Subtype-selective Na(v)1.8 sodium channel blockers: identification of potent, orally active nicotinamide derivatives

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6812-5. doi: 10.1016/j.bmcl.2010.08.121. Epub 2010 Sep 18.


A series of aryl-substituted nicotinamide derivatives with selective inhibitory activity against the Na(v)1.8 sodium channel is reported. Replacement of the furan nucleus and homologation of the anilide linker in subtype-selective blocker A-803467 (1) provided potent, selective derivatives with improved aqueous solubility and oral bioavailability. Representative compounds from this series displayed efficacy in rat models of inflammatory and neuropathic pain.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Niacinamide / chemistry
  • Niacinamide / pharmacokinetics
  • Niacinamide / pharmacology*
  • Rats
  • Sodium Channel Blockers / administration & dosage
  • Sodium Channel Blockers / chemistry
  • Sodium Channel Blockers / pharmacokinetics
  • Sodium Channel Blockers / pharmacology*
  • Structure-Activity Relationship


  • Sodium Channel Blockers
  • Niacinamide