- 2-(Halogenated Phenyl) acetamides and propanamides as potent TRPV1 antagonists
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A series consisting of 117 2-(halogenated phenyl) acetamide and propanamide analogs were investigated as TRPV1 antagonists. The structure–activity analysis targeting their three pharmacophoric regions indicated that halogenated phenyl A-region analogs exhibited a broad functional profile ranging from agonism to antagonism. Among the compounds, antagonists 28 and 92 exhibited potent antagonism toward capsaicin for hTRPV1 with Ki[CAP] = 2.6 and 6.9 nM, respectively. Further, antagonist 92 displayed promising analgesic activity in vivo in both phases of the formalin mouse pain model. A molecular modeling study of 92 indicated that the two fluoro groups in the A-region made hydrophobic interactions with the receptor.
- Ann, Jihyae,Bahrenberg, Gregor,Blumberg, Peter M.,Choi, Sun,Christoph, Thomas,Do, Nayeon,Frank-Foltyn, Robert,Ha, Heejin,Jeong, Jin Ju,Kang, Jin Mi,Kim, Changhoon,Kwon, Sun Ok,Lee, Jeewoo,Lee, Sunho,Lesch, Bernhard,Stockhausen, Hannelore,Vu, Thi Ngoc Lan,Yoon, Sanghee
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- Rapid Assembly of Saturated Nitrogen Heterocycles in One-Pot: Diazo-Heterocycle “Stitching” by N–H Insertion and Cyclization
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Methods that provide rapid access to new heterocyclic structures in biologically relevant chemical space provide important opportunities in drug discovery. Here, a strategy is described for the preparation of 2,2-disubstituted azetidines, pyrrolidines, pi
- Boddy, Alexander J.,Affron, Dominic P.,Cordier, Christopher J.,Rivers, Emma L.,Spivey, Alan C.,Bull, James A.
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supporting information
p. 1458 - 1462
(2019/01/04)
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- Synthesis & characterization of 2-(substituted-phenyl)acetohydrazide analogs, 1,3,4-oxadiazoles, and 1,2,4-triazine Ring Systems: A novel class of potential analgesic and anti-inflammatory agents
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The new series of 2-(substituted-phenyl)acetohydrazides analogs, S-alkylated 5-substituted-1,3,4-oxadiazoles-2-thione derivatives and 5-arylidene-3-substituted-1,2,4-triazines have been synthesized in good yields and characterized by IR, NMR, mass spectral and elemental analyses. All the synthesized compounds 4(a-d), 5(a-d), 7(a-b), and 8(a-f) are evaluated for their in vitro DPPH scavenging, antimicrobial activity, in vivo analgesic, anti-inflammatory activities. The results of the anti-inflammatory activity are supported by molecular docking study with mouse COX-1 (PDB ID: 2CZT) and COX-2 (PDB ID: 3LN1) enzymes to predict their putative interactions. Among all the assays conducted, the compounds 5-(4-bromophenyl)-3-(naphthalen-2-ylmethyl)-1,2,4-triazine (4d) and2-{[5-(diphenylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}-N-(pyrazin-2-yl)acetamide (8a) have emerged as the most potent molecules.
- Nayak, Prakash S.,Narayana, Badiadka,Fernandes, Jennifer,Sarojini, Balladka K.,Sheik, Sana,Shashidhara, Kenkere S.,Chandrashekhar, Konambi R.,Byrappa, Kullaiah
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p. 547 - 562
(2016/10/12)
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- USE OF AMITIFADINE, (+)-1-(3,4-DICHLOROPHENYL)-3-AZABICYCLO[3.1.0]HEXANE IN METHODS AND COMPOSITIONS WITH ENHANCED EFFICACY AND REDUCED METABOLIC SIDE EFFECTS AND TOXICITY FOR TREATMENT OF DEPRESSION AND OTHER CENTRAL NERVOUS SYSTEM DISORDERS AND CONDITIO
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The present invention relates to (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and pharmaceutically acceptable active salts, polymorphs, glycosylated derivatives, metabolites, solvates, hydrates, and/or prodrugs of (+)-1-(3,4-dichlorophenyl)-3-azab
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Paragraph 0162
(2016/12/22)
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- Synthesis of α-aryl esters and nitriles: Deaminative coupling of α-aminoesters and α-aminoacetonitriles with arylboronic acids
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Transition-metal-free synthesis of α-aryl esters and nitriles using arylboronic acids with α-aminoesters and α-aminoacetonitriles, respectively, as the starting materials has been developed. The reaction represents a rare case of converting C(sp3)-N bonds into C(sp3)-C(sp2) bonds. The reaction conditions are mild, demonstrate good functional-group tolerance, and can be scaled up. Touch base: A transition-metal-free protocol for the synthesis of α-aryl esters and nitriles by deaminative coupling is presented. Strong bases and transition-metal catalysts are not needed. The new synthetic method uses readily available starting materials and demonstrates wide substrate scope.
