum expressed in Escherichia coli.

    PubMed

    Schimming, S; Schwarz, W H; Staudenbauer, W L

    1991-05-31

    A Clostridium thermocellum gene (licB) encoding a thermoactive 1,3-1,4-beta-glucanase (lichenase) with a molecular weight of about 35,000 was localized on a 1.5-kb DNA fragment by cloning and expression in E. coli. The enzyme acts on beta-glucans with alternating beta-1,3- and beta-1,4-linkages such as barley beta-glucan and lichenan, but not on beta-glucans containing only 1,3- or 1,4-glucosidic bonds. It is active over a broad pH range (pH 5-12) and has a temperature optimum around 80 degrees C. The C. thermocellum lichenase is unusually resistant against inactivation by heat, ethanol or ionic detergents. These properties make the enzyme highly suitable for industrial application in the mashing process of beer brewing.

  3. NAD+-SIRT1 control of H3K4 trimethylation through circadian deacetylation of MLL1

    PubMed Central

    Aguilar-Arnal, Lorena; Katada, Sayako; Orozco-Solis, Ricardo

    2015-01-01

    The circadian clock controls the transcription of hundred genes through specific chromatin remodeling events. The histone methyltransferase Mixed-Lineage Leukemia 1 (MLL1) coordinates recruitment of CLOCK–BMAL1 activator complexes to chromatin, an event associated to cyclic H3K4 tri-methylation at circadian promoters. Remarkably, in mouse liver circadian H3K4me3 is modulated by SIRT1, a NAD+ dependent deacetylase involved in clock control. We show that mammalian MLL1 is acetylated at two conserved residues, K1130 and K1133. Notably, MLL1 acetylation is cyclic, controlled by the clock and by SIRT1, and impacts the methyltransferase activity of MLL1. Moreover, H3K4 methylation at clock-controlled gene promoters is influenced by pharmacological or genetic inactivation of SIRT1. Finally, MLL1 acetylation and H3K4me3 levels at circadian gene promoters depend on NAD+ circadian levels. These findings reveal a previously unappreciated regulatory pathway between energy metabolism and histone methylation. PMID:25751424

  4. Vibrational signatures of hydrogen bonding in the protonated ammonia clusters NH4+(NH3)1-4

    NASA Astrophysics Data System (ADS)

    Yang, Y.; Kühn, O.; Santambrogio, G.; Goebbert, D. J.; Asmis, K. R.

    2008-12-01

    The gas phase vibrational spectroscopy of the protonated ammonia dimer N2H7+, a prototypical system for strong hydrogen bonding, is studied in the spectral region from 330 to 1650 cm-1 by combining infrared multiple photon dissociation and multidimensional quantum mechanical simulations. The fundamental transition of the antisymmetric proton stretching vibration is observed at 374 cm-1 and assigned on the basis of a six-dimensional model Hamiltonian, which predicts this transition at 471 cm-1. Photodissociation spectra of the larger protonated ammonia clusters NH4+(NH3)n with n =2-4 are also reported for the range from 1050 to 1575 cm-1. The main absorption features can be assigned within the harmonic approximation, supporting earlier evidence that hydrogen bonding in these clusters is considerably weaker than for n =1.

  5. Scandium-catalyzed tandem selective oxirane ring-opening/Friedel-Crafts alkylation: a facile access to [1,4]oxazino[4,3-a]indoles and 3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazines.

    PubMed

    Wei, Lai; Liu, Lu; Zhang, Junliang

    2014-09-21

    A facile technique involving a novel Lewis-acid-catalyzed tandem selective ring-opening of oxirane and Friedel-Crafts alkylation of 1H-indol-1-yl derived oxiranes was developed. The developed protocol affords functionalized [1,4]oxazino[4,3-a]indoles and 3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazines in up to 95% yield.

  6. Scandium-catalyzed tandem selective oxirane ring-opening/Friedel-Crafts alkylation: a facile access to [1,4]oxazino[4,3-a]indoles and 3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazines.

    PubMed

    Wei, Lai; Liu, Lu; Zhang, Junliang

    2014-09-21

    A facile technique involving a novel Lewis-acid-catalyzed tandem selective ring-opening of oxirane and Friedel-Crafts alkylation of 1H-indol-1-yl derived oxiranes was developed. The developed protocol affords functionalized [1,4]oxazino[4,3-a]indoles and 3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazines in up to 95% yield. PMID:25053291

  7. Nitrogen bridgehead compounds. 38. New antiallergic 4H-pyrido[1,2-a]pyrimidin-4-ones. 3.

    PubMed

    Hermecz, I; Breining, T; Vasvári-Debreczy, L; Horváth, A; Mészáros, Z; Bitter, I; DeVos, C; Rodriguez, L

    1983-10-01

    The weak antiallergic activity of 6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid (4) on the rat reaginic passive cutaneous anaphylaxis test was enhanced by the introduction of appropriate functional groups into position 9 of the pyridopyrimidine ring. The most active 9-substituted pyridopyrimidinecarboxylic acids contained an oxime, a phenylamino, or a (phenylamino)thioxomethyl group in position 9. The 9-phenylcarboxamido and 9-phenylhydrazono moieties may be regarded as bioisosteric groups in the pyridopyrimidinone series. In the series of 9-(arylamino)dihydropyridopyrimidines, the structure-activity relationship study revealed similar relationships as found for the 9-(arylhydrazono)tetrahydropyridopyrimidines. The biological activity was due to the 6S enantiomers. A monosubstituted arylamino moiety in position 9 was necessary for the intravenous activity. The most active compound, 9-[(3-acetylphenyl)amino]-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H- pyrido[1,2-a]pyrimidine-3-carboxylic acid (40) was three times as active as the reference sodium chromoglycate (DSCG) in the passive cutaneous anaphylaxis (PCA) test.

  8. 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.

  9. Synthesis, antimicrobial, and anti-inflammatory activities of novel 2-[3-(1-adamantyl)-4-substituted-5-thioxo-1,2,4-triazolin-1-yl] acetic acids, 2-[3-(1-adamantyl)-4-substituted-5-thioxo-1,2,4-triazolin-1-yl]propionic acids and related derivatives.

    PubMed

    Al-Deeb, Omar A; Al-Omar, Mohamed A; El-Brollosy, Nasser R; Habib, Elsayed E; Ibrahim, Tarek M; El-Emam, Ali A

    2006-01-01

    The reaction of 3-(1-adamantyl)-4-substituted-1,2,4-triazoline-5-thiones 3a-g with sodium chloroacetate, in ethanolic sodium hydroxide yielded the corresponding N1-acetic acid derivatives 4a-g. The interaction of 3a-g with ethyl 2-bromopropionate in acetone, in the presence of potassium carbonate, yielded the corresponding N1-ethyl propionate derivatives 5a-g, which upon hydrolysis with aqueous sodium hydroxide afforded the corresponding propionic acid derivatives 6a-g. Similarly, the reaction of 3-(1-adamantyl)-4-amino-1,2,4-triazoline-5-thione 7 with sodium chloroacetate in ethanolic sodium hydroxide yielded the corresponding N1-acetic acid derivative 8. On the other hand, the reaction of 2-(1-adamantyl)-1,3,4-oxadiazoline-5-thione 9 with sodium chloroacetate yielded the corresponding S-acetic acid derivative 10. Compounds 4a-g, 5b, 5c, 5g, 6a-g, 8 and 10 were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Several derivatives produced good or moderate activities particularly against Bacillus subtilis. In addition, the in vivo anti-inflammatory activities of these compounds were determined using the carrageenin-induced paw oedema method in rats. Compounds 4a, 4b, 4e, 4f, 6f, 6g and 10 produced good dose-dependent anti-inflammatory activities. PMID:16478004

  10. 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

    2015-05-01

    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.

  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. Crystal structure of 1-benzyl-4-formyl-1H-pyrrole-3-carb-oxamide.

    PubMed

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

    2016-02-01

    In the title compound, C13H12N2O2 (I), the mean planes of the pyrrole and benzyl rings are approximately perpendicular, forming a dihedral angle of 87.07 (4) °. There is an intra-molecular N-H⋯O hydrogen bond forming an S(7) ring motif. In the crystal, mol-ecules are linked via a pair of N-H⋯O hydrogen bonds forming inversion dimers. C-H⋯O hydrogen bonds link the dimers into chains along direction [10-1]. The chains are further linked by weak C-H⋯π inter-actions forming layers parallel to the ac plane. PMID:26958371

  13. Rotational spectrum, conformation and dipole moment of 4-methyl-1,3-dioxane

    NASA Astrophysics Data System (ADS)

    Shapkin, A. A.; Galeev, R. V.; Gunderova, L. N.; Fayzullin, M. G.; Mamleev, A. H.

    2006-12-01

    The rotational spectrum of 4-methyl-1,3-dioxane, C 5H 100 II, has been recorded from 16.0 to 40.0 GHz. The a-, b- and C- type transitions with J<=57 have been observed and assigned for the normal species in the ground vibrational state. The rotational constants and the quartic centrifugal distortion constants were determined to be A = 4802.335(2) MHz, B = 2376.163(1) MHz, C = 1738.852(1) MHz and Δ J = 0.1496(6) kHz, Δ JK = 0.157(5) kHz, Δ K = 0.76(3) kHz, δJ = 0.0423(1) kHz, δK 0.260(3) kHz. Stark effect measurements were used to determine the projections of the dipole moment on the principal inertial axes (in Debye units): μ a = 0.73(1), μ b = 1.32(1), c = 1.36(1) and μ tot = 2.03(2). Comparison of the experimental rotational constants and dipole moment components with results of ab initio calculations (B3PW91/aug-cc-pVDZ) shown that 4-methyl-l,3-dioxane exist in chair form with equatorial orientation of methyl group.

  14. The E3 ubiquitin ligase Mib1 regulates Plk4 and centriole biogenesis.

    PubMed

    Čajánek, Lukas; Glatter, Timo; Nigg, Erich A

    2015-05-01

    Centrioles function as core components of centrosomes and as basal bodies for the formation of cilia and flagella. Thus, effective control of centriole numbers is essential for embryogenesis, tissue homeostasis and genome stability. In mammalian cells, the centriole duplication cycle is governed by Polo-like kinase 4 (Plk4). Here, we identify the E3 ubiquitin ligase Mind bomb (Mib1) as a new interaction partner of Plk4. We show that Mib1 localizes to centriolar satellites but redistributes to centrioles in response to conditions that induce centriole amplification. The E3 ligase activity of Mib1 triggers ubiquitylation of Plk4 on multiple sites, causing the formation of Lys11-, Lys29- and Lys48-ubiquitin linkages. These modifications control the abundance of Plk4 and its ability to interact with centrosomal proteins, thus counteracting centriole amplification induced by excess Plk4. Collectively, these results identify the interaction between Mib1 and Plk4 as a new and important element in the control of centriole homeostasis.

  15. Tunable photoluminescence properties of Sr(1-y)CayMoO4:Sm3+ phosphors (0 ≤ y < 1).

    PubMed

    Cao, Renping; Chen, Kangbin; Liu, Pan; Cao, Chunyan; Xu, Yongchun; Ao, Hui; Tang, Pengjie

    2015-11-01

    A series of Sr(1-x-y)CayMoO4:xSm(3+) (0 ≤ x ≤ 7 mol% and 0 ≤ y < 1) phosphors was synthesized by a conventional solid-state reaction method in air, and their structural and spectroscopic properties were investigated. The optimal doping concentration of Sm(3+) in SrMoO4:Sm(3+) phosphor is 5 mol%. Under excitation with 275 nm, in Sr(1-x-y)CayMoO4:xSm(3+) (0 ≤ x ≤ 7 mol% and 0 ≤ y < 1) phosphors, the emission band of the host was found to overlap with the excitation bands peaking at ~ 500 nm of Sm(3+) ion, and the energy transfer from MoO4 (2-) group to Sm(3+) ion can also be observed. The International Commission on Illumination (CIE) chromaticity coordinates of Sr(0.95-y)CayMoO4:0.05Sm(3+) phosphors with excitation 275 nm varied systematically from an orange (0.4961, 0.3761) (y = 0) to a white color (0.33, 0.3442) (y = 0.95) with increasing calcium oxide (CaO) concentration. However, Sr(0.95-y)CayMoO4:0.05Sm(3+) phosphors with excitation at 404 nm only showed red emission and the energy transfer between MoO4(2-) group to Sm(3+) ion was not observed. The complex mechanisms of luminescence and energy transfer are discussed by energy level diagrams of MoO4(2-) group and Sm(3+) ion. PMID:25645573

  16. (4S)-(−)-4-Benzyl-2,2-dimethyl-3-o-toluoyl-1,3-oxazolidine

    PubMed Central

    Gzella, Andrzej K.; Chrzanowska, Maria; Dreas, Agnieszka; Meissner, Zofia

    2010-01-01

    The absolute configuration of the title compound, C20H23NO2, has been confirmed as 4S. The benzyl residue and H atom at the asymmetric C-atom centre occupy pseudo-axial and bis­ectional positions, respectively. The oxazolidine ring adopts an envelope conformation. In the crystal structure, the mol­ecular packing is stabilized by non-classical C—H⋯O hydrogen bonds. PMID:21589035

  17. 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].

  18. Carbonic anhydrase inhibition by 1-aroyl-3-(4-aminosulfonylphenyl)thioureas.

    PubMed

    Saeed, Aamer; Al-Rashida, Mariya; Hamayoun, Mehwish; Mumtaz, Amara; Iqbal, Jamshed

    2014-12-01

    A series of 1-aroyl-3-(4-aminosulfonylphenyl)thioureas containing free sulfonamide group has been evaluated for their ability to inhibit bovine carbonic anhydrase II (bCA, EC 4.2.1.1). All compounds in the series were able to inhibit bCA II, the most active inhibitor had IC50 value of 0.26 ± 0.01 µM. Molecular docking studies and detailed structure-activity relationship studies were carried out. The absorption, distribution, metabolism, excretion (ADME) properties, as a predictor of oral absorption, were computationally calculated and compared with the clinically used drug acetazolamide. PMID:24666305

  19. Drug Discovery against Psoriasis: Identification of a New Potent FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor, 1-(4-((1H-Pyrazolo[3,4-d]pyrimidin-4-yl)oxy)-3-fluorophenyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea, That Showed Potent Activity in a Psoriatic Animal Model.

    PubMed

    Li, Guo-Bo; Ma, Shuang; Yang, Ling-Ling; Ji, Sen; Fang, Zhen; Zhang, Guo; Wang, Li-Jiao; Zhong, Jie-Min; Xiong, Yu; Wang, Jiang-Hong; Huang, Shen-Zhen; Li, Lin-Li; Xiang, Rong; Niu, Dawen; Chen, Ying-Chun; Yang, Sheng-Yong

    2016-09-22

    Psoriasis is a chronic T-cell-mediated autoimmune disease, and FMS-like tyrosine kinase 3 (FLT3) has been considered as a potential molecular target for the treatment of psoriasis. In this investigation, structural optimization was performed on a lead compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea (1), which showed a moderate inhibitory activity againt FLT3. A series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized, and structure-activity relationship analysis led to the discovery of a number of potent FLT3 inhibitors. One of the most active compounds, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-fluorophenyl)-3-(5-tert-butylisoxazol-3-yl)urea (18b), was then chosen for in-depth antipsoriasis studies because this compound displayed the highest potency in a preliminary antipsoriasis test. Compound 18b exhibited significant antipsoriatic effects in the K14-VEGF transgenic mouse model of psoriasis, and no recurrence was found 15 days later after the last administration. Detailed mechanisms of action of compound 18b were also investigated. Collectively, compound 18b could be a potential drug candidate for psoriasis treatment.

