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

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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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 languageEnglish
Pages (from-to)803-806
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number4
StatePublished - 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.


  • Analgesic
  • Molecular modeling
  • TRPV1 antagonist
  • Vanilloid receptor 1


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