2-Aryl substituted pyridine C-region analogues of 2-(3-fluoro-4- methylsulfonylaminophenyl)propanamides as highly potent TRPV1 antagonists

Hyungchul Ryu, Sejin Seo, Myeong Seop Kim, Mi Yeon Kim, Ho Shin Kim, Jihyae Ann, Phuong Thao Tran, Van Hai Hoang, Jieun Byun, Minghua Cui, Karam Son, Pankaz Kumar Sharma, Sun Choi, Peter M. Blumberg, Robert Frank-Foltyn, Gregor Bahrenberg, Babette Yvonne Koegel, Thomas Christoph, Sven Frormann, Jeewoo Lee

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

A series of 2-aryl pyridine C-region derivatives of 2-(3-fluoro-4- methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Multiple compounds showed highly potent TRPV1 antagonism toward capsaicin comparable to previous lead 7. Among them, compound 9 demonstrated anti-allodynia in a mouse neuropathic pain model and blocked capsaicin-induced hypothermia in a dose-dependent manner. Docking analysis of 9 with our hTRPV1 homology model provided insight into its specific binding mode.

Original languageEnglish
Pages (from-to)4044-4047
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number16
DOIs
StatePublished - 15 Aug 2014

Keywords

  • Capsaicin
  • Molecular modeling
  • Resiniferatoxin
  • TRPV1 antagonist
  • Vanilloid receptor 1

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