  20. Na(+)/H (+) exchanger isoform 1 induced osteopontin expression in cardiomyocytes involves NFAT3/Gata4.

    PubMed

    Mlih, Mohamed; Abdulrahman, Nabeel; Gadeau, Alain-Pierre; Mohamed, Iman A; Jaballah, Maiy; Mraiche, Fatima

    2015-06-01

    Osteopontin (OPN), a multifunctional glycophosphoprotein, has been reported to contribute to the development and progression of cardiac remodeling and hypertrophy. Cardiac-specific OPN knockout mice were protected against hypertrophy and fibrosis mediated by Ang II. Recently, transgenic mice expressing the active form of the Na(+)/H(+) exchanger isoform 1 (NHE1) developed spontaneous hypertrophy in association with elevated levels of OPN. The mechanism by which active NHE1 induces OPN expression and contributes to the hypertrophic response remains unclear. To validate whether expression of the active form of NHE1 induces OPN, cardiomyocytes were stimulated with Ang II, a known inducer of both OPN and NHE1. Ang II induced hypertrophy and increased OPN protein expression (151.6 ± 28.19 %, P < 0.01) and NHE1 activity in H9c2 cardiomyoblasts. Ang II-induced hypertrophy and OPN protein expression were regressed in the presence of an NHE1 inhibitor, EMD 87580, or a calcineurin inhibitor, FK506. In addition, our results indicated that activation of NHE1-induced NFAT3 translocation into the nucleus and a significant activation of the transcription factor Gata4 (NHE1: 149 ± 28 % of control, P < 0.05). NHE1-induced activation of Gata4 was inhibited by FK506. In summary, our results suggest that activation of NHE1 induces hypertrophy through the activation of NFAT3/Gata4 and OPN expression. PMID:25758355

  1. Organometallic 3-(1H-Benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines as Potential Anticancer Agents

    PubMed Central

    2011-01-01

    Six organometallic complexes of the general formula [MIICl(η6-p-cymene)(L)]Cl, where M = Ru (11a, 12a, 13a) or Os (11b, 12b, 13b) and L = 3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines (L1–L3) have been synthesized. The latter are known as potential cyclin-dependent kinase (Cdk) inhibitors. All compounds have been comprehensively characterized by elemental analysis, one- and two-dimensional NMR spectroscopy, UV–vis spectroscopy, ESI mass spectrometry, and X-ray crystallography (11b and 12b). The multistep synthesis of 3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines (L1–L3), which was reported by other researchers, has been modified by us essentially (e.g., the synthesis of 5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid (3) via 5-bromo-3-methyl-1H-pyrazolo[3,4-b]pyridine (2); the synthesis of 1-methoxymethyl-2,3-diaminobenzene (5) by avoiding the use of unstable 2,3-diaminobenzyl alcohol; and the activation of 1H-pyrazolo[3,4-b]pyridine-3-carboxylic acids (1, 3) through the use of an inexpensive coupling reagent, N,N′-carbonyldiimidazole (CDI)). Stabilization of the 7b tautomer of methoxymethyl-substituted L3 by coordination to a metal(II) center, as well as the NMR spectroscopic characterization of two tautomers 7b-L3 and 4b′-L3 in a metal-free state are described. Structure–activity relationships with regard to cytotoxicity and cell cycle effects in human cancer cells, as well as Cdk inhibitory activity, are also reported. PMID:22032295

  2. Upregulation of the E3 ligase NEDD4-1 by Oxidative Stress Degrades IGF-1 Receptor Protein in Neurodegeneration

    PubMed Central

    Kwak, Young-Don; Wang, Bin; Li, Jing Jing; Wang, Ruishan; Deng, Qiyue; Diao, Shiyong; Chen, Yaomin; Xu, Raymond; Masliah, Eliezer; Xu, Huaxi; Sung, Jung-Joon

    2012-01-01

    The importance of ubiquitin E3 ligases in neurodegeneration is being increasingly recognized. The crucial role of NEDD4-1 in neural development is well appreciated; however, its role in neurodegeneration remains unexplored. Herein, we report increased NEDD4-1 expression in the degenerated tissues of several major neurodegenerative diseases. Moreover, its expression is upregulated in cultured neurons in response to various neurotoxins, including zinc and hydrogen superoxide, via transcriptional activation likely mediated by the reactive oxygen species (ROS)-responsive FOXM1B. Reduced protein levels of the insulin-like growth factor receptor (IGF-1Rβ) were observed as a consequence of upregulated NEDD4-1 via the ubiquitin-proteasome system. Overexpression of a familial mutant form of superoxide dismutase 1 (SOD1) (G93A) in neuroblastoma cells resulted in a similar reduction of IGF-1Rβ protein. This inverse correlation between NEDD4-1 and IGF-1Rβ was also observed in the cortex and spinal cords of mutant (G93A) SOD1 transgenic mice at a presymptomatic age, which was similarly induced by in vivo-administered zinc in wild-type C57BL/6 mice. Furthermore, histochemistry reveals markedly increased NEDD4-1 immunoreactivity in the degenerating/degenerated motor neurons in the lumbar anterior horn of the spinal cord, suggesting a direct causative role for NEDD4-1 in neurodegeneration. Indeed, downregulation of NEDD4-1 by shRNA or overexpression of a catalytically inactive form rescued neurons from zinc-induced cell death. Similarly, neurons with a NEDD4-1 haplotype are more resistant to apoptosis, largely due to expression of higher levels of IGF-1Rβ.Together, our work identifies a novel molecular mechanism for ROS-upregulated NEDD4-1 and the subsequently reduced IGF-1Rβ signaling in neurodegeneration. PMID:22875931

  3. 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

  4. Synthesis and kinase inhibitory activity of new sulfonamide derivatives of pyrazolo[4,3-e][1,2,4]triazines.

    PubMed

    Mojzych, Mariusz; Šubertová, Veronika; Bielawska, Anna; Bielawski, Krzysztof; Bazgier, Václav; Berka, Karel; Gucký, Tomáš; Fornal, Emilia; Kryštof, Vladimír

    2014-05-01

    A new series of sulfonamide derivatives of pyrazolo[4,3-e][1,2,4]triazine has been synthesized and characterized. Their anticancer activity was tested in vitro against multiple human cancer cell lines and were found to have dose-dependent antiproliferative effects. Furthermore, some of the new compounds inhibited the Abl protein kinase with low micromolar IC50 values and exhibited selective activity against the Bcr-Abl positive K562 and BV173 cell lines, providing starting points for the further development of this new kinase inhibitor scaffold.

  5. Calorimetric and computational study of 2H-1, 4-benzoxazin-3(4H)-one and of related species

    NASA Astrophysics Data System (ADS)

    Agostinha, M.; Matos, R.; Miranda, Margarida S.; Morais, Victor M. F.; Liebman, Joel F.

    The standard molar enthalpy of formation in the gas phase of 2H-1,4-benzoxazin-3(4H)-one was derived from the standard energy of combustion determined by static bomb combustion calorimetry in oxygen atmosphere and from the standard sublimation enthalpy determined by Calvet microcalorimetry. In addition, we report the results of a systematic theoretical study of the keto and enol tautomers in benzoxazinones and diones using density functional theory. The keto tautomers are computed to be more stable than the enols. Tautomerization energies are reported.

  6. A New 1,3,4-Oxadiazole-Based Hole-Transport Material for Efficient CH3 NH3 PbBr3 Perovskite Solar Cells.

    PubMed

    Carli, Stefano; Baena, Juan Pablo Correa; Marianetti, Giulia; Marchetti, Nicola; Lessi, Marco; Abate, Antonio; Caramori, Stefano; Grätzel, Michael; Bellina, Fabio; Bignozzi, Carlo Alberto; Hagfeldt, Anders

    2016-04-01

    A new hole-transport material (HTM) based on the 1,3,4-oxadiazole moiety (H1) was prepared through a single-step synthetic pathway starting from commercially available products. Thanks to a deep HOMO level, H1 was used as HTM in CH3 NH3 PbBr3 perovskite solar cells yielding an efficiency of 5.8%. The reference HTM (Spiro-OMeTAD), under the same testing conditions, furnished a lower efficiency of 5.1%. Steady-state and time-resolved photoluminescence of the thin films showed good charge-extraction dynamics for H1 devices. In addition, H1 shows a large thermal stability and completely amorphous behavior (as evaluated by thermal gravimetric analysis and differential scanning calorimetry).

  7. (E)-2,2-Dimethyl-5-(3-phenyl-allyl-idene)-1,3-dioxane-4,6-dione.

    PubMed

    Zeng, Wu-Lan

    2010-01-01

    The title compound, C(15)H(14)O(4), was prepared by the reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione and (Z)-3-phenyl-acryl-aldehyde in ethanol. The dioxane ring is in a sofa conformation with the C atom bonded to the two methyl groups forming the flap. With the exception of the flap atom and the methyl group C atoms, all other non-H atoms are essentially planar, with an r.m.s. deviation of 0.067 (1) Å. The crystal structure is stabilized by weak inter-molecular C-H⋯O hydrogen bonds. PMID:21589113

  8. The H3K9 methyltransferase Setdb1 regulates TLR4-mediated inflammatory responses in macrophages

    PubMed Central

    Hachiya, Rumi; Shiihashi, Takuya; Shirakawa, Ibuki; Iwasaki, Yorihiro; Matsumura, Yoshihiro; Oishi, Yumiko; Nakayama, Yukiteru; Miyamoto, Yoshihiro; Manabe, Ichiro; Ochi, Kozue; Tanaka, Miyako; Goda, Nobuhito; Sakai, Juro; Suganami, Takayoshi; Ogawa, Yoshihiro

    2016-01-01

    Proinflammatory cytokine production in macrophages involves multiple regulatory mechanisms, which are affected by environmental and intrinsic stress. In particular, accumulating evidence has suggested epigenetic control of macrophage differentiation and function mainly in vitro. SET domain, bifurcated 1 (Setdb1, also known as Eset) is a histone 3 lysine 9 (H3K9)-specific methyltransferase and is essential for early development of embryos. Here we demonstrate that Setdb1 in macrophages potently suppresses Toll-like receptor 4 (TLR4)-mediated expression of proinflammatory cytokines including interleukin-6 through its methyltransferase activity. As a molecular mechanism, Setdb1-deficiency decreases the basal H3K9 methylation levels and augments TLR4-mediated NF-κB recruitment on the proximal promoter region of interleukin-6, thereby accelerating interleukin-6 promoter activity. Moreover, macrophage-specific Setdb1-knockout mice exhibit higher serum interleukin-6 concentrations in response to lipopolysaccharide challenge and are more susceptible to endotoxin shock than wildtype mice. This study provides evidence that the H3K9 methyltransferase Setdb1 is a novel epigenetic regulator of proinflammatory cytokine expression in macrophages in vitro and in vivo. Our data will shed insight into the better understanding of how the immune system reacts to a variety of conditions. PMID:27349785

  9. 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......

  10. Investigations of preferential solvation on 1,4-dimethoxy-3-methyl anthracene-9,10-dione.

    PubMed

    Umadevi, M; Kumari, M Vadana; Bharathi, M Suthandera; Vanelle, P; Terme, T

    2011-01-01

    Preferential solvation of 1,4-dimethoxy-3-methyl anthracene-9,10-dione (DMMAD) has been investigated using optical absorption technique. The preferential solvation parameters show that the DMMAD is preferentially solvated by acetone in acetone (AC)+propan-2-ol (PROH), AC+CH2Cl2 and AC+CCl4 mixtures. DMMAD prefers PROH in PROH+CCl4 mixture. In the case of benzene+CCl4 mixture DMMAD is preferentially solvated by benzene in benzene rich region and by CCl4 in CCl4 rich region. The results have been discussed in terms of hydrogen bonding, dipole-dipole and induced dipole-dipole interactions between DMMAD and solvent molecules.

  11. Characterization of an Arabidopsis inositol 1,3,4,5,6-pentakisphosphate 2-kinase (AtIPK1)

    PubMed Central

    Sweetman, Dylan; Johnson, Sue; Caddick, Samuel E. K.; Hanke, David E.; Brearley, Charles A.

    2005-01-01

    The metabolic pathway(s) by which plants synthesize InsP6 (inositol 1,2,3,4,5,6-hexakisphosphate) remains largely undefined [Shears (1998) Biochim. Biophys. Acta 1436, 49–67], while the identities of the genes that encode enzymes catalysing individual steps in these pathways are, with the notable exception of myo-inositol phosphate synthase and ZmIpk [Shi, Wang, Wu, Hazebroek, Meeley and Ertl (2003) Plant Physiol. 131, 507–515], unidentified. A yeast enzyme, ScIPK1, catalyses the synthesis of InsP6 by 2-phosphorylation of Ins(1,3,4,5,6)P5 (inositol 1,3,4,5,6-pentakisphosphate). A human orthologue, HsIPK1, is able to substitute for yeast ScIPK1, restoring InsP6 production in a Saccharomyces cerevisiae mutant strain lacking the ScIPK1 open reading frame (ScIpk1Δ). We have identified an Arabidopsis genomic sequence, AtIPK1, encoding an Ins(1,3,4,5,6)P5 2-kinase. Inclusion of the AtIPK1 protein in alignments of amino acid sequences reveals that human and Arabidopis kinases are more similar to each other than to the S. cerevisiae enzyme, and further identifies an additional motif. Recombinant AtIPK1 protein expressed in Escherichia coli catalysed the synthesis of InsP6 from Ins(1,3,4,5,6)P5. The enzyme obeyed Michaelis–Menten kinetics with an apparent Vmax of 35 nmol·min−1·(mg of protein)−1 and a Km for Ins(1,3,4,5,6)P5 of 22 μM at 0.4 mM ATP. RT (reverse transcriptase)–PCR analysis of AtIPK1 transcripts revealed that AtIPK1 is expressed in siliques, leaves and cauline leaves. In situ hybridization experiments further revealed strong expression of AtIPK1 in male and female organs of flower buds. Expression of AtIPK1 protein in an ScIpk1Δ mutant strain restored InsP6 production and rescued the temperature-sensitive growth phenotype of the yeast. PMID:16223361

  12. Diffusion of 4-methyl-pent-3-en-2-one (1); air (2)

    NASA Astrophysics Data System (ADS)

    Winkelmann, J.

    This document is part of Subvolume A `Gases in Gases, Liquids and their Mixtures' of Volume 15 `Diffusion in Gases, Liquids and Electrolytes' of Landolt-Börnstein Group IV `Physical Chemistry'. It is part of the chapter of the chapter `Diffusion in Pure Gases' and contains data on diffusion of (1) 4-methyl-pent-3-en-2-one; (2) air

  13. 1. Building C9; 3/4 view, looking SE; showing storage tanks ...

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

    1. Building C-9; 3/4 view, looking SE; showing storage tanks on the west side of the building and the railroad tracks in foreground. (Ryan and Harms) - Holston Army Ammunition Plant, RDX-and-Composition-B Manufacturing Line 9, Kingsport, Sullivan County, TN

  14. Fuel compositions containing maleic derivatives of 2,5-dimercapto-1,3,4-thiadiazole

    SciTech Connect

    Karol, T.J.

    1989-11-14

    This patent describes a diesel fuel composition. It is characterized by improved wear properties. It comprises: a major portion of middle distillates boiling in the range of about 163{degrees}to 400{degrees}C. and a minor wear improving amount of a reaction product of a maleic compound and 2,5-dimercapto-1,3,4-thiadiazole.

  15. Newsletter for Asian and Middle Eastern Languages on Computer, Volume 1, Numbers 3 & 4.

    ERIC Educational Resources Information Center

    Meadow, Anthony, Ed.

    1986-01-01

    Volume 1, numbers 3 and 4, of the newsletter on the use of non-Western languages with computers contains the following articles: "Reversing the Screen under MS/PC-DOS" (Dan Brink); "Comments on Diacritics Using Wordstar, etc. and CP/M Software for Non-Western Languages" (Michael Broschat); "Carving Tibetan in Silicon: A Tibetan Font for the…

  16. 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

  17. Individual and combined associations of genetic variants in CYP3A4, CYP3A5, and SLCO1B1 with simvastatin and simvastatin acid plasma concentrations

    PubMed Central

    Luzum, Jasmine A.; Theusch, Elizabeth; Taylor, Kent D.; Wang, Ann; Sadee, Wolfgang; Binkley, Philip F.; Krauss, Ronald M.; Medina, Marisa W.; Kitzmiller, Joseph P.