- Wu, Guojiao,Deng, Yifan,Wu, Chaoqiang,Zhang, Yan,Wang, Jianbo
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supporting information
p. 10510 - 10514
(2016/02/18)
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- PREPARATION AND USE OF (+)-1-(3,4-DICHLOROPHENYL)-3-AZABICYCLO[3.1.0]HEXANE IN THE TREATMENT OF CONDITIONS AFFECTED BY MONOAMINE NEUROTRANSMITTERS
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The present invention relates to (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and pharmaceutically acceptable active salts, polymorphs, glycosylated derivatives, metabolites, solvates, hydrates, and/or prodrugs of (+)-1-(3,4-dichlorophenyl)-3-azab
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Page/Page column 61-62
(2012/06/16)
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- Discovery, structure-activity relationships, pharmacokinetics, and efficacy of glucokinase activator (2 R)-3-cyclopentyl-2-(4-methanesulfonylphenyl)-N- thiazol-2-yl-propionamide (RO0281675)
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Glucokinase (GK) is a glucose sensor that couples glucose metabolism to insulin release. The important role of GK in maintaining glucose homeostasis is illustrated in patients with GK mutations. In this publication, identification of the hit molecule 1 and its SAR development, which led to the discovery of potent allosteric GK activators 9a and 21a, is described. Compound 21a (RO0281675) was used to validate the clinical relevance of targeting GK to treat type 2 diabetes.
- Haynes, Nancy-Ellen,Corbett, Wendy L.,Bizzarro, Fred T.,Guertin, Kevin R.,Hilliard, Darryl W.,Holland, George W.,Kester, Robert F.,Mahaney, Paige E.,Qi, Lida,Spence, Cheryl L.,Tengi, John,Dvorozniak, Mark T.,Railkar, Aruna,Matschinsky, Franz M.,Grippo, Joseph F.,Grimsby, Joseph,Sarabu, Ramakanth
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supporting information; experimental part
p. 3618 - 3625
(2010/07/05)
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- 1,2-disubstituted-6-oxo-3-phenyl-piperidine-3-carboxamides and combinatorial libraries thereof
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The invention relates to combinatorial libraries containing two or more novel piperidine-3-carboxamide derivative compounds, methods of preparing the piperidine-3-carboxamide derivative compounds and piperidine-3-carboxamide derivative compounds bound to a resin
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- Process for producing novel naphthyridine derivatives
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A novel naphthyridine derivative showing high activity as a tachykinin receptor antagonist can be produced at high efficiency by reacting an acylating agent such as a carboxylic acid derivative with a compound represented by the formula (1): wherein R1, R2 and R3 represent independently a hydrogen atom, a lower alkyl group, a lower alkoxyl group, an aryl group, a heteroaryl group, an amino group, etc., and X1 and X2 represent respectively a halogen atom.
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- Cyclic amide derivatives for treating asthma
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Compounds of formula I STR1 wherein Q1, Q2, Q3, and Q4 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.
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- Reactions of cationic (η6-chloroarene) complexes of iron and ruthenium with some O-silyl and C-silyl compounds
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The introduction of an alylcarbonyl side chain into the aromatic ring of some chloro-substituted benzenes has been achieved under mild conditions by the Yanovsky-type reaction of (η6-chloroarene)(η5-cyclopentadienyl) cationic complex
- Cambie, Richard C.,Coulson, Sally A.,Mackay, Lindsey G.,Janssen, Sally J.,Rutledge, Peter S.,Woodgate, Paul D.
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p. 385 - 409
(2007/10/02)
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- Electrochemistry of some Ethyl α-Bromo(Dihalophenyl) Acetates and Electrochemical Synthesis of Diastereoisomeric Diethyl 2,3-Bis(dihalogenophenyl)Succinates
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Ethyl α-bromo-2,4- or -3,4-dihalogenophenylacetates (ABr), where halogen = F or Cl, are prepared and electrolysed on reticulated vitreous carbon (RVC) in dimethylformamide containing Et4NClO4 (0.1 mol dm-3).Potentiostatic reduction at E = -1.6 to -1.8 V versus SCE furnishes the corresponding racemic and meso succinates (AA) (13)-(16).Monoesters AH (5)-(8) are also isolated.An excess of racemic isomer is observed for (14), (15), and (16).Voltammetric experiments show practically no difference between the reduction potentials of the isomeric compounds.Diastereoisomers can be distinguished by NMR spectroscopy, allowing diastereoisomeric excess (de) to be evaluated before isolation of the single products.A mechanism involving radical intermediates A* cannot be excluded.On this basis, the des can be explained by assuming different geometries for A* when the phenyl group bears different substituents.
- Mattiello, Leonardo,Luca, Carlo De,Rampazzo, Liliana
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p. 1041 - 1044
(2007/10/02)
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- Method of treating depression using azabicyclohexanes
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The present invention concerns certain novel substituted 3-azabicyclo[3.1.0]hexanes and a method of treating depression and stress in a warm-blooded animal, comprising the administration of substituted 3-azabicyclo[3.1.0]hexanes.
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- Azabicyclohexanes
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Substituted 3-azabicyclo[3.1.0]hexanes, acid addition salts, method of use and method of preparation are described. The compounds have anxiolytic and analgesic activity.
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