The synthesis and structure-activity relationships of 1,3-diaryl 1,2,4-(4H)-triazol-5-ones: a new class of calcium-dependent, large conductance, potassium (maxi-K) channel opener targeted for urge urinary incontinence

Bioorg Med Chem Lett. 2002 Apr 8;12(7):1117-20. doi: 10.1016/s0960-894x(02)00099-9.

Abstract

A series of 1,3-diaryl 1,2,4-(4H)-triazol-5-ones was prepared and shown by electrophysiological analysis to activate a cloned maxi-K channel mSlo (or hSlo) expressed in Xenopus laevis oocytes. The effects of these structurally novel maxi-K channel openers on bladder contractile function were studied in vitro using isolated rat bladder strips pre-contracted with carbachol. Several 1,3-diaryl 1,2,4-(4H)-triazol-5-one derivatives were found to be potent smooth muscle relaxants but this activity did not completely correlate with maxi-K channel opening.

MeSH terms

  • Animals
  • Azo Compounds / chemical synthesis*
  • Azo Compounds / pharmacology*
  • Calcium / metabolism
  • Carbachol / pharmacology
  • Cells, Cultured / drug effects
  • Electrophysiology
  • Humans
  • Large-Conductance Calcium-Activated Potassium Channels
  • Male
  • Mice
  • Microinjections
  • Models, Molecular
  • Muscle Relaxation / drug effects
  • Muscle, Smooth / physiology
  • Oocytes / drug effects*
  • Oocytes / physiology*
  • Potassium Channels, Calcium-Activated / drug effects*
  • Potassium Channels, Calcium-Activated / genetics
  • Potassium Channels, Calcium-Activated / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Structure-Activity Relationship
  • Urinary Bladder / metabolism
  • Urinary Incontinence / drug therapy*
  • Xenopus laevis

Substances

  • Azo Compounds
  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels, Calcium-Activated
  • RNA, Messenger
  • Carbachol
  • Calcium