Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: 6,6-Fused heterocyclic ureas as highly potent TRPV1 antagonists.

Authors: Wei Sun, Hyo-shin Kim, Sunho Lee, Aeran Jung, Sung-Eun Kim, Jihyae Ann, Suyoung Yoon, Sun Choi, Jin Hee Lee, Peter M Blumberg, Robert Frank-Foltyn, Gregor Bahrenberg, Klaus Schiene, Hannelore Stockhausen, Thomas Christoph, Sven Frormann, Jeewoo Lee

Journal, date & volume: Bioorg. Med. Chem. Lett., 2015 Feb 15 , 25, 803-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25597011

Abstract
A series of N-[{2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-pyridin-3-yl}methyl] N'-(6,6-fused heterocyclic) ureas have been investigated as hTRPV1 antagonists. Among them, compound 15 showed highly potent TRPV1 antagonism to capsaicin, with Ki(ant)=0.2nM, as well as antagonism to other activators, and it was efficacious in a pain model. A docking study of 15 with our hTRPV1 homology model indicates that there is crucial hydrogen bonding between the ring nitrogen and the receptor, contributing to its potency.