DSpace at EWHA: α-Substituted 2-(3-fluoro-4-methylsulfonamidophenyl)acetamides as potent TRPV1 antagonists

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

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

Authors: Tran P.-T.; Kim H.S.; Ann J.; Kim S.-E.; Kim C.; Hong M.; Hoang V.-H.; Ngo V.T.H.; Hong S.; Cui M.; Choi S.; Blumberg P.M.; Frank-Foltyn R.; Bahrenberg G.; Stockhausen H.; Christoph T.; Lee J.

Citation: Bioorganic and Medicinal Chemistry Letters vol. 25, no. 11, pp. 2326 - 2330

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 K<inf>i(CAP)</inf> = 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. © 2015 Elsevier Ltd. All rights reserved.