Discovery of N-(3-fluoro-4-methylsulfonamidomethylphenyl)urea as a potent TRPV1 antagonistic template

Bioorg Med Chem Lett. 2016 Aug 1;26(15):3603-7. doi: 10.1016/j.bmcl.2016.06.010. Epub 2016 Jun 7.

Abstract

A series of homologous analogues of prototype antagonist 1 and its urea surrogate were investigated as hTRPV1 ligands. Through one-carbon elongation in the respective pharmacophoric regions, N-(3-fluoro-4-methylsulfonamidomethylphenyl)urea was identified as a novel and potent TRPV1 antagonistic template. Its representative compound 27 showed a potency comparable to that of lead compound 1. Docking analysis of compound 27 in our hTRPV1 homology model indicated that its binding mode was similar with that of 1S.

Keywords: Analgesic; TRPV1 antagonists; Vanilloid receptor 1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Molecular Structure
  • Phenylurea Compounds / chemical synthesis
  • Phenylurea Compounds / chemistry
  • Phenylurea Compounds / pharmacology*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • TRPV Cation Channels / antagonists & inhibitors*

Substances

  • Phenylurea Compounds
  • Sulfonamides
  • TRPV Cation Channels
  • TRPV1 protein, human