6,6-Fused heterocyclic ureas as highly potent TRPV1 antagonists
- 주제(키워드) Analgesic , Molecular modeling , TRPV1 antagonist , Vanilloid receptor 1
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier Ltd
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000114155
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.bmcl.2014.12.086
초록/요약
A series of N-[{2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-pyridin-3-yl}methyl] N'-(6,6-fused heterocyclic) ureas have been investigated as hTRPV1 antagonists. Among them, compound 15 showed highly potent TRPV1 antagonism to capsaicin, with K i(ant) =0.2nM, as well as antagonism to other activators, and it was efficacious in a pain model. A docking study of 15 with our hTRPV1 homology model indicates that there is crucial hydrogen bonding between the ring nitrogen and the receptor, contributing to its potency.
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