    2015-01-01

    Our objective was to evaluate the associations of genetic variants affecting simvastatin (SV) and simvastatin acid (SVA) metabolism (CYP3A4*22 and CYP3A5*3) and transport (SLCO1B1 T521C) with 12-hour plasma SV and SVA concentrations. The variants were genotyped, and concentrations were quantified by HPLC-MS/MS in 646 participants of the Cholesterol and Pharmacogenetics clinical trial of 40 mg/day SV for 6 weeks. The genetic variants were tested for association with 12-hour plasma SV, SVA, or the SVA/SV ratio using general linear models. CYP3A5*3 was not significantly associated with 12-hour plasma SV or SVA concentration. CYP3A4*1/*22 participants had 58% higher 12-hour plasma SV concentration compared to CYP3A4*1/*1 participants (p=0.006). SLCO1B1 521T/C and 521C/C participants had 71% (p<0.001) and 248% (p<0.001) higher 12-hour plasma SVA compared to SLCO1B1 521T/T participants, respectively. CYP3A4 and SLCO1B1 genotypes combined categorized participants into low (<1), intermediate (≈1), and high (>1) SVA/SV ratio groups (p=0.001). In conclusion, CYP3A4*22 and SLCO1B1 521C were significantly associated with increased plasma 12-hour concentrations of SV and SVA, respectively. CYP3A5*3 was not significantly associated with 12-hour plasma SV or SVA concentrations. The combination of CYP3A4*22 and SLCO1B1 521C was significantly associated with SVA/SV ratio, which may translate into different clinical SV risk/benefit profiles. PMID:26164721

  18. Bis(2-amino-5-methyl-1,3,4-thia­diazole-κN 3)dichloridocobalt(II)

    PubMed Central

    Song, Ye; Ji, Yu-Fei; Kang, Min-Yan; Liu, Zhi-Liang

    2012-01-01

    In the monomeric title complex, [CoCl2(C3H5N3S)2], the CoII atom is tetra­coordinated by two chloride anions and two N atoms from two monodentate 2-amino-5-methyl-1,3,4-thia­diazole ligands, giving a slightly distorted tetra­hedral stereochemistry [bond angle range about Co = 105.16 (12)–112.50 (10)°]. In the complex, the dihedral angle between the 1,3,4-thia­diazole planes in the two ligands is 72.8 (1)°. There are two intra­molecular N—H⋯Cl inter­actions in the complex unit, while in the crystal, inter­molecular N—H⋯N and N—H⋯Cl hydrogen bonds link these units into a two-dimensional layered structure parallel to (011). PMID:22719326

  19. (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.

  20. Analysis of pyridyloxobutyl and pyridylhydroxybutyl DNA adducts in extrahepatic tissues of F344 rats treated chronically with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.

    PubMed

    Zhang, Siyi; Wang, Mingyao; Villalta, Peter W; Lindgren, Bruce R; Upadhyaya, Pramod; Lao, Yanbin; Hecht, Stephen S

    2009-05-01

    The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are potent pulmonary carcinogens in rats. NNK and NNAL require metabolic activation to express their carcinogenicity. Cytochrome P450-catalyzed alpha-hydroxylation at the methyl position of NNK or NNAL generates reactive intermediates, which alkylate DNA to form pyridyloxobutyl (POB)-DNA adducts or pyridylhydroxybutyl (PHB)-DNA adducts. NNK is metabolized to NNAL in a reversible and stereoselective manner, and the tissue-specific retention of (S)-NNAL is believed to be important to the carcinogenicity of NNK. In the present study, we investigated the formation of POB- and PHB-DNA adducts in extrahepatic tissues of F344 rats treated chronically with NNK and (R)- and (S)-NNAL (10 ppm in the drinking water, 1-20 weeks). POB- and PHB-DNA adducts were quantified in nasal olfactory mucosa, nasal respiratory mucosa, oral mucosa, and pancreas of treated rats. Adduct formation in the nasal respiratory mucosa exceeded that in the other tissues. O(2)-[4-(3-Pyridyl)-4-oxobut-1-yl]thymidine (O(2)-POB-dThd) or O(2)-[4-(3-pyridyl)-4-hydroxybut-1-yl]thymidine (O(2)-PHB-dThd) was the major adduct, followed by 7-[4-(3-pyridyl)-4-oxobut-1-yl]guanine (7-POB-Gua) or 7-[4-(3-pyridyl)-4-hydroxybut-1-yl]guanine (7-PHB-Gua). There was a remarkable similarity in adduct formation between the NNK and the (S)-NNAL groups, both of which were distinctively different from that in the (R)-NNAL group. For example, in the nasal olfactory mucosa, POB-DNA adduct levels in the NNK and (S)-NNAL groups were not significantly different from each other, while (R)-NNAL treatment generated 6-33 times lower amounts of POB-DNA adducts than did NNK treatment. In contrast, (R)-NNAL treatment produced significantly higher levels of PHB-DNA adducts than did NNK or (S)-NNAL treatment. Similar trends were observed in the nasal respiratory mucosa, oral mucosa

  1. 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.

  2. Study of energetics and structure of 1,2,3-benzotriazin-4(3H)-one and its 1H and enol tautomers.

    PubMed

    Miranda, Margarida S; Matos, M Agostinha R; Morais, Victor M F; Liebman, Joel F

    2011-05-26

    This paper reports an experimental and computational study on the energetics of 1,2,3-benzotriazin-4(3H)-one. The standard (p° = 0.1 MPa) molar enthalpy of formation of solid 1,2,3-benzotriazin-4(3H)-one, at T = 298.15 K, was derived from its standard massic energy of combustion measured by static bomb combustion calorimetry in oxygen. The Calvet high-temperature vacuum sublimation technique was used to measure the respective standard molar enthalpy of sublimation at T = 298.15 K. From these two experimentally determined thermodynamic parameters, we have calculated the standard molar enthalpy of formation of 1,2,3-benzotriazin-4(3H)-one in the gas phase at T = 298.15 K, (200.9 ± 3.8) kJ·mol(-1). Interrelations between structure and energy for 1,2,3-benzotriazin-4(3H)-one, the tautomer 1,2,3-benzotriazin-4(1H)-one, and the enol tautomer 1,2,3-benzotriazin-4-ol were discussed based on density functional theory (DFT) calculations with the B3LYP hybrid functional and the 6-311++G(d,p) basis set. The gas-phase enthalpy of formation of 1,2,3-benzotriazin-4(3H)-one was estimated from quantum chemical calculations using the G3(MP2)//B3LYP composite method. Nucleus-independent chemical shifts (NICS) were also calculated with the purpose of analyzing the aromaticity of the benzenic and heterocyclic rings of the title molecule and others related tautomerically to it. PMID:21542570

  3. (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

  4. Chiral 1,3,4-oxadiazol-2-ones as highly selective FAAH inhibitors.

    PubMed

    Patel, Jayendra Z; Parkkari, Teija; Laitinen, Tuomo; Kaczor, Agnieszka A; Saario, Susanna M; Savinainen, Juha R; Navia-Paldanius, Dina; Cipriano, Mariateresa; Leppänen, Jukka; Koshevoy, Igor O; Poso, Antti; Fowler, Christopher J; Laitinen, Jarmo T; Nevalainen, Tapio

    2013-11-14

    In the present study, identification of chiral 1,3,4-oxadiazol-2-ones as potent and selective FAAH inhibitors has been described. The separated enantiomers showed clear differences in the potency and selectivity toward both FAAH and MAGL. Additionally, the importance of the chirality on the inhibitory activity and selectivity was proven by the simplification approach by removing a methyl group at the 3-position of the 1,3,4-oxadiazol-2-one ring. The most potent compound of the series, the S-enantiomer of 3-(1-(4-isobutylphenyl)ethyl)-5-methoxy-1,3,4-oxadiazol-2(3H)-one (JZP-327A, 51), inhibited human recombinant FAAH (hrFAAH) in the low nanomolar range (IC50 = 11 nM), whereas its corresponding R-enantiomer 52 showed only moderate inhibition toward hrFAAH (IC50 = 0.24 μM). In contrast to hrFAAH, R-enantiomer 52 was more potent in inhibiting the activity of hrMAGL compared to S-enantiomer 51 (IC50 = 4.0 μM and 16% inhibition at 10 μM, respectively). The FAAH selectivity of the compound 51 over the supposed main off-targets, MAGL and COX, was found to be >900-fold. In addition, activity-based protein profiling (ABPP) indicated high selectivity over other serine hydrolases. Finally, the selected S-enantiomers 51, 53, and 55 were shown to be tight binding, slowly reversible inhibitors of the hrFAAH.

  5. 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.

  6. Synthesis of 4-(aminoalkyl) substituted 1,3-dioxanes as potent NMDA and σ receptor antagonists.

    PubMed

    Utech, Tina; Köhler, Jens; Wünsch, Bernhard

    2011-06-01

    Elongation of the distance between the oxygen heterocycle and the basic amino moiety or ring expansion of the oxygen heterocycle of the NMDA receptor antagonists dexoxadrol and etoxadrol led to compounds with promising NMDA receptor affinity. Herein the combination of both structural features, i.e. elongation of the O-heterocycle--amine distance with a 1,3-dioxane ring is envisaged. The synthesis of aminoethyl-1,3-dioxanes 13, 22, 23 and 29 was performed by transacetalization of various acetals with pentane-1,3,5-triol, activation of the remaining free OH moiety with tosyl chloride and subsequent nucleophilic substitution. The corresponding 3-aminopropyl derivatives 33-35 were prepared by substitution of the tosylates with KCN and LiAlH4 reduction. The highest NMDA receptor affinity was found for 1,3-dioxanes with a phenyl and an ethyl residue at the acetalic position (23) followed by diphenyl (22) and monophenyl derivatives (13). Generally the NMDA affinity of primary amines is higher than the NMDA affinity of secondary and tertiary amines. Altogether the primary amine 23a (Ki=24 nM) represents the most promising NMDA receptor antagonist of this series exceeding the NMDA affinity of the mono-homologues (2-aminoethyl)-1,3-dioxolanes (3,4) and (aminomethyl)-1,3-dioxanes (5,6). Whereas the primary amine 23a turned out to be selective against σ1 and σ2 receptors the benzylamine 13d was identified as potent (Ki=19 nM) and selective σ1 antagonist, which showed extraordinarily high antiallodynic activity in the capsaicin assay. PMID:21444132

  7. 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.

  8. 1,3-Alternate Tetraamido-Azacalix[4]arenes as Selective Anion Receptors.

    PubMed

    Canard, Gabriel; Edzang, Judicaelle Andeme; Chen, Zhongrui; Chessé, Matthieu; Elhabiri, Mourad; Giorgi, Michel; Siri, Olivier

    2016-04-11

    Six tetraaza[1.1.1.1]cyclophane derivatives bearing peripheral amide groups were prepared according to two distinct synthetic strategies that depend on the connection pattern between the aryl units. NMR experiments combined with the X-ray structures of two tetraamide derivatives 4 b and 10 show that these cavitands adopt a 1,3-alternate conformation both in solution and in the solid state. Consequently, the four amide groups of the aza[1.1.1.1]-m,m,m,m-cyclophane isomer 10 can contribute to the same recognition process towards neutral water molecules or anion guests. NMR experiments, mass spectrometry analyses and single-crystal X-ray structures confirm the anion-binding ability of this receptor. Absorption spectrophotometric titrations in nonpolar solvents provided evidence for the selectivity of 10 to chloride anions in the halide series, with a corresponding association constant Ka reaching 2.5 × 10(6) m(-1). PMID:26938487

  9. Nazarov cyclization of 1,4-pentadien-3-ols: preparation of cyclopenta[b]indoles and spiro[indene-1,4'-quinoline]s.

    PubMed

    Wang, Zhiming; Xu, Xingzhu; Gu, Zhanshou; Feng, Wei; Qian, Houjun; Li, Zhengyi; Sun, Xiaoqiang; Kwon, Ohyun

    2016-02-14

    The first Lewis acid-catalyzed intramolecular interrupted Nazarov cyclization of 1,4-pentadien-3-ols is described. Using FeBr3 as the catalyst, a series of new substituted cyclopenta[b]indoles was prepared-through a sequence of Nazarov cyclization, nucleophilic amination, and isomerization-with good yields and high diastereo- and regioselectivities. A similar catalytic process was also developed for the synthesis of structurally interesting spiro[indene-1,4'-quinoline]s. PMID:26771024

  10. 3-(3,4,5-Trimethoxyphenylselenyl)-1H-indoles and their selenoxides as combretastatin A-4 analogs: microwave-assisted synthesis and biological evaluation.

    PubMed

    Wen, Zhiyong; Xu, Jingwen; Wang, Zhiwei; Qi, Huan; Xu, Qile; Bai, Zhaoshi; Zhang, Qian; Bao, Kai; Wu, Yingling; Zhang, Weige

    2015-01-27

    A series of 3-(3,4,5-trimethoxyphenylselenyl)-1H-indoles and their selenoxides were designed as a new class of combretastatin A-4 (CA-4) analogs. The B ring and the cis double bond of CA-4 were replaced by an indole moiety and selenium atom, respectively. A facile and efficient microwave-assisted synthesis of 3-arylselenylindoles was developed to prepare the target compounds, which were then evaluated for antiproliferative activity against three human cancer cell lines using an MTT assay. Most of these compounds exhibited significant antiproliferative activity, with some showing nanomolar IC50 values. Tubulin polymerization and immunostaining experiments revealed that 13a potently inhibited tubulin polymerization and disrupted tubulin microtubule dynamics in a similar manner to CA-4. Docking studies demonstrated that 13a adopts an orientation similar to that of CA-4 at the colchicine binding site on tubulin. PMID:25461319

  11. 3-(3,4,5-Trimethoxyphenylselenyl)-1H-indoles and their selenoxides as combretastatin A-4 analogs: microwave-assisted synthesis and biological evaluation.

    PubMed

    Wen, Zhiyong; Xu, Jingwen; Wang, Zhiwei; Qi, Huan; Xu, Qile; Bai, Zhaoshi; Zhang, Qian; Bao, Kai; Wu, Yingling; Zhang, Weige

    2015-01-27

    A series of 3-(3,4,5-trimethoxyphenylselenyl)-1H-indoles and their selenoxides were designed as a new class of combretastatin A-4 (CA-4) analogs. The B ring and the cis double bond of CA-4 were replaced by an indole moiety and selenium atom, respectively. A facile and efficient microwave-assisted synthesis of 3-arylselenylindoles was developed to prepare the target compounds, which were then evaluated for antiproliferative activity against three human cancer cell lines using an MTT assay. Most of these compounds exhibited significant antiproliferative activity, with some showing nanomolar IC50 values. Tubulin polymerization and immunostaining experiments revealed that 13a potently inhibited tubulin polymerization and disrupted tubulin microtubule dynamics in a similar manner to CA-4. Docking studies demonstrated that 13a adopts an orientation similar to that of CA-4 at the colchicine binding site on tubulin.

  12. Novel material for second harmonic generation: 3-Amino-1,2,4-triazolinium(1+) hydrogen L-tartrate

    NASA Astrophysics Data System (ADS)

    Matulková, Irena; Němec, Ivan; Císařová, Ivana; Němec, Petr; Mička, Zdeněk

    2007-05-01

    The X-ray structural analysis of 3-amino-1,2,4-triazolinium(1+) hydrogen L-tartrate has been carried out. This organic salt crystallises in the monoclinic space group P2 1, a = 7.7130(2) Å, b = 6.7690(2) Å, c = 9.2170(3) Å, β = 95.726(2)°, V = 478.81(2) Å 3, Z = 2, R = 0.0255 for 5922 observed reflections. The crystal structure is formed by a 3D network of hydrogen L-tartrate anions (interconnected by O-H ⋯O hydrogen bonds) with 3-amino-1,2,4-triazolinium(1+) cations located in the cavities of this network and connected with anions via N-H ⋯O and O-H ⋯N hydrogen bonds. The FTIR and FT Raman spectra were recorded, calculated and discussed. Quantitative measurements of second harmonic generation of powdered 3-amino-1,2,4-triazol-4-ium hydrogen L-tartrate at 800 nm were performed and a relative efficiency of 50% (compared to KDP) was observed.

  13. Histone H3K4 and K36 methylation, Chd1 and Rpd3S oppose the functions of Saccharomyces cerevisiae Spt4-Spt5 in transcription.

