Synthesis and evaluation of thiazole carboxamides as vanilloid receptor 1 (TRPV1) antagonists

Bioorg Med Chem Lett. 2005 Dec 1;15(23):5211-7. doi: 10.1016/j.bmcl.2005.08.100. Epub 2005 Oct 3.

Abstract

A thiazole derivative, 2-(2,6-dichlorobenzyl)-N-(4-isopropylphenyl) thiazole-4-carboxamide (1), was identified as a TRPV1 antagonist. We synthesized various thiazole analogs and evaluated them for their ability to block capsaicin- or acid-induced calcium influx in TRPV1-expressing CHO cells. The IC(50) values of the most potent antagonists were ca. 0.050microM in these assays.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacology*
  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Humans
  • Molecular Structure
  • Oxamic Acid / chemical synthesis
  • Oxamic Acid / chemistry
  • Oxamic Acid / pharmacology
  • Structure-Activity Relationship
  • TRPV Cation Channels / antagonists & inhibitors*
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry*
  • Thiazoles / pharmacology*

Substances

  • Amides
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Thiazoles
  • Oxamic Acid