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.
Original language | English |
---|---|
Pages (from-to) | 803-806 |
Number of pages | 4 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 25 |
Issue number | 4 |
DOIs | |
State | Published - 15 Feb 2015 |
Bibliographical note
Funding Information:This research was supported by Grants from Grunenthal , the Korea Health Technology R&D Project (HI13D2358), National Research Foundation of Korea ( R11-2007-107-02001-0 ), the National Leading Research Lab Program (2011-0028885), and in part by the Intramural Research Program of NIH, Center for Cancer Research, NCI (Project Z1A BC 005270).
Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.
Keywords
- Analgesic
- Molecular modeling
- TRPV1 antagonist
- Vanilloid receptor 1