DSpace at EWHA: 6,6-Fused heterocyclic ureas as highly potent TRPV1 antagonists

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6,6-Fused heterocyclic ureas as highly potent TRPV1 antagonists

Authors: Sun W.; Kim H.-S.; Lee S.; Jung A.; Kim S.-E.; Ann J.; Yoon S.; Choi S.; Lee J.H.; Blumberg P.M.; Frank-Foltyn R.; Bahrenberg G.; Schiene K.; Stockhausen H.; Christoph T.; Frormann S.; Lee J.

Citation: Bioorganic and Medicinal Chemistry Letters vol. 25, no. 4, pp. 803 - 806

Keywords: Analgesic; Molecular modeling; TRPV1 antagonist; Vanilloid receptor 1

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) = 0.2 nM, 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. © 2015 Elsevier Ltd. All rights reserved.