    PubMed

    Quan, Tiffani Kiyoko; Hartzog, Grant Ashley

    2010-02-01

    Spt4-Spt5, a general transcription elongation factor for RNA polymerase II, also has roles in chromatin regulation. However, the relationships between these functions are not clear. Previously, we isolated suppressors of a Saccharomyces cerevisiae spt5 mutation in genes encoding members of the Paf1 complex, which regulates several cotranscriptional histone modifications, and Chd1, a chromatin remodeling enzyme. Here, we show that this suppression of spt5 can result from loss of histone H3 lysines 4 or 36 methylation, or reduced recruitment of Chd1 or the Rpd3S complex. These spt5 suppressors also rescue the synthetic growth defects observed in spt5 mutants that also lack elongation factor TFIIS. Using a FLO8 reporter gene, we found that a chd1 mutation caused cryptic initiation of transcription. We further observed enhancement of cryptic initiation in chd1 isw1 mutants and increased histone acetylation in a chd1 mutant. We suggest that, as previously proposed for H3 lysine 36 methylation and the Rpd3S complex, H3 lysine 4 methylation and Chd1 function to maintain normal chromatin structures over transcribed genes, and that one function of Spt4-Spt5 is to help RNA polymerase II overcome the repressive effects of these histone modifications and chromatin regulators on transcription. PMID:19948887

  14. Discovery of 1-(1,3,5-triazin-2-yl)piperidine-4-carboxamides as inhibitors of soluble epoxide hydrolase.

    PubMed

    Thalji, Reema K; McAtee, Jeff J; Belyanskaya, Svetlana; Brandt, Martin; Brown, Gregory D; Costell, Melissa H; Ding, Yun; Dodson, Jason W; Eisennagel, Steve H; Fries, Rusty E; Gross, Jeffrey W; Harpel, Mark R; Holt, Dennis A; Israel, David I; Jolivette, Larry J; Krosky, Daniel; Li, Hu; Lu, Quinn; Mandichak, Tracy; Roethke, Theresa; Schnackenberg, Christine G; Schwartz, Benjamin; Shewchuk, Lisa M; Xie, Wensheng; Behm, David J; Douglas, Stephen A; Shaw, Ami L; Marino, Joseph P

    2013-06-15

    1-(1,3,5-Triazin-yl)piperidine-4-carboxamide inhibitors of soluble epoxide hydrolase were identified from high through-put screening using encoded library technology. The triazine heterocycle proved to be a critical functional group, essential for high potency and P450 selectivity. Phenyl group substitution was important for reducing clearance, and establishing good oral exposure. Based on this lead optimization work, 1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-{[[4-bromo-2-(trifluoromethoxy)]-phenyl]methyl}-4-piperidinecarboxamide (27) was identified as a useful tool compound for in vivo investigation. Robust effects on a serum biomarker, 9, 10-epoxyoctadec-12(Z)-enoic acid (the epoxide derived from linoleic acid) were observed, which provided evidence of robust in vivo target engagement and the suitability of 27 as a tool compound for study in various disease models.

  15. 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…

  16. Inhibition of carbonic anhydrases from the extremophilic bacteria Sulfurihydrogenibium yellostonense (SspCA) and S. azorense (SazCA) with a new series of sulfonamides incorporating aroylhydrazone-, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl moieties.

    PubMed

    Alafeefy, Ahmed M; Abdel-Aziz, Hatem A; Vullo, Daniela; Al-Tamimi, Abdul-Malek S; Al-Jaber, Nabila A; Capasso, Clemente; Supuran, Claudiu T

    2014-01-01

    A series of new sulfonamides was prepared starting from 2-oxo-N'-(4-sulfamoylphenyl)-propanehydrazonoyl chloride, a sulfanilamide derivative, which was reacted with aroylhydrazides, amines, or thiols. A library of derivatives incorporating aroylhydrazone, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenyl-methylene)-1,3,4-thiadiazol-3(2H)-yl moieties was thus synthesized. The new compounds were investigated as inhibitors of four α-carbonic anhydrases (CAs, EC 4.2.1.1), the human (h) isoforms hCA I and II, and the bacterial ones recently isolated from the extremophilic bacteria Sulfurihydrogenibium yellostonense (SspCA) and Sulfurihydrogenibium azorense (SazCA). Low nanomolar activity was observed against hCA II (KIs of 0.56-17.1 nM) whereas hCA I was less inhibited by these compounds (K(I)s of 86.4 nM-32.8 μM). The bacterial CAs were also effectively inhibited by these derivatives (K(I)s in the range of 0.77-234 nM against SazCA, and of 6.2-89.1 against SspCA, respectively), with several low nanomolar/subnanomolar inhibitors detected against both of them. As SspCA and SazCA are among the most thermostable and catalytically active CAs, it is of interest to find modulators of their activity for potential biotechnologic applications. PMID:24332658

  17. 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.

  18. 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.

  19. Simultaneously rapid synthesis and consolidation of nanostructured Mg0.3Al1.4Ti1.3O5 by high-frequency induction heating

    NASA Astrophysics Data System (ADS)

    Kang, Hyun-Su; Du, Song-Lee; Doh, Jung-Mann; Yoon, Jin-Kook; Shon, In-Jin

    2014-05-01

    A one-step synthesis and consolidation of nanostructured Mg0.3Al1.4Ti1.3O5 was achieved by high-frequency induction heating, using the stoichometric mixture of MgO, Al2O3 and TiO2 powders. Before sintering, the powder mixture was high-energy ball milled for 10 h. From the milled powder mixture, a highly dense nanostructured Mg0.3Al1.4Ti1.3O5 compound could be obtained within one minute, under the simultaneous application of 80 MPa pressure and an induced current. The advantage of this process is that it allows an instant densification to the near theoretical density, while sustaining the nanosized microstructure of raw powders. The sintering behavior, microstructure and mechanical properties of Mg0.3Al1.4Ti1.3O5 compound were evaluated.

  20. Strong electron correlation on the Fe3O4(0 0 1) surfaces

    NASA Astrophysics Data System (ADS)

    Pinto, Henry; Elliott, Simon D.; Foster, Adam; Nieminen, R. M.

    2007-03-01

    Magnetite Fe3O4 is a fascinating material that still is not well understood and presents challenges for the state-of-the-art computational methods. This transition metal oxide undergoes a first-order metal-insulator transition at TV=120 K. The ferrimagnetic properties of Fe3O4 makes it a promising material for spintronic applications. We use a plane wave density functional theory in the generalized gradient approximation adding a Hubbard-U parameter to describe properly the strongly correlated Fe--3d electrons. Based on previous results, we compute the surface structure, magnetic properties and electronic structure of several Fe3O4(0 0 1) surfaces with (√2x√2)R45^o reconstruction. The simulated scanning tunneling microscopy images of these surfaces are compared and discussed in the light of available experimental data. Finally, we analyze the possible existence of charge ordering on the Fe3O4(0 0 1) surface and the effect on the surface electronic structure with changing the value of the Hubbard-U parameter on the superficial Fe sites. H. Pinto, S. Elliott, J.Phys.: Condens. Matter 18, 10427 (2006)

  1. 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.

  2. Crystal structure of [propane-1,3-diylbis(piperidine-4,1-di­yl)]bis­[(pyridin-4-yl)methanone]–4,4′-oxydi­benzoic acid (1/1)

    PubMed Central

    Low, Emily M.; LaDuca, Robert L.

    2014-01-01

    In the title co-crystal, C25H32N4O2·C14H10O5, mol­ecules are connected into supra­molecular chains aligned along [102] by O—H⋯N hydrogen bonding. These aggregate into supra­molecular layers oriented parallel to (20-1) by C—H⋯O inter­actions. These layers then stack in an ABAB pattern along the c crystal direction to give the full three-dimensional crystal structure. The central chain in the dipyridylamide has an anti–anti conformation. The dihedral angle between the aromatic ring planes is 29.96 (3)°. Disorder is noted in some of the residues in the structure and this is manifested in two coplanar dispositions of one statistically disordered carb­oxy­lic acid group. PMID:25309203

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

    PubMed

    Low, Emily M; LaDuca, Robert L

    2014-09-01

    In the title co-crystal, C25H32N4O2·C14H10O5, mol-ecules are connected into supra-molecular chains aligned along [102] by O-H⋯N hydrogen bonding. These aggregate into supra-molecular layers oriented parallel to (20-1) by C-H⋯O inter-actions. These layers then stack in an ABAB pattern along the c crystal direction to give the full three-dimensional crystal structure. The central chain in the dipyridylamide has an anti-anti conformation. The dihedral angle between the aromatic ring planes is 29.96 (3)°. Disorder is noted in some of the residues in the structure and this is manifested in two coplanar dispositions of one statistically disordered carb-oxy-lic acid group. PMID:25309203

  4. 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. PMID:19719048

  5. General, Highly Selective Synthesis of 1,3- and 1,4-Difunctionalized Building Blocks by Regiodivergent Epoxide Opening.

    PubMed

    Funken, Nico; Mühlhaus, Felix; Gansäuer, Andreas

    2016-09-19

    We describe a regiodivergent epoxide opening (REO) featuring a catalyst-controlled synthesis of enantiomerically and diastereomerically highly enriched or pure syn- and anti- 1,3- and 1,4-difunctionalized building blocks from a common epoxide precursor. The REO is attractive for natural product synthesis and as a branching reaction for diversity-oriented synthesis with epoxides.

  6. General, Highly Selective Synthesis of 1,3- and 1,4-Difunctionalized Building Blocks by Regiodivergent Epoxide Opening.

    PubMed

    Funken, Nico; Mühlhaus, Felix; Gansäuer, Andreas

    2016-09-19

    We describe a regiodivergent epoxide opening (REO) featuring a catalyst-controlled synthesis of enantiomerically and diastereomerically highly enriched or pure syn- and anti- 1,3- and 1,4-difunctionalized building blocks from a common epoxide precursor. The REO is attractive for natural product synthesis and as a branching reaction for diversity-oriented synthesis with epoxides. PMID:27600090

  7. 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.

  8. 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.

  9. Studies on Absorption and Emission Characteristics of Inclusion Complexes of Some 4-Arylidenamino-5-phenyl-4H-1, 2, 4-triazole-3-thiols.

    PubMed

    Panda, Sunakar; Nayak, Sashikanta

    2016-03-01

    The inclusion complexes of a series of 4-arylidenamino-5-phenyl-4H-1, 2, 4-triazole-3-thiols have been prepared with β-cyclodextrin. The compounds and their inclusion complexes have been characterized by studying their physical and spectral properties. The thermodynamic stability constant and free energy of activation have been determined to know the stability of inclusion complexes and type of host-guest relation. Finally, absorption, excitation and emission spectra of the compounds (4-arylidenamino-5-phenyl-4H-1, 2, 4-triazole-3-thiols) and their inclusion complexes have been taken. It is found that inclusion complex formation brings about a drastic change in absorption and fluorescence characteristic (both excitation and emission spectra) of newly synthesized compounds.

  10. 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

    2014-04-01

    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.

  11. catena-Poly[[bis-(4-methyl-benzene-thiol-ato)cadium(II)]-μ-1,3-di-4-pyridylpropane].

    PubMed

    Zhang, Yan; Zhou, Yan; Han, Lei

    2009-03-28

    In the title compound, [Cd(C(7)H(7)S)(2)(C(13)H(14)N(2))](n), the unique Cd(II) ion, located on a twofold rotation axis, is coordinated by two S atoms and two N atoms in a slightly distorted tetra-hedral environment. Symmetry-related Cd(II) ions are linked via bridging 1,3-di-4-pyridylpropane ligands, forming a zig-zag chain-structure parallel to [001]. In the crystal structure, there are weak intra-chain π-π stacking inter-actions between benzene rings, with a centroid-centroid distance of 3.825 (7) Å, and pairs of chains are inter-digitated with respect to the 4-methyl-benzene-thiol-ate groups.

  12. Trans-4,4{prime}-dichloro-1,1{prime},2,2{prime},3,3{prime}-tetrathiadiazafulvalene (DC-TAF) and its 1:1 radical cation salts [DC-TAF][X]: Preparation and solid-state properties of BF{sub 4{minus}}, ClO{sub 4{minus}}, and FSO{sub 3{minus}} derivatives

    SciTech Connect

    Barclay, T.J.; Beer, L.; Cordes, A.W.; Haddon, R.C.; Itkis, M.I.; Oakley, R.T.; Preuss, K.E.; Reed, R.W.

    1999-07-21

    Reductive coupling of 4,5-dichloro-1,2,3-dithiazolylium chloride yields trans-4,4{prime}-dichloro-1,1{prime},2,2{prime},3,3{prime}-tetrathiadiazafulvalene (DC-TAF), the first example of this heterofulvalene system. Ab initio molecular orbital (B3LYP/6-31G**) calculations on prototypal TAF confirm that the closed shell {sup 1}A{sub g} state lies 22 kcal mol{sup {minus}1} below the {sup 3}B{sub u} diradical triplet. Cyclic voltammetry on DC-TAF reveals two reversible oxidation waves at 0.80and 1.25 V (in CH{sub 3}CN, reference SCE). The EST signal (g = 2.0117) of the radical cation [DC-TAF]{sup +} (in SO{sub 2}(1)) exhibits a five=line hyperfine coupling pattern with a{sub n} = 0.096 mT. DC-TAF forms a series of 1:1 radical ion salts [DC-TAF][X] by electrooxidation in the presence of tetrahedral counterions (X{sup {minus}} = BF{sub 4}{sup {minus}}, ClO{sub 4}{sup {minus}}, FSO{sub 3}{sup {minus}}). The crystal structures of these salts are isomorphous, monoclinic space group P2{sub 1}/n. and consist of one-dimensional ladder-like arrays of [DC-TAF]{sup +} radical cations bridged by S---S contacts ranging from 3.5 to 3.7 {angstrom}. Variable-temperature conductivity and magnetic measurements on [DC-TAF][ClO{sub 4}] indicate Mott insulator behavior, with a measured band gap of 0.30 eV.

  13. Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Antinociceptive Agents.

    PubMed

    Altıntop, Mehlika Dilek; Can, Özgür Devrim; Demir Özkay, Ümide; Kaplancıklı, Zafer Asım

    2016-01-01

    In the current work, new 1,3,4-thiadiazole derivatives were synthesized and investigated for their antinociceptive effects on nociceptive pathways of nervous system. The effects of these compounds against mechanical, thermal and chemical stimuli were evaluated by tail-clip, hot-plate and acetic acid-induced writhing tests, respectively. In addition, activity cage was performed to assess the locomotor activity of animals. The obtained data indicated that compounds 3b, 3c, 3d, 3e, 3g and 3h increased the reaction times of mice both in the hot-plate and tail-clip tests, indicating the centrally mediated antinociceptive activity of these compounds. Additionally, the number of writhing behavior was significantly decreased by the administration of compounds 3a, 3c, 3e and 3f, which pointed out the peripherally mediated antinociceptive activity induced by these four compounds. According to the activity cage tests, compounds 3a, 3c and 3f significantly decreased both horizontal and vertical locomotor activity of mice. Antinociceptive behavior of these three compounds may be non-specific and caused by possible sedative effect or motor impairments. PMID:27490523

  14. Above-threshold ionization near the 3p4d 1Fo autoionizing state in magnesium

    NASA Astrophysics Data System (ADS)

    Reber, A.; Baynard, T.; Martín, F.; Bachau, H.; Berry, R. S.

    2005-05-01

    Two-photon above-threshold ionization (ATI) relative cross sections from the 3P1 state of Mg have been measured using two-color ionization in the focus of a magnetic bottle spectrometer and have been calculated using the Green’s-function method in the Feshbach formalism and an L2 -integrable close-coupling approach, with a basis of L2 -integrable B -spline functions. We report these cross sections in the region of 3d4p Fo1 autoionizing state, with photon energies of 3.3-3.6eV . This is one of the few direct comparisons between ab initio theory and experiments in ATI in the vicinity of a Feshbach resonance. A good agreement between theory and experiment is found in the relative total cross sections.

  15. 1,3,8-Triazaspiro[4.5]decane-2,4-diones as efficacious pan-inhibitors of hypoxia-inducible factor prolyl hydroxylase 1-3 (HIF PHD1-3) for the treatment of anemia.

