Novel 5-cyclopropyl-1,4-benzodiazepin-2-ones as potent and selective I(Ks)-blocking class III antiarrhythmic agents

Bioorg Med Chem Lett. 2003 Mar 24;13(6):1165-8. doi: 10.1016/s0960-894x(03)00049-0.

Abstract

Novel 5-cyclopropyl-1,4-benzodiazepin-2-ones having various N-l substituents were identified as potent and selective blockers of the slowly activating cardiac delayed rectifier potassium current (I(Ks)). Compound 11 is the most potent I(Ks) channel blocker reported to date.

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / chemical synthesis*
  • Anti-Arrhythmia Agents / metabolism
  • Anti-Arrhythmia Agents / pharmacology*
  • Benzodiazepines / chemical synthesis*
  • Benzodiazepines / metabolism
  • Benzodiazepines / pharmacology*
  • Delayed Rectifier Potassium Channels
  • Dogs
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Heart Rate / drug effects
  • Hemodynamics / drug effects
  • Humans
  • In Vitro Techniques
  • Microsomes, Liver / metabolism
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / chemical synthesis*
  • Potassium Channel Blockers / metabolism
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels / drug effects*
  • Potassium Channels, Voltage-Gated*
  • Refractory Period, Electrophysiological / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Arrhythmia Agents
  • Delayed Rectifier Potassium Channels
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Benzodiazepines