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Published on: December 31, 2013
6,6-Fused heterocyclic ureas as highly potent TRPV1 antagonists
Wei Sun1, Hyo-Shin Kim2, Sunho Lee2
1Shenyang Pharmaceutical University, Shenyang 110016, China; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
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.
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