alpha-Substituted 2-(3-fluoro-4-methylsulfonamidophenyl)acetamides as potent TRPV1 antagonists
- 주제(키워드) TRPV1 antagonist , Analgesic , Capsaicin , Molecular modeling
- 등재 SCIE, SCOPUS
- 발행기관 PERGAMON-ELSEVIER SCIENCE LTD
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000115659
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.bmcl.2015.04.024
초록/요약
A series of alpha-substituted acetamide derivatives of previously reported 2-(3-fluoro-4-methylsulfonamidophenyl) propanamide leads (1, 2) were investigated for antagonism of hTRPV1 activation by capsaicin. Compound 34, which possesses an alpha-m-tolyl substituent, showed highly potent and selective antagonism of capsaicin with K-i(CAP) = 0.1 nM. It thus reflected a 3-fold improvement in potency over parent 1. Docking analysis using our homology model indicated that the high potency of 34 might be attributed to a specific hydrophobic interaction of the m-tolyl group with the receptor. (C) 2015 Elsevier Ltd. All rights reserved.
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