    PubMed

    Vachal, Petr; Miao, Shouwu; Pierce, Joan M; Guiadeen, Deodial; Colandrea, Vincent J; Wyvratt, Matthew J; Salowe, Scott P; Sonatore, Lisa M; Milligan, James A; Hajdu, Richard; Gollapudi, Anantha; Keohane, Carol A; Lingham, Russell B; Mandala, Suzanne M; DeMartino, Julie A; Tong, Xinchun; Wolff, Michael; Steinhuebel, Dietrich; Kieczykowski, Gerard R; Fleitz, Fred J; Chapman, Kevin; Athanasopoulos, John; Adam, Gregory; Akyuz, Can D; Jena, Dhirendra K; Lusen, Jeffrey W; Meng, Juncai; Stein, Benjamin D; Xia, Lei; Sherer, Edward C; Hale, Jeffrey J

    2012-04-12

    The discovery of 1,3,8-triazaspiro[4.5]decane-2,4-diones (spirohydantoins) as a structural class of pan-inhibitors of the prolyl hydroxylase (PHD) family of enzymes for the treatment of anemia is described. The initial hit class, spirooxindoles, was identified through affinity selection mass spectrometry (AS-MS) and optimized for PHD2 inhibition and optimal PK/PD profile (short-acting PHDi inhibitors). 1,3,8-Triazaspiro[4.5]decane-2,4-diones (spirohydantoins) were optimized as an advanced lead class derived from the original spiroindole hit. A new set of general conditions for C-N coupling, developed using a high-throughput experimentation (HTE) technique, enabled a full SAR analysis of the spirohydantoins. This rapid and directed SAR exploration has resulted in the first reported examples of hydantoin derivatives with good PK in preclinical species. Potassium channel off-target activity (hERG) was successfully eliminated through the systematic introduction of acidic functionality to the molecular structure. Undesired upregulation of alanine aminotransferese (ALT) liver enzymes was mitigated and a robust on-/off-target margin was achieved. Spirohydantoins represent a class of highly efficacious, short-acting PHD1-3 inhibitors causing a robust erythropoietin (EPO) upregulation in vivo in multiple preclinical species. This profile deems spirohydantoins as attractive short-acting PHDi inhibitors with the potential for treatment of anemia.

  16. Neurochemical and toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridine to rat serotonin neurons in dissociated cell cultures

    SciTech Connect

    Friedman, L.K.; Mytilineou, C. )

    1990-05-01

    Dissociated cell cultures from the pontine area of embryonic rat brain were used to study the sensitivity of serotonin (5-hydroxy-tryptamine (5-HT)) neurons to the neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP+). Treatment with MPTP (up to 100 microM) for 7 days did not cause degeneration of 5-HT neurons. A 50% inhibition of (3H)5-HT uptake caused by 100 microM MPTP was a direct effect on the 5-HT uptake carrier, reversed by washing for 7 days. Incubation of cultures with MPTP increased the intraneuronal levels of 5-HT and reduced the levels of 5-hydroxyindoleacetic acid, suggesting a reduction in 5-HT metabolism. MPTP reduced monoamine oxidase activity in the cultures, which probably led to the reduction in 5-HT metabolism. Exposure to MPP+ (0.5-10 microM) for 4 to 7 days decreased (3H)5-HT uptake and induced loss of neurons stained with antibodies against 5-HT. Comparison between 5-HT and dopamine (DA) neurons indicated a differential sensitivity to MPP+ toxicity with DA neurons being more susceptible. Analysis of the competition of MPP+ with the natural substrates for uptake sites of 5-HT and DA neurons demonstrated higher affinity of MPP+ for DA compared to 5-HT neurons. The lower affinity of MPP+ for 5-HT neurons could be responsible for the accumulation of lower MPP+ levels observed in pontine cultures and explain the resistance of 5-HT neurons to this toxin.

  17. Connecting modes of linking ligands containing different terminal groups (pyridyl-amine or pyridyl-pyridyl): Preparation and structures of {[Cd( L1) 2(OH 2) 2]·(ClO 4) 2·(C 6H 6)} ∞, {[Cd( L2) 2(ClO 4) 2]·(CH 3OH) 2} ∞, {[Cd( L3) 2(OH 2) 2]·(ClO 4) 2} ∞, and [Cd( L4) 2(CH 3OH) 2(ClO 4) 2] {( m-py)-CH dbnd N-(CH 3)C 6H 3-C 6H 3(CH 3)-NH 2 ( m = 3 ( L1) or 4 ( L2)); ( n-py)-CH dbnd N-(CH 3)C 6H 3-C 6H 3(CH 3)-N dbnd CH-( n-py); ( n = 3 ( L3) or 4 ( L4))}

    NASA Astrophysics Data System (ADS)

    Yun, Sung Yol; Lee, Kyung-Eun; Lee, Soon W.

    2009-10-01

    We prepared four potential linking ligands, [(3-py)-CH dbnd N-(CH 3)C 6H 3-C 6H 3(CH 3)-NH 2, L1], [(4-py)-CH dbnd N-(CH 3)C 6H 3-C 6H 3(CH 3)-NH 2, L2], [(3-py)-CH dbnd N-(CH 3)C 6H 3-C 6H 3(CH 3)-N dbnd CH-(3-py), L3], and [(4-py)-CH dbnd N-(CH 3)C 6H 3-C 6H 3(CH 3)-N dbnd CH-(4-py), L4], all of which contain an intervening biphenyl fragment. Whereas ligands L1 and L2 have two types of terminal groups (pyridyl-amine), ligands L3 and L4 have a single type of terminal groups (pyridyl-pyridyl). Ligands L1- L4 reacted with cadmium nitrate to produce {[Cd( L1) 2(OH 2) 2]·(ClO 4) 2·(C 6H 6)} ∞ ( 1), {[Cd( L2) 2(ClO 4) 2]·(CH 3OH) 2} ∞ ( 2), {[Cd( L3) 2(OH 2) 2]·(ClO 4) 2} ∞ ( 3), and [Cd( L4) 2(CH 3OH) 2(ClO 4) 2] ( 4), respectively. Whereas compounds 1- 3 are 1-dimensional coordination polymers, compound 4 is a discrete molecular species.

  18. Evidence of Polymorphism on the Antitrypanosomal Naphthoquinone (4E)-2-(1H-Pyrazol-3-ylamino)-4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one

    PubMed Central

    Sperandeo, Norma R.; Faudone, Sonia N.

    2013-01-01

    The aim of this study was to characterize the solid state properties of (4E)-2-(1H-pyrazol-3-ylamino)-4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one (BiPNQ), a compound with a significant inhibitory activity against Trypanosoma cruzi, the etiological agent of Chagas disease (American trypanosomiasis). Methods used included Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Fourier Transform Infrared Spectroscopy (FTIR), Powder X-Ray Diffraction (PXRD), Hot Stage, and Confocal Microscopy. Two BiPNQ samples were obtained by crystallization from absolute methanol and 2-propanol-water that exhibited different thermal behaviours, PXRD patterns, and FTIR spectra, indicating the existence of an anhydrous form (BiPNQ-I) and a solvate (BIPNQ-s), which on heating desolvated leading to the anhydrous modification BiPNQ-I. It was determined that FTIR, DSC, and PXRD are useful techniques for the characterization and identification of the crystalline modifications of BiPNQ. PMID:24106678

  19. Merlin's tumor suppression linked to inhibition of the E3 ubiquitin ligase CRL4DCAF1

    PubMed Central

    Li, Wei

    2010-01-01

    The mechanism by which the FERM domain protein Merlin, encoded by the tumor suppressor NF2, restrains cell proliferation is poorly understood. Prior studies have suggested that Merlin exerts its antimitogenic effect by interacting with multiple signaling proteins located at or near the plasma membrane. We have recently observed that Merlin translocates into the nucleus and binds to and inhibits the E3 ubiquitin ligase CRL4DCAF1. Genetic evidence indicates that inactivation of Merlin induces oncogenic gene expression, hyperproliferation, and tumorigenicity by unleashing the activity of CRL4DCAF1. In addition to providing a potential explanation for the diverse effects that loss of Merlin exerts in multiple cell types, these findings suggest that compounds inhibiting CRL4DCAF1 may display therapeutic efficacy in Neurofibromatosis type 2 and other cancers driven by Merlin inactivation. PMID:21084862

  20. Disposition and excretion of 14C-AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene) and 14c-hhcb (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-gamma-2-benzopyran) after intravenous administration to Sprague-Dawley rats and domestic pigs.

    PubMed

    Api, Anne Marie; Ritacco, Gretchen; Sipes, I Glenn

    2013-07-01

    7-Acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN ) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-benzopyran (HHCB) are polycyclic musks widely used as fragrance ingredients in consumer products. Because their metabolic fate following systemic exposure is not fully characterized, disposition and excretion of (14)C-AHTN- and (14)C-HHCB-derived radioactivity were studied in Sprague-Dawley rats and domestic pigs following a single intravenous dose. Rats administered with AHTN or HHCB excreted 21% or 28% of the radioactivity in urine and 67% or 61% in feces, respectively, within 7 days. In pigs administered AHTN or HHCB, 86% or 74% of the dose was excreted in the urine, and 12% or 15% in feces, respectively, during the 14-day collection period. Radioactivity in the whole blood and plasma of both species and tissues of rats declined steadily until the end of the study (28 days) for both the materials. Radioactivity in rat adipose tissue reached peak at 2 hours after dosing, decreasing steadily thereafter. Radioactivity in pig blood declined rapidly from 70 ng equivalents/g at 10 minutes to 1 ng equivalent/g or less by 28 days after administration of either AHTN or HHCB. Radioactivity in pig skin and adipose tissue decreased to below the limit of detection by 28 days for both the materials. Thin-layer chromatography showed multiple radioactive components in both species' urine after administration of either material. Components found in the urine of the 2 species were qualitatively similar but quantitatively different. Both AHTN and HHCB were completely metabolized and excreted. No unchanged parent compound was detected in rat or pig urine.

  1. α(1,3)-Fucosyltransferases FUT4 and FUT7 Control Murine Susceptibility to Thrombosis

    PubMed Central

    Wang, Huili; Morales-Levy, Maria; Rose, Jason; Mackey, Lantz C.; Bodary, Peter; Eitzman, Daniel; Homeister, Jonathon W.

    2014-01-01

    The α(1,3)-fucosyltransferases, types IV and VII (FUT4 and FUT7, respectively), are required for the synthesis of functional selectin-type leukocyte adhesion molecule ligands. The selectins and their ligands modulate leukocyte trafficking, and P-selectin and its ligand, P-selectin glycoprotein ligand-1, can modulate hemostasis and thrombosis. Regulation of thrombosis by FUT4 and/or FUT7 activity was examined in mouse models of carotid artery thrombosis and collagen/epinephrine-induced thromboembolism. Mice lacking both FUT4 and FUT7 (Fut−/− mice) had a shorter time to occlusive thrombus formation in the injured carotid artery and a higher mortality due to collagen/epinephrine-induced pulmonary thromboemboli. Mice lacking P-selectin or P-selectin glycoprotein ligand-1 did not have a prothrombotic phenotype. Whole blood platelet aggregation was enhanced, and plasma fibrinogen content, clot weight, and clot strength were increased in Fut−/− mice, and in vitro clot lysis was reduced compared with wild type. Fut4−/−, but not Fut7−/−, mice had increased pulmonary thromboembolism-induced mortality and decreased thromboemboli dissolution in vivo. These data show that FUT4 and FUT7 activity regulates thrombosis in a P-selectin– and P-selectin glycoprotein ligand-1–independent manner and suggest that FUT4 activity is important for thrombolysis. PMID:23562273

  2. Aspirin Breaks the Crosstalk between 3T3-L1 Adipocytes and 4T1 Breast Cancer Cells by Regulating Cytokine Production.

    PubMed

    Hsieh, Chia-Chien; Huang, Yu-Shan

    2016-01-01

    Breast cancer is one of the most common cancers in women worldwide. The obesity process is normally accompanied by chronic, low-grade inflammation. Infiltration by inflammatory cytokines and immune cells provides a favorable microenvironment for tumor growth, migration, and metastasis. Epidemiological evidence has shown that aspirin is an effective agent against several types of cancer. The aim of this study is to investigate the anti-inflammatory and anti-cancer effects of aspirin on 3T3-L1 adipocytes, 4T1 murine breast cancer cells, and their crosstalk. The results showed that aspirin treatment inhibited differentiation and lipid accumulation by 3T3-L1 preadipocytes, and decreased the secretion of the inflammatory adipokine MCP-1 after stimulation with tumor necrosis factor (TNF)-α or conditioned medium from RAW264.7 cells. In 4T1 cells, treatment with aspirin decreased cell viability and migration, possibly by suppressing MCP-1 and VEGF secretion. Subsequently, culture of 4T1 cells in 3T3-L1 adipocyte-conditioned medium (Ad-CM) and co-culture of 3T3-L1 and 4T1 cells using a transwell plate were performed to clarify the relationship between these two cell lines. Aspirin exerted its inhibitory effects in the transwell co-culture system, as well as the conditioned-medium model. Aspirin treatment significantly inhibited the proliferation of 4T1 cells, and decreased the production of MCP-1 and PAI-1 in both the Ad-CM model and co-culture system. Aspirin inhibited inflammatory MCP-1 adipokine production by 3T3-L1 adipocytes and the cell growth and migration of 4T1 cells. It also broke the crosstalk between these two cell lines, possibly contributing to its chemopreventive properties in breast cancer. This is the first report that aspirin's chemopreventive activity supports the potential application in auxiliary therapy against obesity-related breast cancer development. PMID:26794215

  3. Aspirin Breaks the Crosstalk between 3T3-L1 Adipocytes and 4T1 Breast Cancer Cells by Regulating Cytokine Production.

    PubMed

    Hsieh, Chia-Chien; Huang, Yu-Shan

    2016-01-01

    Breast cancer is one of the most common cancers in women worldwide. The obesity process is normally accompanied by chronic, low-grade inflammation. Infiltration by inflammatory cytokines and immune cells provides a favorable microenvironment for tumor growth, migration, and metastasis. Epidemiological evidence has shown that aspirin is an effective agent against several types of cancer. The aim of this study is to investigate the anti-inflammatory and anti-cancer effects of aspirin on 3T3-L1 adipocytes, 4T1 murine breast cancer cells, and their crosstalk. The results showed that aspirin treatment inhibited differentiation and lipid accumulation by 3T3-L1 preadipocytes, and decreased the secretion of the inflammatory adipokine MCP-1 after stimulation with tumor necrosis factor (TNF)-α or conditioned medium from RAW264.7 cells. In 4T1 cells, treatment with aspirin decreased cell viability and migration, possibly by suppressing MCP-1 and VEGF secretion. Subsequently, culture of 4T1 cells in 3T3-L1 adipocyte-conditioned medium (Ad-CM) and co-culture of 3T3-L1 and 4T1 cells using a transwell plate were performed to clarify the relationship between these two cell lines. Aspirin exerted its inhibitory effects in the transwell co-culture system, as well as the conditioned-medium model. Aspirin treatment significantly inhibited the proliferation of 4T1 cells, and decreased the production of MCP-1 and PAI-1 in both the Ad-CM model and co-culture system. Aspirin inhibited inflammatory MCP-1 adipokine production by 3T3-L1 adipocytes and the cell growth and migration of 4T1 cells. It also broke the crosstalk between these two cell lines, possibly contributing to its chemopreventive properties in breast cancer. This is the first report that aspirin's chemopreventive activity supports the potential application in auxiliary therapy against obesity-related breast cancer development.

  4. Temperature dependence of alpha-induced scintillation in the 1,1,4,4-tetraphenyl-1,3-butadiene wavelength shifter

    NASA Astrophysics Data System (ADS)

    Veloce, L. M.; Kuźniak, M.; Di Stefano, P. C. F.; Noble, A. J.; Boulay, M. G.; Nadeau, P.; Pollmann, T.; Clark, M.; Piquemal, M.; Schreiner, K.

