Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 최선 | * |
dc.date.accessioned | 2016-08-28T10:08:53Z | - |
dc.date.available | 2016-08-28T10:08:53Z | - |
dc.date.issued | 2012 | * |
dc.identifier.issn | 0022-2623 | * |
dc.identifier.other | OAK-9294 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/223076 | - |
dc.description.abstract | A series of N-(2-amino-6-trifluoromethylpyridin-3-ylmethyl)-2-(3-fluoro-4- methylsulfonylaminophenyl)propanamides were designed combining previously identified pharmacophoric elements and evaluated as hTRPV1 antagonists. The SAR analysis indicated that specific hydrophobic interactions of the 2-amino substituents in the C-region of the ligand were critical for high hTRPV1 binding potency. In particular, compound 49S was an excellent TRPV1 antagonist (K i(CAP) = 0.2 nM; IC50(pH) = 6.3 nM) and was thus approximately 100- and 20-fold more potent, respectively, than the parent compounds 2 and 3 for capsaicin antagonism. Furthermore, it demonstrated strong analgesic activity in the rat neuropathic model superior to 2 with almost no side effects. Compound 49S antagonized capsaicin induced hypothermia in mice but showed TRPV1-related hyperthermia. The basis for the high potency of 49S compared to 2 is suggested by docking analysis with our hTRPV1 homology model in which the 4-methylpiperidinyl group in the C-region of 49S made additional hydrophobic interactions with the hydrophobic region. © 2012 American Chemical Society. | * |
dc.language | English | * |
dc.title | 2-(3-Fluoro-4-methylsulfonylaminophenyl)propanamides as potent transient receptor potential vanilloid 1 (TRPV1) antagonists: Structure-activity relationships of 2-amino derivatives in the N-(6-trifluoromethylpyridin-3- ylmethyl) C-region | * |
dc.type | Article | * |
dc.relation.issue | 19 | * |
dc.relation.volume | 55 | * |
dc.relation.index | SCI | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 8392 | * |
dc.relation.lastpage | 8408 | * |
dc.relation.journaltitle | Journal of Medicinal Chemistry | * |
dc.identifier.doi | 10.1021/jm300780p | * |
dc.identifier.wosid | WOS:000309643500017 | * |
dc.identifier.scopusid | 2-s2.0-84867340601 | * |
dc.author.google | Kim M.S. | * |
dc.author.google | Ryu H. | * |
dc.author.google | Kang D.W. | * |
dc.author.google | Cho S.-H. | * |
dc.author.google | Seo S. | * |
dc.author.google | Park Y.S. | * |
dc.author.google | Kim M.-Y. | * |
dc.author.google | Kwak E.J. | * |
dc.author.google | Kim Y.S. | * |
dc.author.google | Bhondwe R.S. | * |
dc.author.google | Kim H.S. | * |
dc.author.google | Park S.-G. | * |
dc.author.google | Son K. | * |
dc.author.google | Choi S. | * |
dc.author.google | Deandrea-Lazarus I.A. | * |
dc.author.google | Pearce L.V. | * |
dc.author.google | Blumberg P.M. | * |
dc.author.google | Frank R. | * |
dc.author.google | Bahrenberg G. | * |
dc.author.google | Stockhausen H. | * |
dc.author.google | Kogel B.Y. | * |
dc.author.google | Schiene K. | * |
dc.author.google | Christoph T. | * |
dc.author.google | Lee J. | * |
dc.contributor.scopusid | 최선(8659831000) | * |
dc.date.modifydate | 20240305081003 | * |