Α-Substituted 2-(3-fluoro-4-methylsulfonamidophenyl)acetamides as potent TRPV1 antagonists. Issue 11 (1st June 2015)

• Record Type: Journal Article
• Authors: Tran, Phuong-Thao; Kim, Ho Shin; Ann, Jihyae; Kim, Sung-Eun; Kim, Changhoon; Hong, Mannkyu; Hoang, Van-Hai; Ngo, Van T.H.; Hong, Sunhye; Cui, Minghua; Choi, Sun; Blumberg, Peter M.; Frank-Foltyn, Robert; Bahrenberg, Gregor; Stockhausen, Hannelore; Christoph, Thomas; Lee, Jeewoo
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 11(2015)
• Page Start: 2326
• Page End: 2330
• Publication Date: 2015-06-01
• Subjects: TRPV1 antagonist -- Analgesic -- Capsaicin -- Molecular modeling; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.04.024
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 h TRPV1 activation by capsaicin. Compound34, which possesses an α- 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 parent1 . Docking analysis using our homology model indicated that the high potency of34 might be attributed to a specific hydrophobic interaction of the m -tolyl group with the receptor.