Discovery of (S,E)-3-(2-fluorophenyl)-N-(1-(3-(pyridin-3-yloxy)phenyl)ethyl)-acrylamide as a potent and efficacious KCNQ2 (Kv7.2) opener for the treatment of neuropathic pain

Bioorg Med Chem Lett. 2013 Nov 15;23(22):6188-91. doi: 10.1016/j.bmcl.2013.08.092. Epub 2013 Sep 8.

Abstract

Acrylamide (S)-6, a potent and efficacious KCNQ2 (Kv7.2) opener, demonstrated significant activity in two models of neuropathic pain and in the formalin test, suggesting that KCNQ2 openers may be useful in the treatment of neuropathic pain including diabetic neuropathy.

Keywords: Acrylamide; Diabetic neuropathy; KCNQ2; Kv7.2; Neuropathic pain.

MeSH terms

  • Acrylamides / chemical synthesis
  • Acrylamides / chemistry*
  • Acrylamides / pharmacology*
  • Animals
  • KCNQ2 Potassium Channel / chemistry
  • KCNQ2 Potassium Channel / metabolism*
  • Male
  • Neuralgia / drug therapy*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Acrylamides
  • KCNQ2 Potassium Channel