Substituted biaryl oxazoles, imidazoles, and thiazoles as sodium channel blockers

Bioorg Med Chem Lett. 2010 Sep 15;20(18):5536-40. doi: 10.1016/j.bmcl.2010.07.064. Epub 2010 Jul 21.

Abstract

Voltage-gated sodium channels have been shown to play a critical role in neuropathic pain. With a goal to develop potent peripherally active sodium channel blockers, a series of low molecular weight biaryl substituted imidazoles, oxazoles, and thiazole carboxamides were identified with good in vitro and in vivo potency.

MeSH terms

  • Animals
  • Dogs
  • Humans
  • Imidazoles / chemistry
  • Imidazoles / metabolism
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use
  • Microsomes, Liver / metabolism
  • NAV1.7 Voltage-Gated Sodium Channel
  • Neuralgia / drug therapy*
  • Oxazoles / chemistry
  • Oxazoles / metabolism
  • Oxazoles / pharmacology
  • Oxazoles / therapeutic use*
  • Rats
  • Sodium Channel Blockers / chemistry
  • Sodium Channel Blockers / metabolism
  • Sodium Channel Blockers / pharmacology
  • Sodium Channel Blockers / therapeutic use*
  • Sodium Channels / metabolism*
  • Thiazoles / chemistry
  • Thiazoles / metabolism
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use*

Substances

  • Imidazoles
  • NAV1.7 Voltage-Gated Sodium Channel
  • Oxazoles
  • SCN9A protein, human
  • Sodium Channel Blockers
  • Sodium Channels
  • Thiazoles