    2016-06-01

    Liquid noble based particle detectors often use the organic wavelength shifter 1,1,4,4-tetraphenyl-1,3-butadiene (TPB) which shifts UV scintillation light to the visible regime, facilitating its detection, but which also can scintillate on its own. Dark matter searches based on this type of detector commonly rely on pulse-shape discrimination (PSD) for background mitigation. Alpha-induced scintillation therefore represents a possible background source in dark matter searches. The timing characteristics of this scintillation determine whether this background can be mitigated through PSD. We have therefore characterized the pulse shape and light yield of alpha induced TPB scintillation at temperatures ranging from 300 K down to 4 K, with special attention given to liquid noble gas temperatures. We find that the pulse shapes and light yield depend strongly on temperature. In addition, the significant contribution of long time constants above ~50 K provides an avenue for discrimination between alpha decay events in TPB and nuclear-recoil events in noble liquid detectors.

  5. 5-(4-Chloro-phen-yl)-1-(2,4-dichloro-phen-yl)-4-methyl-1H-pyrazole-3-carboxylic acid.

    PubMed

    Wang, Wei; Fang, Zheng

    2008-11-22

    The asymmetric unit of the title compound, C(17)H(11)Cl(3)N(2)O(2), contains two independent mol-ecules; the pyrazole rings are oriented with respect to the chloro-phenyl and dichloro-phenyl rings at dihedral angles of 43.00 (3) and 65.06 (4)°, respectively, in one mol-ecule, and 51.17 (3) and 69.99 (3)°, respectively, in the other. Pairs of inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into dimers. In the crystal structure, there are π-π contacts between the pyrazole rings and dichloro-phenyl rings [centroid-centroid distances = 3.859 (3) and 3.835 (3) Å].

  6. 5-(4-Chloro­phen­yl)-1-(2,4-dichloro­phen­yl)-4-methyl-1H-pyrazole-3-carboxylic acid

    PubMed Central

    Wang, Wei; Fang, Zheng

    2008-01-01

    The asymmetric unit of the title compound, C17H11Cl3N2O2, contains two independent mol­ecules; the pyrazole rings are oriented with respect to the chloro­phenyl and dichloro­phenyl rings at dihedral angles of 43.00 (3) and 65.06 (4)°, respectively, in one mol­ecule, and 51.17 (3) and 69.99 (3)°, respectively, in the other. Pairs of inter­molecular O—H⋯O hydrogen bonds link the mol­ecules into dimers. In the crystal structure, there are π–π contacts between the pyrazole rings and dichloro­phenyl rings [centroid–centroid distances = 3.859 (3) and 3.835 (3) Å]. PMID:21581382

  7. Synthesis and structure of 1-methyl-2,3-dihydro-1,2,4-triazolium salts and their free bases

    SciTech Connect

    Pinson, V.V.; Krustalev, V.A.; Matveeva, Z.M.; Zelenin, K.N.

    1985-04-01

    1-Methyl-2,3-dihydro-1,2,4-triazolium iodides can be obtained by reacting methylhydrazones with S-methylthioamide hydriodides, by condensing 2-methylamidrazone hydriodides with aldehydes and ketones, or by reacting methyl iodide with 1-alkylidene(or arylidene) benzamidrazones. In solutions these salts are capable of undergoing tautomerism to 1-alkylidene(or arylidene)-2-methylamidrazone hydriodides. The influence of the structural factors on the position of the tautomeric equilibrium has been studied. The free bases obtained by neutralization of the respective salts by an alkali metal hydroxide are heretofore undescribed 1-alkylidene(or arylidene)-2-methylhydrazidoimines or 4-triazolines, depending on their structure. Under the action of oxygen, these compounds are readily oxidized to substituted 1-methyl-1,2,4-triazoles with heating.

  8. Aβ-Induced Synaptic Alterations Require the E3 Ubiquitin Ligase Nedd4-1

    PubMed Central

    Rodrigues, Elizabeth M.; Scudder, Samantha L.; Goo, Marisa S.

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative disease in which patients experience progressive cognitive decline. A wealth of evidence suggests that this cognitive impairment results from synaptic dysfunction in affected brain regions caused by cleavage of amyloid precursor protein into the pathogenic peptide amyloid-β (Aβ). Specifically, it has been shown that Aβ decreases surface AMPARs, dendritic spine density, and synaptic strength, and also alters synaptic plasticity. The precise molecular mechanisms by which this occurs remain unclear. Here we demonstrate a role for ubiquitination in Aβ-induced synaptic dysfunction in cultured rat neurons. We find that Aβ promotes the ubiquitination of AMPARs, as well as the redistribution and recruitment of Nedd4-1, a HECT E3 ubiquitin ligase we previously demonstrated to target AMPARs for ubiquitination and degradation. Strikingly, we show that Nedd4-1 is required for Aβ-induced reductions in surface AMPARs, synaptic strength, and dendritic spine density. Our findings, therefore, indicate an important role for Nedd4-1 and ubiquitin in the synaptic alterations induced by Aβ. SIGNIFICANCE STATEMENT Synaptic changes in Alzheimer's disease (AD) include surface AMPAR loss, which can weaken synapses. In a cell culture model of AD, we found that AMPAR loss correlates with increased AMPAR ubiquitination. In addition, the ubiquitin ligase Nedd4-1, known to ubiquitinate AMPARs, is recruited to synapses in response to Aβ. Strikingly, reducing Nedd4-1 levels in this model prevented surface AMPAR loss and synaptic weakening. These findings suggest that, in AD, Nedd4-1 may ubiquitinate AMPARs to promote their internalization and weaken synaptic strength, similar to what occurs in Nedd4-1's established role in homeostatic synaptic scaling. This is the first demonstration of Aβ-mediated control of a ubiquitin ligase to regulate surface AMPAR expression. PMID:26843640

  9. Spectral and quantum chemical studies on 1,3-bis(N(1)-4-amino-6-methoxypyrimidinebenzenesulfonamide-2,2,4,4-ethane-1,2-dithiol)-2,4-dichlorocyclodiphosph(V)azane and its erbium complex.

    PubMed

    Al-Mogren, Muneerah M; Alaghaz, Abdel-Nasser M A; El-Gogary, Tarek M

    2014-01-24

    Novel 1,3-bis(N(1)-4-amino-6-methoxypyrimidine-benzenesulfonamide-2,2,4,4-ethane-1,2-dithiol)-2,4-dichlorocyclodiphosph(V)azane (L), was prepared and their coordinating behavior towards the lanthanide ion Er(III) was studied. The structures of the isolated products are proposed based on elemental analyses, IR, UV-VIS., (1)H NMR, (13)C NMR, (31)P NMR, SEM, XRD, mass spectra, effective magnetic susceptibility measurements and thermogravimetric analysis (TGA). Computational studies have been carried out at the DFT-B3LYP/6-31G(d) level of theory on the structural and spectroscopic properties of L and its binuclear Er(III) complex. Different tautomers of the ligand were optimized at the ab initio DFT level. Keto-form structure is about 17.7 kcal/mol more stable than the enol form (taking zpe correction into account). Simulated IR frequencies were scaled and compared with that experimentally measured. TD-DFT method was used to compute the UV-VIS spectra which compared by the measured electronic spectra.

  10. Synthesis and Antimicrobial Screening of Novel Thioglycosides and Acyclonucleoside Analogs Carrying 1,2,3-Triazole and 1,3,4-Oxadiazole Moieties.

    PubMed

    Aouad, M R

    2016-01-01

    The solvent-free 1,3-dipolar cycloaddition reaction of dimethylacetylene dicarboxylate (1) with 2-chlorophenyl azide (2) afforded 1,2,3-triazole diester 3 that upon hydrazinolysis, furnished the corresponding bis-acid hydrazide 4. The treatment of compound 4 with carbon disulfide in a refluxing potassium hydroxide solution furnished the desired bis-1,3,4-oxadiazole-2-thione 5 tethered to a 1,2,3-triazole moiety. The respective SOx-glycosides 9-11 were obtained by glycosylation of bis-oxadiazole 5 with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide (6), 2,3,4,6-tetra-O-acetyl-α-d-galactopyranosyl bromide (7), and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl chloride (8) in dry acetone in the presence of Et3N, which acted as a base. However, alkylation of 5 with halogeno-alkanol 12 or 13, chloroglycerol 14, bromoethers 20 or 21, and epichlohydrin 22 in the presence of K2CO3 in DMF yielded the corresponding acyclonucleoside analogs 16-18 and 23-25. The isopropylidenes 19 and acetyl derivatives 26-28 of the products were also prepared. The newly synthesized compounds were characterized by (1)H NMR, (13)C NMR, 2D NMR, and mass spectra. The compounds were screened for their antibacterial and antifungal activities. A number of the tested compounds exhibited significant antimicrobial activity compared to the reference drugs.

  11. Steady-state photoconductivity of amorphous (As4S3Se3)1-x:Snx films

    NASA Astrophysics Data System (ADS)

    Iaseniuc, O. V.; Iovu, M. S.; Cojocaru, I. A.; Prisacar, A. M.

    2015-02-01

    Amorphous arsenic trisulfide (As2S3) and arsenic triselenide (As2Se3) are among widely investigated amorphous materials due to its interesting electrical, optical and photoelectrical properties. In order to improve the physical properties and recording characteristics, and to extend the spectral range of photosensibility, a special interest represents the mixed amorphous materials, like (As2S3):(As2Se3). Chalcogenide vitreous semiconductors (ChVS) of the As-S-Se system exhibit photostructural transformations with reversible and irreversible properties, and are promising materials as registration media for holography and optical information, for fabrication of diffractive elements, and other optoelectronic applications. Because many optoelectronic devices on amorphous semiconductors are based on the photoconductivity effect, special interests represent investigation of the stationary and non-stationary characteristics of photoconductivity. In this paper the experimental results of steady-state photoconductivity and holographic characteristics of amorphous (As4S3Se3)1-x:Snx thin films are presented. It was shown that the photoconductivity spectra depend on the polarity on the top illuminated electrode and on the Sn concentration in the host glass. The photosensitivity of amorphous ((As4S3Se3)1-x:Snx thin films is almost constant for all Sn-containing glasses. The Moss rule was used for determination of the optical forbidden gap Eg from the photoconductivity spectra. It was demonstrated that the investigated amorphous films are sensitive to the light irradiation and can be used as effective registration media for holographic information. The relaxation of photodarkening in amorphous (As4S3Se3)1-x:Snx thin films was investigated and was shown that the relaxation curves of transmittance T/T0 = f(t) can be described the stretch exponential function T(t)/T(0) = A0+Aexp[-(t-t0)/τ] (1-β) . The kinetics of diffraction efficiency growth η(t) was measured by registration of

  12. Crystal structure of 1',1''-dimethyl-4'-(4-cholorophen-yl)di-spiro-[11H-indeno[1,2-b]quinoxaline-11,2'-pyrrolidine-3',3''-piperidin]-4''-one.

    PubMed

    Nagalakshmi, R A; Suresh, J; Malathi, K; Kumar, R Ranjith; Lakshman, P L Nilantha

    2015-02-01

    In the title compound, C30H27ClN4O, the central pyrrolidine ring adopts an envelope conformation with the methyl-ene C atom being the flap. The quinoxaline and indane rings are each essentially planar, with r.m.s. deviations of 0.027 (1) and 0.0417 (1) Å, respectively. The pyrrolidine ring forms dihedral angles of 88.25 (1) and 83.76 (1)° with the quinoxaline and indane rings, respectively. A weak intra-molecular C-H⋯N inter-action is observed. In the crystal, C-H⋯π inter-actions lead to supra-molecular chains along [101] that assemble in the ac plane. Connections along the b axis are of the type Cl⋯Cl [3.6538 (16) Å].

  13. Design, Synthesis, and Biological Evaluation of (3R)-1,2,3,4-Tetrahydro-7-hydroxy-N-[(1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2-methylpropyl]-3-isoquinolinecarboxamide (JDTic) Analogues: In Vitro Pharmacology and ADME Profile

    PubMed Central

    2015-01-01

    JDTic analogues 4–15 which have the hydroxyl groups replaced with other groups were synthesized and their in vitro efficacy at the μ, δ, and κ opioid receptors determined and compared to JDTic using [35S]GTPγS assays. Compounds 4, 5, 6, 13, 14, and 15 had Ke = 0.024, 0.01, 0.039, 0.02, 0.11, and 0.041 nM compared to the Ke = 0.02 nM for JDTic at the κ receptor and were highly selective for the κ receptor relative to the μ and δ opioid receptors. Unexpectedly, replacement of the 3-hydroxyl substituent of the 4-(3-hydroxyphenyl) group of JDTic with a H, F, or Cl substituent leads to potent and selective KOR antagonists. In vitro studies to determine various ADME properties combined with calculated TPSA, clogP, and logBB values suggests that the potent and selective κ opioid receptors 4, 5, 13, and 14 deserve consideration for further development toward potential drugs for CNS disorders. PMID:25133923

  14. 40 CFR 721.10710 - 4, 7-Methano-1H-indene, 3a, 4, 7, 7a-tetrahydro-, polymer with 2-methyl-1, 3-butadiene and 5-(1...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 4, 7-Methano-1H-indene, 3a, 4, 7, 7a-tetrahydro-, polymer with 2-methyl-1, 3-butadiene and 5-(1-methylethenyl)bicyclo hept-2-ene. 721.10710 Section 721.10710 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES...

  15. ND4FeBr3, a new one-dimensional S=1 antiferromagnet

    NASA Astrophysics Data System (ADS)

    Harrison, A.; Stager, C. V.; Visser, D.

    1991-04-01

    Compounds of chemical formula AFeX3 (A=Rb,Cs,Tl, and X=Cl, Br) provide an isomorphous series of one-dimensional induced-moment magnets with an effective spin S=1. They display a variety of ordered magnetic structures at low temperatures, depending on the sign and relative magnitudes of the intra- and interchain exchange and any magnetic dipole-dipole interactions. We report the first preparation of the salt NH4FeBr3. Powder neutron diffraction measurements on a perdeuterated sample showed that at room temperature the unit cell is hexagonal with cell parameters a=7.398(3) Å and c=6.331(2) Å. On cooling, structural phase transitions to cells of successively lower symmetry were observed. These are probably caused by cooperative reorientations of the ND+4 tetrahedra. At 4.8(2) K and 2.8(2) K additional Bragg peaks were observed. These additional reflections were attributed to magnetic long-range order with antiferromagnetic exchange both in the basal plane and along the c axis and could be indexed on an orthorhombic unit cell of dimension 2a ×√ 3a × c. Magnetic susceptibility measurements taken with a SQUID magnetometer on a polycrystalline sample at 2-100 K with an applied magnetic field of 0.1 T showed very similar behavior to that for RbFeBr3, with a broad cusp at approximately 8 K and θ≂-43 K.

  16. 3,4-Dimeth­oxy-4′-nitro-1,1′-biphen­yl

    PubMed Central

    Li, Xin-Min; Hou, Yan-Jun; Chu, Wen-Yi; Sun, Zhi-Zhong

    2012-01-01

    The title compound, C14H13NO4, was prepared through a palladium-catalysed Suzuki–Miyaura coupling reaction. The asymmetric unit comprises two mol­ecules related by pseudo-inversion symmetry. The dihedral angles between the benzene rings in the two mol­ecules are 44.30 (6) and 48.50 (6)° while those between the benzene ring and the nitro group are 6.54 (13) and 5.73 (10)°. The crystal packing is defined only by Van der Waals inter­actions. PMID:22590202

  17. Synthesis, crystal structure, optical, electrochemical and thermal properties of the ynamide: Bis-(N-4-methylbenzenesulfonyl, N-n-butyl)-1,3-butadiyne-1,4-diamide

    NASA Astrophysics Data System (ADS)

    Doan, Thu-Hong; Talbi, Imen; Lohier, Jean-François; Touil, Soufiane; Alayrac, Carole; Witulski, Bernhard

    2016-07-01

    The novel ynamide compound, bis-(N-4-methylbenzenesulfonyl, N-n-butyl)-1,3-butadiyne-1,4-diamide (3), was synthesized and characterized by single crystal X-ray diffraction, 1H and 13C NMR, UV-fluorescence spectroscopy, cyclic voltammetry, TGA and DSC techniques. This first reported X-ray structure of a 1,3-butadiyne-1,4-diamide revealed that the amido substituents of 3 adopt a twisted conformation in the crystal with a torsion angle of 76.6° resulting in a molecule with axial chirality. The crystal structure of compound 3 is stabilized by intermolecular CH-π interactions that give pairs of stacked bis-alkyne-3 units. HOMO/LUMO energy levels of 3 were experimentally determined by means of electrochemical and optical methods to be -5.87/-1.98 eV respectively. The solid state polymerization of the title compound was investigated by differential scanning calorimetry (DSC) revealing that polymerization proceeded simultaneously to the phase transition assigned to the melting of 3. The solid state polymerization of 3 is discussed of being a topochemically initiated polymer chain reaction that proceeds with a non-topochemical chain growth.

