Design, synthesis, and biological evaluation of novel diarylalkyl amides as TRPV1 antagonists

Bioorg Med Chem. 2009 May 15;17(10):3557-67. doi: 10.1016/j.bmc.2009.04.010. Epub 2009 Apr 11.

Abstract

We have developed a new class of diarylalkyl amides as novel TRPV1 antagonists. They exhibited potent (45)Ca(2+) uptake inhibitions in rat DRG neuron. In particular, the amide 59 was identified as a potent antagonist with IC(50) of 57 nM. The synthesis and structure-activity relationship of the diarylalkyl amides are also described.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology
  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Drug Design
  • Inhibitory Concentration 50
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology
  • TRPV Cation Channels / antagonists & inhibitors*
  • TRPV Cation Channels / metabolism
  • Tetrahydronaphthalenes / chemical synthesis*
  • Tetrahydronaphthalenes / chemistry
  • Tetrahydronaphthalenes / pharmacology

Substances

  • Amides
  • N-(3-cyano-5-fluoro-4-(methylsulfonamido)benzyl)-3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)propanamide
  • Sulfonamides
  • TRPV Cation Channels
  • Tetrahydronaphthalenes
  • Trpv1 protein, rat
  • Calcium