3-Amino-1,5-benzodiazepinones: potent, state-dependent sodium channel blockers with anti-epileptic activity

Bioorg Med Chem Lett. 2008 Mar 15;18(6):1963-6. doi: 10.1016/j.bmcl.2008.01.123. Epub 2008 Feb 7.

Abstract

A series of 3-amino-1,5-benzodiazepinones were synthesized and evaluated as potential sodium channel blockers in a functional, membrane potential-based assay. One member of this series displayed subnanomolar, state-dependent sodium channel block, and was orally efficacious in a mouse model of epilepsy.

MeSH terms

  • Animals
  • Anticonvulsants / chemical synthesis
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / pharmacology*
  • Benzodiazepinones / chemical synthesis
  • Benzodiazepinones / pharmacokinetics
  • Benzodiazepinones / pharmacology*
  • Electrophysiology
  • Electroshock
  • Epilepsy / drug therapy*
  • Epilepsy / metabolism
  • Ether-A-Go-Go Potassium Channels / antagonists & inhibitors*
  • Ether-A-Go-Go Potassium Channels / metabolism
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Mice
  • Molecular Structure
  • Rats
  • Sodium Channel Blockers / chemical synthesis
  • Sodium Channel Blockers / pharmacokinetics
  • Sodium Channel Blockers / pharmacology*

Substances

  • Anticonvulsants
  • Benzodiazepinones
  • Ether-A-Go-Go Potassium Channels
  • Sodium Channel Blockers