Aminoquinazolines as TRPV1 antagonists: modulation of drug-like properties through the exploration of 2-position substitution

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4573-7. doi: 10.1016/j.bmcl.2008.07.036. Epub 2008 Jul 15.

Abstract

A focused SAR exploration of the lead 4-aminoquinazoline TRPV1 antagonist 2 led to the discovery of compound 18. In rats, compound 18 is readily absorbed following oral dosing and demonstrates excellent in vivo potency and efficacy in an acute inflammatory pain model.

MeSH terms

  • Aminoquinolines / chemistry
  • Aminoquinolines / pharmacology*
  • Animals
  • Chemistry, Pharmaceutical / methods*
  • Dogs
  • Drug Design
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels / chemistry
  • Inflammation / drug therapy
  • Kinetics
  • Models, Chemical
  • Molecular Conformation
  • Pain / drug therapy
  • Pharmaceutical Preparations / chemistry
  • Rats
  • TRPV Cation Channels / antagonists & inhibitors*
  • TRPV Cation Channels / chemistry

Substances

  • Aminoquinolines
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • Pharmaceutical Preparations
  • TRPV Cation Channels
  • TRPV1 protein, human
  • TRPV1 receptor