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.

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.