2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists

Jihyae Ann, Yooran Ki, Suyoung Yoon, Myeong Seop Kim, Jung Un Lee, Changhoon Kim, Sunho Lee, Aeran Jung, Jisoo Baek, Sunhye Hong, Sun Choi, Larry V. Pearce, Timothy E. Esch, Noe A. Turcios, Nancy E. Lewin, Adebowale E. Ogunjirin, Brienna K.A. Herold, Anna K. McCall, Peter M. Blumberg, Jeewoo Lee

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10 Scopus citations


A series of 2-sulfonamidopyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamide were investigated as hTRPV1 ligands. Systematic modification on the 2-sulfonamido group provided highly potent TRPV1 antagonists. The N-benzyl phenylsulfonamide derivatives 12 and 23 in particular showed higher affinities than that of lead compound 1. Compound 12 exhibited strong analgesic activity in the formalin pain model. Docking analysis of its chiral S-form 12S in our hTRPV1 homology model indicated that its high affinity might arise from additional hydrophobic interactions not present in lead compound 1S.

Original languageEnglish
Pages (from-to)1231-1240
Number of pages10
JournalBioorganic and Medicinal Chemistry
Issue number6
StatePublished - 15 Mar 2016

Bibliographical note

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© 2016 Elsevier Ltd. All rights reserved.


  • Analgesic
  • TRPV1 antagonists
  • Vanilloid receptor 1


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