Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: 2-Alkyl/alkenyl substituted pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as highly potent TRPV1 antagonists.

Authors: HyungChul Ryu, Sejin Seo, Seong-Hee Cho, Ho Shin Kim, Aeran Jung, Dong Wook Kang, Karam Son, Minghua Cui, Sun-hye Hong, Pankaz Kumar Sharma, Sun Choi, Peter M Blumberg, Robert Frank-Foltyn, Gregor Bahrenberg, Hannelore Stockhausen, Klaus Schiene, Thomas Christoph, Sven Frormann, Jeewoo Lee

Journal, date & volume: Bioorg. Med. Chem. Lett., 2014 Aug 15 , 24, 4039-43

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24948568

Abstract
A series of 2-alkyl/alkenyl pyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Multiple compounds showed excellent and stereospecific TRPV1 antagonism with better potency than previous lead 2. Among them, compound 15f demonstrated a strong analgesic profile in a rat neuropathic pain model and blocked capsaicin-induced hypothermia in a dose-dependent manner. Docking analysis of (S)-15f with our hTRPV1 homology model provided insight into its specific binding mode.