- Discovery, synthesis and characterization of a series of (1-alkyl-3-methyl-1H-pyrazol-5-yl)-2-(5-aryl-2H-tetrazol-2-yl)acetamides as novel GIRK1/2 potassium channel activators
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The present study describes the discovery and characterization of a series of 5-aryl-2H-tetrazol-3-ylacetamides as G protein-gated inwardly-rectifying potassium (GIRK) channels activators. Working from an initial hit discovered during a high-throughput screening campaign, we identified a tetrazole scaffold that shifts away from the previously reported urea-based scaffolds while remaining effective GIRK1/2 channel activators. In addition, we evaluated the compounds in Tier 1 DMPK assays and have identified a (3-methyl-1H-pyrazol-1-yl)tetrahydrothiophene-1,1-dioxide head group that imparts interesting and unexpected microsomal stability compared to previously-reported pyrazole head groups.
- Sharma, Swagat,Kozek, Krystian A.,Abney, Kristopher K.,Kumar, Sushil,Gautam, Nagsen,Alnouti, Yazen,David Weaver,Hopkins, Corey R.
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supporting information
p. 791 - 796
(2019/02/06)
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- Synthesis, antimicrobial and antioxidant activities of imidazotriazoles and new multicomponent reaction toward 5-amino-1-phenyl[1,2,4]triazole derivatives
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The Groebke-type multicomponent reaction between 5-amino-1,2,4-triazole derivatives, aromatic aldehydes and isocyanides has been studied from the viewpoint of convenient generation of combinatorial arrays of imidazo[2,1-c][1,2,4]triazoles. The reaction is
- Aouali, Monia,Mhalla, Dhekra,Allouche, Fatma,El Kaim, Laurent,Tounsi, Slim,Trigui, Mohamed,Chabchoub, Fakher
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p. 2732 - 2741
(2015/02/19)
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- PYRROLIDINYL UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS
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Compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts, or solvates or prodrugs thereof, where R1, R2, Ra, Rb, Rc, Rd, X, Ring B, and Ring C are as defined herein, and wherein Ring B moiety and the NH-C(=X)-NH moiety are in the trans configuration, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis and pelvic pain syndrome.
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Paragraph 00662
(2014/06/11)
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