Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1358889 | Bioorganic & Medicinal Chemistry Letters | 2015 | 5 Pages |
Abstract
A series of α-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 α-m-tolyl substituent, showed highly potent and selective antagonism of capsaicin with Ki(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.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Phuong-Thao Tran, Ho Shin Kim, Jihyae Ann, Sung-Eun Kim, Changhoon Kim, Mannkyu Hong, Van-Hai Hoang, Van T.H. Ngo, Sunhye Hong, Minghua Cui, Sun Choi, Peter M. Blumberg, Robert Frank-Foltyn, Gregor Bahrenberg, Hannelore Stockhausen, Thomas Christoph,