Discovery of piperidine carboxamide TRPV1 antagonists

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4569-72. doi: 10.1016/j.bmcl.2008.07.035. Epub 2008 Jul 15.

Abstract

A series of piperidine carboxamides were developed as potent antagonists of the transient receptor potential vanilloid-1 (TRPV1), an emerging target for the treatment of pain. A focused library of polar head groups led to the identification of a benzoxazinone amide that afforded good potency in cell-based assays. Synthesis and a QSAR model will be presented.

MeSH terms

  • Amides / chemistry*
  • Benzoxazines / chemistry
  • Benzoxazines / pharmacology*
  • Capsaicin / chemistry
  • Carrier Proteins / antagonists & inhibitors
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Molecular Conformation
  • Piperidines / chemistry*
  • Protein Binding
  • Quantitative Structure-Activity Relationship
  • Structure-Activity Relationship
  • TRPV Cation Channels / antagonists & inhibitors*

Substances

  • Amides
  • Benzoxazines
  • Carrier Proteins
  • Piperidines
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Capsaicin