Substituted biaryl pyrazoles as sodium channel blockers

Bioorg Med Chem Lett. 2010 Sep 15;20(18):5480-3. doi: 10.1016/j.bmcl.2010.07.080. Epub 2010 Jul 24.

Abstract

Voltage-gated sodium channels have been shown to play a critical role in neuropathic pain. A series of low molecular weight biaryl substituted pyrazole carboxamides were identified with good in-vitro potency and in-vivo efficacy. Compound 26, a Nav1.7 blocker has excellent efficacy in the Chung model of neuropathic pain.

MeSH terms

  • Animals
  • Dogs
  • Haplorhini
  • Humans
  • Microsomes, Liver / metabolism
  • NAV1.7 Voltage-Gated Sodium Channel
  • Neuralgia / drug therapy*
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*
  • Rats
  • Sodium Channel Blockers / chemistry*
  • Sodium Channel Blockers / pharmacokinetics
  • Sodium Channel Blockers / pharmacology
  • Sodium Channel Blockers / therapeutic use*
  • Sodium Channels / metabolism*
  • Structure-Activity Relationship

Substances

  • NAV1.7 Voltage-Gated Sodium Channel
  • Pyrazoles
  • SCN9A protein, human
  • Sodium Channel Blockers
  • Sodium Channels