(S)-N-[1-(4-cyclopropylmethyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-ethyl]-3-(2-fluoro-phenyl)-acrylamide is a potent and efficacious KCNQ2 opener which inhibits induced hyperexcitability of rat hippocampal neurons

Bioorg Med Chem Lett. 2004 Apr 19;14(8):1991-5. doi: 10.1016/j.bmcl.2004.01.069.

Abstract

(S)-N-[1-(4-Cyclopropylmethyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-ethyl]-3-(2-fluoro-phenyl)-acrylamide ((S)-2) was identified as a potent and efficacious KCNQ2 opener. This compound demonstrated significant activity in reducing neuronal hyperexcitability in rat hippocampal slices, and the inhibition mediated by (S)-2 was reversed by the KCNQ blocker linopirdine.

MeSH terms

  • Acrylamides / chemical synthesis
  • Acrylamides / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • KCNQ2 Potassium Channel
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / metabolism
  • Mice
  • Molecular Structure
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Oxazines / chemical synthesis
  • Oxazines / pharmacology*
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects*
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Potassium Channels, Voltage-Gated
  • Rats
  • Structure-Activity Relationship

Substances

  • Acrylamides
  • KCNQ2 Potassium Channel
  • KCNQ2 protein, human
  • Kcnq2 protein, rat
  • N-(1-(4-cyclopropylmethyl-3,4-dihydro-2H-benzo(1,4)oxazin-6-yl)ethyl)-3-(2-fluorophenyl)acrylamide
  • Oxazines
  • Potassium Channels
  • Potassium Channels, Voltage-Gated