Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: α-Substituted 2-(3-fluoro-4-methylsulfonamidophenyl)acetamides as potent TRPV1 antagonists.

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, Jeewoo Lee

Journal, date & volume: Bioorg. Med. Chem. Lett., 2015 Jun 1 , 25, 2326-30

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25937016

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.