  18. A Library of 1,4-Disubstituted 1,2,3-Triazole Analogs of Oxazolidinone RNA-Binding Agents

    PubMed Central

    Acquaah-Harrison, George; Zhou, Shu; Hines, Jennifer V.; Bergmeier, Stephen C.

    2010-01-01

    The design and synthesis of small molecules that target RNA is immensely important in antibacterial therapy. We had previously reported on the RNA binding of a series of 4,5-disubstituted 2-oxazolidinones that bind to a highly conserved bulge region of bacterial RNA. This biological target T box antitermination system, which is found mainly in Gram-positive bacteria, regulates the expression of several amino acid related genes. In an effort to amplify our library, we have prepared a library of 1,4-disubstituted 1,2,3-triazole analogs that entails an isosteric replacement of the oxazolidinone nucleus. The synthesis of the new analogs was enhanced via copper(I) catalysis of an azide and alkyne cycloaddition reaction. A total of 108 1,4-disubstituted 1,2,3-triazole compounds have been prepared. All compounds were evaluated as RNA binding agents. PMID:20557032

  19. Crystal structures of 2-acetyl-4-ethynylphenol and 2-acetyl-4-(3-hy­droxy-3-methylbut-1-yn-1-yl)phenol

    PubMed Central

    Hübscher, Jörg; Rosin, Robert; Seichter, Wilhelm; Weber, Edwin

    2016-01-01

    In the title compounds, C10H8O2, (I), and C13H14O3, (II), the 2-acetyl-4-ethynylphenol unit displays a planar geometry, which is stabilized by an intra­molecular O—H⋯O hydrogen bond. The crystal structure of (I) is constructed of infinite strands, along [101], of C—H⋯O=C hydrogen-bonded mol­ecules, which in turn are linked by C—H⋯π inter­actions. In the crystal of (II), which crystallized with three independent mol­ecules per asymmetric unit, the non-polar parts of the mol­ecules form hydro­phobic layered domains, parallel to (10-1), which are separated by the polar groups. While the 2-acetyl­phenol part of the mol­ecules are involved in O—H⋯O=C hydrogen bonding, the ternary OH groups creates a cyclic pattern of O—H⋯O hydrogen bonds. PMID:27746920

  20. Agriculture, Levels 1-4. Agriculture & Commercial Horticulture, Levels 1-4. Commercial Horticulture, Levels 1-3. Environmental Conservation, Levels 2-4. National Vocational Qualifications.

    ERIC Educational Resources Information Center

    Business and Technology Education Council, London (England).

    Britain's National Vocational Qualifications (NVQs) are work qualifications that measure what an employee or potential employee can do as well as how much he or she knows and understands about a particular job. Used as written proof of usable workplace skills that can be put to profitable use by an employer, NVQs range from basic Level 1, for…

  1. Interpretation of 3D void measurements with Tripoli4.6/JEFF3.1.1 Monte Carlo code

    SciTech Connect

    Blaise, P.; Colomba, A.

    2012-07-01

    The present work details the first analysis of the 3D void phase conducted during the EPICURE/UM17x17/7% mixed UOX/MOX configuration. This configuration is composed of a homogeneous central 17x17 MOX-7% assembly, surrounded by portions of 17x17 1102 assemblies with guide-tubes. The void bubble is modelled by a small waterproof 5x5 fuel pin parallelepiped box of 11 cm height, placed in the centre of the MOX assembly. This bubble, initially placed at the core mid-plane, is then moved in different axial positions to study the evolution in the core of the axial perturbation. Then, to simulate the growing of this bubble in order to understand the effects of increased void fraction along the fuel pin, 3 and 5 bubbles have been stacked axially, from the core mid-plane. The C/E comparison obtained with the Monte Carlo code Tripoli4 for both radial and axial fission rate distributions, and in particular the reproduction of the very important flux gradients at the void/water interfaces, changing as the bubble is displaced along the z-axis are very satisfactory. It demonstrates both the capability of the code and its library to reproduce this kind of situation, as the very good quality of the experimental results, confirming the UM-17x17 as an excellent experimental benchmark for 3D code validation. This work has been performed within the frame of the V and V program for the future APOLL03 deterministic code of CEA starting in 2012, and its V and V benchmarking database. (authors)

  2. Traf2 interacts with Smad4 and regulates BMP signaling pathway in MC3T3-E1 osteoblasts

    SciTech Connect

    Shimada, Koichi; Ikeda, Kyoko; Ito, Koichi

    2009-12-18

    Bone morphogenetic proteins (BMPs) play important roles in osteoblast differentiation and maturation. In mammals, the BMP-induced receptor-regulated Smads form complexes with Smad4. These complexes translocate and accumulate in the nucleus, where they regulate the transcription of various target genes. However, the function of Smad4 remains unclear. We performed a yeast two-hybrid screen using Smad4 as bait and a cDNA library derived from bone marrow, to indentify the proteins interacting with Smad4. cDNA clones for Tumor necrosis factor (TNF) receptor-associated factor 2 (Traf2) were identified, and the interaction between the endogenous proteins was confirmed in the mouse osteoblast cell line MC3T3-E1. To investigate the function of Traf2, we silenced it with siRNA. The level of BMP-2 protein in the medium, the expression levels of the Bmp2 gene and BMP-induced transcription factor genes, including Runx2, Dlx5, Msx2, and Sp7, and the phosphorylated-Smad1 protein level were increased in cells transfected with Traf2 siRNA. The nuclear accumulation of Smad1 increased with TNF-{alpha} stimulation for 30 min at Traf2 silencing. These results suggest that the TNF-{alpha}-stimulated nuclear accumulation of Smad1 may be dependent on Traf2. Thus, the interaction between Traf2 and Smad4 may play a role in the cross-talk between TNF-{alpha} and BMP signaling pathways.

  3. Synthesis and bioactivity of 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N-xylopyranosyl-1,3,4-oxa(thia)diazol-2-amines.

    PubMed

    He, Yao-Wu; Cao, Ling-Hua; Zhang, Jian-Bin; Wang, Duo-Zhi; Aisa, Haji Akber

    2011-04-01

    A series of new N'-[N-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)thiocarbamoyl]-2-[(1-aryl-1H-tetrazol-5-yl)sulfanyl]acetohydrazides 5a-5e were synthesized rapidly in high yields from 2-(1-aryl-1H-tetrazol-5-ylsulfanyl)acetohydrazides 3a-3e and 2,3,4-tri-O-acetyl-β-d-xylopyranosyl isothiocyanate 4, then 5a-5e were converted to a series of new 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-O-acetyl-β-D-xylopyranosyl)-1,3,4-oxadiazole-2-amines 6a-6e and 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-O-acetyl-β-D-xylopyranosyl)-1,3,4-thiadiazole-2-amines 7a-7e, respectively under mercuric acetate/alcohol system or acetic anhydride/phosphoric acid system, then deacetylated in the solution of CH(3)ONa/CH(3)OH. All of the novel compounds were characterized by IR, (1)H NMR, (13)C NMR, MS and elemental analysis. The structures of compounds 2e, 3e, 5a and 5c have been determined by X-ray diffraction analysis. Some of the synthesized compounds displayed PTP1B inhibition and microorganism inhibition. PMID:21353206

  4. Crystal structure of 2-[(3S,4S)-4-(anthracen-9-yl)-1-(4-meth­oxy­phen­yl)-2-oxoazetidin-3-yl]-2-aza-2H-phenalene-1,3-dione unknown solvate

    PubMed Central

    Çelik, Ísmail; Akkurt, Mehmet; Jarrahpour, Aliasghar; Rad, Javad Ameri; Çelik, Ömer

    2015-01-01

    The central β-lactam ring of the title compound, C36H24N2O4, is almost planar (r.m.s. deviation = 0.003 Å) and makes dihedral angles of 17.17 (19), 89.76 (17) and 78.44 (17)° with the benzene ring, the anthracene ring (r.m.s. deviation = 0.003 Å) and the 1H-benzo[de]iso­quinoline-1,3(2H)-dione moiety, which is nearly planar [maximum deviation = 0.098 (2) Å], respectively. The mol­ecular structure is stabilized by an intra­molecular C—H⋯N hydrogen bond. In the crystal, mol­ecules are linked via C—H⋯π and π–π stacking inter­actions [centroid–centroid distances = 3.5270 (19) and 3.779 (2) Å], forming a three-dimensional structure. A region of disordered electron density, probably disordered solvent mol­ecules, was treated with the SQUEEZE procedure in PLATON [Spek (2015 ▸). Acta Cryst. C71, 9–18], which indicated a solvent cavity of 322 Å3 containing approximately 91 electrons. Their formula mass and unit-cell characteristics were not taken into account during the refinement. PMID:25844239

  5. Crystal structure of 2-[(3S,4S)-4-(anthracen-9-yl)-1-(4-meth-oxy-phen-yl)-2-oxoazetidin-3-yl]-2-aza-2H-phenalene-1,3-dione unknown solvate.

    PubMed

    Çelik, Ísmail; Akkurt, Mehmet; Jarrahpour, Aliasghar; Rad, Javad Ameri; Çelik, Ömer

    2015-03-01

    The central β-lactam ring of the title compound, C36H24N2O4, is almost planar (r.m.s. deviation = 0.003 Å) and makes dihedral angles of 17.17 (19), 89.76 (17) and 78.44 (17)° with the benzene ring, the anthracene ring (r.m.s. deviation = 0.003 Å) and the 1H-benzo[de]iso-quinoline-1,3(2H)-dione moiety, which is nearly planar [maximum deviation = 0.098 (2) Å], respectively. The mol-ecular structure is stabilized by an intra-molecular C-H⋯N hydrogen bond. In the crystal, mol-ecules are linked via C-H⋯π and π-π stacking inter-actions [centroid-centroid distances = 3.5270 (19) and 3.779 (2) Å], forming a three-dimensional structure. A region of disordered electron density, probably disordered solvent mol-ecules, was treated with the SQUEEZE procedure in PLATON [Spek (2015 ▶). Acta Cryst. C71, 9-18], which indicated a solvent cavity of 322 Å(3) containing approximately 91 electrons. Their formula mass and unit-cell characteristics were not taken into account during the refinement. PMID:25844239

  6. Histone H3K27 trimethylation inhibits H3 binding and function of SET1-like H3K4 methyltransferase complexes.

    PubMed

    Kim, Dae-Hwan; Tang, Zhanyun; Shimada, Miho; Fierz, Beat; Houck-Loomis, Brian; Bar-Dagen, Maya; Lee, Seunghee; Lee, Soo-Kyung; Muir, Tom W; Roeder, Robert G; Lee, Jae W

    2013-12-01

    Trimethylated histone H3 lysine 4 (H3K4) and H3K27 generally mark transcriptionally active and repressive chromatins, respectively. In most cell types, these two modifications are mutually exclusive, and this segregation is crucial for the regulation of gene expression. However, how this anticorrelation is achieved has not been fully understood. Here, we show that removal of the H3K27 trimethyl mark facilitates recruitment of SET1-like H3K4 methyltransferase complexes to their target genes by eliciting a novel interaction between histone H3 and two common subunits, WDR5 and RBBP5, of SET1-like complexes. Consistent with this result, H3K27 trimethylation destabilizes interactions of H3 with SET1-like complexes and antagonizes their ability to carry out H3K4 trimethylation of peptide (H3 residues 1 to 36), histone octamer, and mononucleosome substrates. Altogether, our studies reveal that H3K27 trimethylation of histone H3 represses a previously unrecognized interaction between H3 and SET1-like complexes. This provides an important mechanism that directs the anticorrelation between H3K4 and H3K27 trimethylation. PMID:24126056

  7. A 1,4-diphenyl-1,2,3-triazole-based β-turn mimic constructed by click chemistry.

    PubMed

    Wu, Chun-Fang; Zhao, Xin; Lan, Wen-Xian; Cao, Chunyang; Liu, Jin-Tao; Jiang, Xi-Kui; Li, Zhan-Ting

    2012-05-01

    A series of 1,4-diphenyl-1,2,3-triazole-incorporated amide derivatives have been designed and prepared. X-ray crystallographic and (1D and 2D) (1)H NMR studies reveal that these compounds fold into stable U-shaped conformations driven by three-center intramolecular C-H···O hydrogen-bonding formed between the triazole C-5 H atom and the two ether O atoms. Such folded structures make this 1,4-diphenyl-1,2,3-triazole skeleton a good candidate to be used as β-turn mimic. To prove this, the formation of a β-hairpin structure induced by this β-turn motif has been further demonstrated.

  8. Suppression of Adipogenesis by 5-Hydroxy-3,6,7,8,3',4'-Hexamethoxyflavone from Orange Peel in 3T3-L1 Cells.

    PubMed

    Wang, Yu; Lee, Pei-Sheng; Chen, Yi-Fen; Ho, Chi-Tang; Pan, Min-Hsiung

    2016-09-01

    We reported previously that hydroxylated polymethoxyflavones (HPMFs) effectively suppressed obesity in high-fat-induced mouse. In this study, we further investigated the molecular mechanism of action of 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5-OH-HxMF), one of major HPMFs in orange peel. Treatment of 5-OH-HxMF effectively inhibited lipid accumulation by 55-60% in a dose-dependent manner. The 5-OH-HxMF attenuated adipogenesis through downregulating adipogenesis-related transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs), as well as downstream target fatty acid synthase and acetyl-CoA carboxylase (ACC). 5-OH-HxMF activated adenosine monophosphate-activated protein kinase signaling and silent mating type information regulation 1 (SIRTUIN 1 or SIRT1) in 3T3-L1 adipocytes to decrease lipid accumulation. In addition, the inhibition rate of lipid accumulation was compared between 5-OH-HxMF and 3,5,6,7,8,3',4'-heptamethoxyflavone (HpMF). 5-OH-HxMF inhibited lipid accumulation 15-20% more than HpMF did, indicating that hydroxyl group at position 5 can be a key factor in the suppression of adipogenesis. PMID:27542074

  9. Genetic Mapping at 3-Kilobase Resolution Reveals Inositol 1,4,5-Triphosphate Receptor 3 as a Risk Factor for Type 1 Diabetes in Sweden

    PubMed Central

    Roach, Jared C.; Deutsch, Kerry; Li, Sarah; Siegel, Andrew F.; Bekris, Lynn M.; Einhaus, Derek C.; Sheridan, Colleen M.; Glusman, Gustavo; Hood, Leroy; Lernmark, Åke; Janer, Marta

    2006-01-01

    We mapped the genetic influences for type 1 diabetes (T1D), using 2,360 single-nucleotide polymorphism (SNP) markers in the 4.4-Mb human major histocompatibility complex (MHC) locus and the adjacent 493 kb centromeric to the MHC, initially in a survey of 363 Swedish T1D cases and controls. We confirmed prior studies showing association with T1D in the MHC, most significantly near HLA-DR/DQ. In the region centromeric to the MHC, we identified a peak of association within the inositol 1,4,5-triphosphate receptor 3 gene (ITPR3; formerly IP3R3). The most significant single SNP in this region was at the center of the ITPR3 peak of association (P=1.7×10-4 for the survey study). For validation, we typed an additional 761 Swedish individuals. The P value for association computed from all 1,124 individuals was 1.30×10-6 (recessive odds ratio 2.5; 95% confidence interval [CI] 1.7–3.9). The estimated population-attributable risk of 21.6% (95% CI 10.0%–31.0%) suggests that variation within ITPR3 reflects an important contribution to T1D in Sweden. Two-locus regression analysis supports an influence of ITPR3 variation on T1D that is distinct from that of any MHC class II gene. PMID:16960798

  10. Novel 2- and 4- Substituted 1H-Imidazo[4,5-c]quinolin-4-amine Derivatives as Allosteric Modulators of the A3 Adenosine Receptor

    PubMed Central

    Kim, Yoonkyung; de Castro, Sonia; Gao, Zhan-Guo; IJzerman, Adriaan P.; Jacobson, Kenneth A.

