(S)-N-[1-(3-morpholin-4-ylphenyl)ethyl]- 3-phenylacrylamide: an orally bioavailable KCNQ2 opener with significant activity in a cortical spreading depression model of migraine

J Med Chem. 2003 Jul 17;46(15):3197-200. doi: 10.1021/jm034073f.

Abstract

(S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenylacrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride.

MeSH terms

  • Acrylamides / chemical synthesis*
  • Acrylamides / chemistry
  • Acrylamides / pharmacology
  • Administration, Oral
  • Animals
  • Biological Availability
  • Cell Line
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / physiopathology
  • Disease Models, Animal
  • Dogs
  • Humans
  • Ion Channel Gating
  • KCNQ2 Potassium Channel
  • Migraine Disorders / metabolism
  • Migraine Disorders / physiopathology*
  • Morpholines / chemical synthesis*
  • Morpholines / chemistry
  • Morpholines / pharmacology
  • Oocytes / drug effects
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects*
  • Potassium Channels / physiology
  • Potassium Channels, Voltage-Gated
  • Rats
  • Rats, Sprague-Dawley
  • Stereoisomerism
  • Structure-Activity Relationship
  • Xenopus laevis

Substances

  • Acrylamides
  • KCNQ2 Potassium Channel
  • KCNQ2 protein, human
  • Kcnq2 protein, rat
  • Morpholines
  • N-(1-(3-morpholin-4-ylphenyl)ethyl)-3-phenylacrylamide
  • Potassium Channels
  • Potassium Channels, Voltage-Gated