(S,E)-N-[1-(3-heteroarylphenyl)ethyl]-3-(2-fluorophenyl)acrylamides: synthesis and KCNQ2 potassium channel opener activity

Bioorg Med Chem Lett. 2005 Jan 17;15(2):363-6. doi: 10.1016/j.bmcl.2004.10.065.

Abstract

Replacement of the morpholinyl moiety in (S,E)-N-[1-(3-morpholinophenyl)ethyl]-3-phenylacrylamide (1) with heteroaryl groups led to the identification of (S,E)-N-1-[3-(6-fluoropyridin-3-yl)phenyl]ethyl-3-(2-fluorophenyl)acrylamide (5) as a potent KCNQ2 potassium channel opener. Among this series of heteroaryl substituted acrylamides, (S,E)-N-1-[3-(1H-pyrazol-1-yl)phenyl]ethyl-3-(2-fluorophenyl)acrylamide (9) exhibits balanced potency and efficacy. The syntheses and the KCNQ2 opener activity of this series of acrylamides are described.

MeSH terms

  • Acrylamides / chemical synthesis
  • Acrylamides / pharmacology
  • Action Potentials / drug effects*
  • Animals
  • Cell Line
  • Dose-Response Relationship, Drug
  • Humans
  • KCNQ2 Potassium Channel
  • Molecular Structure
  • Potassium Channels, Voltage-Gated / metabolism*

Substances

  • Acrylamides
  • KCNQ2 Potassium Channel
  • KCNQ2 protein, human
  • Potassium Channels, Voltage-Gated