    2009-01-01

    4-Arylamino and 2- cycloalkyl (including amino substitution) modifications were made in a series of 1H-imidazo-[4,5-c]quinolin-4-amine derivatives as allosteric modulators of the human A3 adenosine receptor (AR). In addition to allosteric modulation of the maximum functional efficacy (in [35S]GTPγS G protein binding assay) of the A3AR agonist Cl-IB-MECA (15), some analogues also weakly inhibited equilibrium radioligand binding at ARs. 4-(3,5-Dichlorophenylamino) (6) or 2-(1-adamantyl) (20) substitution produced allosteric enhancement (twice the maximal agonist efficacy), with minimal inhibition of orthosteric AR binding. 2-(4-Tetrahydropyranyl) substitution abolished allosteric enhancement but preserved inhibition of orthosteric binding. Introduction of nitrogen in the six-membered ring at 2 position, to improve aqueous solubility and provide a derivatization site, greatly reduced the allosteric enhancement. 2-(4-(Benzoylamino)cyclohexyl) analogues 23 and 24 were weak negative A3AR modulators. Thus, consistent with previous findings, the allosteric and orthosteric inhibitory A3AR effects in imidazoquinolines are structurally separable, suggesting the possible design of additional derivatives with enhanced positive or negative allosteric A3AR activity and improved selectivity in comparison to inhibition of orthosteric binding. PMID:19284749

  11. Synthesis, crystal structure determination and antiproliferative activity of novel 2-amino-4-aryl-4,10-dihydro[1,3,5]triazino[1,2- a]benzimidazoles

    NASA Astrophysics Data System (ADS)

    Hranjec, Marijana; Pavlović, Gordana; Karminski-Zamola, Grace

    2012-01-01

    This manuscript describes the synthesis of novel 2-amino-4-aryl-4,10-dihydro-[1,3,5]triazino[1,2- a]benzimidazoles as hydrochloride salts 4a-n and 5b which were prepared in the reaction of cyclocondensation between 2-guanidinobenzimidazole and versatile heteroaromatic aldehydes. Structures of all prepared compounds have been studied by using 1H and 13C NMR, IR and UV/Vis spectroscopy. The crystal and molecular structure of 4f was determined by X-ray diffraction on single crystals. The molecule of 2-amino-4-(4'-methylphenyl)-4,10-dihydro[1,3,5]triazino[1,2- a]benzimidazole hydrochloride 4f (C 16H 16N 5+·Cl -) exists in the solid state in one of the possible tautomeric forms, being protonated at the one of the nitrogen atoms of the 1,4-dihydrotriazine ring. The molecule is highly delocalized within the 4,10-dihydro[1,3,5]triazino[1,2- a]benzimidazole moiety with the highest deviation from the plane for the methine carbon atom and the protonated nitrogen atom of the 1,4-dihydrotriazine ring. The cations are joined via N-H⋯N hydrogen bonds into R22(8) centrosymmetric dimers. Cation dimers are further connected with Cl - ions via N-H⋯Cl and C-H⋯Cl hydrogen bonds into 2D chains spreading along the b axis. The obtained single-crystal X-ray structure determination unequivocally confirms tautomeric form of the compound present in the solid-state and can represent tantative pattern for other prepared compounds. All prepared compounds were tested on their antiproliferative activity in vitro on several human cancer cell lines. Compound 4m was the most active one (IC 50 ≈ 20 μM), while compounds 4d, 4f, 4k, 4l4m showed moderate, but non-selective, antiproliferative activity with IC 50 25-60 μM.

  12. Functional analysis of {alpha}1,3/4-fucosyltransferase VI in human hepatocellular carcinoma cells

    SciTech Connect

    Guo, Qiya; Guo, Bin; Wang, Yingming; Wu, Jun; Jiang, Wenjun; Zhao, Shenan; Qiao, Shouyi; Wu, Yanhua

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Human FUT6 is up-regulated in HCC tissues. Black-Right-Pointing-Pointer Expression of FUT6 promotes G0/G1-S transition and cell growth. Black-Right-Pointing-Pointer FUT6 confers a growth advantage in vivo. Black-Right-Pointing-Pointer FUT6 suppresses p21 expression through modulating PI3K/Akt signaling. -- Abstract: The {alpha}1,3/4-fucosyltransferases (FUT) subfamily are key enzymes in cell surface antigen synthesis during various biological processes. A novel role of FUTs in tumorigenesis has been discovered recently, however, the underlying mechanism remains largely unknown. Here, we characterized FUT6, a member of {alpha}1,3/4-FUT subfamily, in human hepatocellular carcinoma (HCC). In HCC tissues, the expression levels of FUT6 and its catalytic product SLe{sup x} were significantly up-regulated. Overexpression of FUT6 in HCC cells enhanced S-phase cell population, promoted cell growth and colony formation ability. Moreover, subcutaneously injection of FUT6-overexpressing cells in nude mice promoted cell growth in vivo. In addition, elevating FUT6 expression markedly induced intracellular Akt phosphorylation, and suppressed the expression of the cyclin-dependent kinases inhibitor p21. Bath application of the PI3K inhibitor blocked FUT6-induced Akt phosphorylation, p21 suppression and cell proliferation. Our results suggest that FUT6 plays an important role in HCC growth by regulating the PI3K/Akt signaling pathway.

  13. Synthesis and anti-HIV-1 screening of novel N'-(1-(aryl)ethylidene)-2-(5,5-dioxido-3-phenylbenzo[e]pyrazolo[4,3-c][1,2]thiazin-4(1H)-yl)acetohydrazides.

    PubMed

    Aslam, Sana; Ahmad, Matloob; Zia-Ur-Rehman, Muhammad; Montero, Catherine; Detorio, Mervi; Parvez, Masood; Schinazi, Raymond F

    2014-11-01

    A novel series of N'-(1-(aryl)ethylidene)-2-(5,5-dioxido-3-phenylbenzo[e]pyrazolo[4,3-c][1,2]thiazin-4(1H)-yl)acetohydrazides was synthesized. The synthesis was carried out by thermal method as well as ultrasonic bath to reduce reaction time and to enhance product yields. The synthesized compounds were characterized by spectroscopic techniques like NMR, infrared and EIMS. The structure of compound 5w was elucidated by X-ray crystallography. The titled compounds were evaluated for anti-human immunodeficiency virus type 1 (anti-HIV-1) and cytotoxic activities. Biological studies indicated that amongst these compounds, 5a, b, j, h and i showed the activity with median effective concentration (EC50) values less than 20 μM. Compound 5i exhibited the most potent anti-HIV-1 activity (EC50 = 3.2 μM) while 5h showed anti-HIV-1 activity (EC50 = 3.8 μM) with no toxicity at all in primary human lymphocytes, CEM and VERO cells.

  14. Electrochemical performance and 7Li NMR studies on an inverse spinel LiNi 1/3Co 1/3Mn 1/3VO 4 for Li-ion batteries

    NASA Astrophysics Data System (ADS)

    Fey, George Ting-Kuo; Muralidharan, P.; Cho, Yung-Da; Chang, Pai-Ching; Kao, Hsien-Ming

    A new inverse spinel LiNi 1/3Co 1/3Mn 1/3VO 4 cathode material was synthesized through a citric acid assisted polyethylene glycol (CA:PEG; 3:1, 3:0.5 and 3:0) polymeric method, followed by calcination at 723 K for 5 h in air. The synthesized compound was characterized by TG/DTGA, XRD, FTIR, TEM, and 7Li NMR techniques. TG/DTGA curves showed that the formation of LiNi 1/3Co 1/3Mn 1/3VO 4 occurred between 523 and 673 K and the phase pure crystalline formed at 723 K, as also confirmed by XRD analysis which showed that the crystalline phase peaks formed when heated at 723 K for 5 h in air. TEM images revealed that nanosized particles ranged ∼170-190 nm. FTIR spectra showed that all organic residues were removed and LiNi 1/3Co 1/3Mn 1/3VO 4 formed. The 7Li MAS NMR spectrum of the LiNi 1/3Co 1/3Mn 1/3VO 4 sample revealed that the paramagnetic effect is small and small side band manifolds were observed. The galvanostatic cycling study suggests that the cycle stability and capacity retention were enhanced for LiNi 1/3Co 1/3Mn 1/3VO 4 prepared with a CA:PEG molar ratio of 3:1 when it was cycled between 2.8 and 4.9 V (versus Li) at a 0.15 C rate. The electrochemical impedance behavior suggested that a passive layer was formed on the surface of the cathode materials during continuous cycling.

  15. The polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthaline lacks liver tumor initiating and promoting activity in rats exposed to human-relevant doses.

    PubMed

    Steinberg, P; Zschaler, I; Thom, E; Kuna, M; Wüst, G; Schäfer-Schwebel, A; Müller, R; Kramer, P J; Weisse, G

    2001-11-01

    7-Acetyl-1,1,3,4,4,6-hexamethyl- 1,2,3,4-tetra-hydronaphthaline (AHTN) is one of the two most widely used fragrances of a group of substances known collectively as the polycyclic musks. In the last few years evidence has been accumulating that AHTN is hepatotoxic when administered at high doses. In the present study the subchronic hepatotoxicity of AHTN administered to rats at doses within the human exposure range was evaluated. For this purpose female and male juvenile Wistar rats were exposed to AHTN (300 microg/kg body weight per day, i.p.) alone or to a single dose of diethylnitrosamine (DEN) (100 mg/kg body weight, i.p.) followed by AHTN (1, 10, 100 or 300 microg/kg body weight per day, i.p.) for 90 days. Thereafter the liver architecture as well as the presence of placental glutathione S-transferase (GST-P)-positive hepatic lesions was assessed. In male animals receiving AHTN alone or in combination with DEN the number of GST-P-positive single hepatocytes was similar to that in untreated rats, while GST-P-positive mini-foci and foci were not observed. In the case of female rats the number of GST-P-positive single hepatocytes and mini-foci in AHTN-treated rats was similar to that in untreated animals, whereas in those animals receiving AHTN either alone or in combination with DEN, GST-P-positive foci could not be detected or were present in a number as similar to that in untreated rats. In conclusion, in the present study it has been shown that AHTN administered over a 90-day period in concentrations similar to those taken up daily by humans does not lead to hepatotoxicity.

  16. Relative frequencies of rotavirus serotypes 1, 2, 3, and 4 in Venezuelan infants with gastroenteritis.

    PubMed Central

    Flores, J; Taniguchi, K; Green, K; Perez-Schael, I; Garcia, D; Sears, J; Urasawa, S; Kapikian, A Z

    1988-01-01

    We have used a recently developed monoclonal antibody enzyme-linked immunosorbent assay (K. Taniguchi, T. Urasawa, Y. Morita, H. B. Greenberg, and S. Urasawa, J. Infect. Dis. 155:1159-1166, 1987) for serotyping rotaviruses recovered from 134 Venezuelan infants over a period of 15 months. One hundred and nine of the specimens were typed with the following distribution: serotype 1, 48%; serotype 2, 16%; serotype 3, 22%; and serotype 4, 14%. Three specimens reacted with two different monoclonal antibodies. In addition, 6 specimens (5%) containing enough outer capsid antigen could not be typed; partial RNA sequence analysis of the glycoprotein gene from three of these six strains failed to reveal sequence differences with prototype strains that could be serotyped with the monoclonal antibodies. Variations in the recovery rates of the different serotypes were observed. Serotypes 2, 3, and 4 predominated at the beginning of the study, and serotype 1 predominated at the end of the study. Diarrheal illness appeared to be more prolonged in infants shedding rotavirus serotypes 1 and 3 than in those shedding serotypes 2 and 4. PMID:2846637

  17. Fragrance material review on 2-hydroxy-3,4-dimethyl-2-cyclopenten-1-one.

    PubMed

    Scognamiglio, J; Jones, L; Letizia, C S; Api, A M

    2012-10-01

    A toxicologic and dermatologic review of 2-hydroxy-3,4-dimethyl-2-cyclopenten-1-one when used as a fragrance ingredient is presented. 2-Hydroxy-3,4-dimethyl-2-cyclopenten-1-one is a member of the fragrance structural group Ketones Cyclopentanones and Cyclopentenones. The common characteristic structural element of the group members is a cyclopentanone or cyclopentenone ring with a straight or branched chain alkane or alkene substituent. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 2-hydroxy-3,4-dimethyl-2-cyclopenten-1-one were evaluated, then summarized and includes physical properties data. A safety assessment of the entire Ketones Cyclopentanones and Cyclopentenones will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Ketones Cyclopentanones and Cyclopentenones in fragrances.

  18. VizieR Online Data Catalog: ATLAS 1.4GHz Data Release 3 (Franzen+, 2015)

    NASA Astrophysics Data System (ADS)

    Franzen, T. M. O.; Banfield, J. K.; Hales, C. A.; Hopkins, A.; Norris, R. P.; Seymour, N.; Chow, K. E.; Herzog, A.; Huynh, M. T.; Lenc, E.; Mao, M. Y.; Middelberg, E.

    2016-04-01

    ATLAS covers two regions, each of ~3 deg2, surroundin (RA=03:30:16.3, DE=-28:05:12.4) and ELAIS-S1 (RA=00:33:50.8, DE=-43:44:57.4). These two fields have previously been observed at 1.4GHz as part of the ATLAS project and are described by Hales et al. (2014, Cat. J/MNRAS/441/2555). Both of these fields were originally targeted for radio observations as they overlap with SWIRE which includes infrared and optical data for the majority of the radio objects. ATCA project C1967 was allocated 1000h distributed over 78d between 2009 June and 2010 June to extend ATLAS. Previous ATLAS DR2 observations (ATCA Project IDs C1035 and C1241) from Hales et al. (2014, Cat. J/MNRAS/441/2555) were combined with our CABB observations to maximize the sensitivity. The data were combined in the image plane for reasons related to bandwidth smearing, and described in detail in Section 3.2. These data consist of two 128MHz bands centred at 1344 and 1432MHz each containing 16 channels of 8MHz in size. Both bands were imaged together using a similar procedure to the CABB data. (1 data file).

  19. Substituent effect on photophysical properties of bi-1,3,4-oxadiazole derivatives in solution

    NASA Astrophysics Data System (ADS)

    Chen, Fangyi; Tian, Taiji; Zhao, Chengxiao; Bai, Binglian; Li, Min; Wang, Haitao

    2016-04-01

    A series of phenyl substituted bi-1,3,4-oxadiazole derivatives were designed and synthesized; the effect of substituent on the photophysical properties and molecular electronic structures was fully studied by the combination of experimental techniques and theoretical calculations. Compared to parent compound without any substituent (BOXD), fluoro-substituent shows little effect on the absorption and emission spectra, whilst a little larger spectral red-shift could be observed for methoxy-, nitro-substituted derivatives and thienyl-substituted bi-1,3,4-oxadiazole (TBOXD). These spectral changes can be well explained by theoretically calculated HOMO and LUMO energy level changes. All these molecules show high fluorescence quantum yield except for nitro-substituted derivative in dilute solutions. The quantum yield of BOXD changes with the concentration and exhibits a high value at the concentrated solution. This work revealed the influence of substituent on the photophysical properties of bi-1,3,4-oxadizaole derivatives in dilute solutions and provided guidance for designing molecules with potential application.

  20. Synthesis and Characterization of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Propoxybenzoates and Their Hydrochloride Salts.

    PubMed

    Marvanova, Pavlina; Padrtova, Tereza; Pekarek, Tomas; Brus, Jiri; Czernek, Jiri; Mokry, Petr; Humpa, Otakar; Oravec, Michal; Jampilek, Josef

    2016-01-01

    Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by means of (13)C-CP/MAS and (15)N-CP/MAS NMR and IR spectroscopy. Using these solid-state analytical techniques, it was found that both nitrogen atoms were protonated when excess hydrogen chloride was used for preparation of salts. On the other hand, when the equimolar amount of hydrogen chloride was used, piperazine nitrogen substituted by aryl was protonated. PMID:27258242