4-Aryl-3-(hydroxyalkyl)quinolin-2-ones: novel maxi-K channel opening relaxants of corporal smooth muscle targeted for erectile dysfunction

J Med Chem. 2003 Jul 3;46(14):2819-22. doi: 10.1021/jm030005h.

Abstract

Novel 4-aryl-3-(hydroxyalkyl)quinoline-2-one derivatives were prepared and evaluated as openers of the cloned maxi-K channel hSlo expressed in Xenopus laevis oocytes by utilizing electrophysiological methods. The effect of these maxi-K openers on corporal smooth muscle was studied in vitro using isolated rabbit corpus cavernosum. From this study, a potent maxi-K opener was identified as an effective relaxant of rabbit corporal smooth muscle and shown to be active in an in vivo animal model of male erectile function.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Electric Stimulation
  • Erectile Dysfunction / drug therapy
  • In Vitro Techniques
  • Large-Conductance Calcium-Activated Potassium Channels
  • Male
  • Muscle Relaxation / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology
  • Penile Erection / drug effects
  • Penis / drug effects*
  • Penis / innervation
  • Penis / physiology
  • Potassium Channels, Calcium-Activated / drug effects*
  • Pressure
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology
  • Rabbits
  • Rats
  • Rats, Inbred F344
  • Structure-Activity Relationship

Substances

  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Quinolones