Novel Thioxothiazolo[3,4-]quinazolin-5(4)-one Derivatives as BK Channel Activators for Urinary Incontinence.

Overactive bladder (OAB) is a syndrome causing a sudden and unstoppable need to urinate with significant global prevalence. Several drugs are used to treat OAB; however, they have various side effects. Therefore, new treatment options for OAB are required. A series of novel 5-oxo--phenyl-1-thioxo-4,5-dihydro-1-thiazolo[3,4-]quinazoline-3-carboxamide derivatives were synthesized and evaluated for their large-conductance voltage- and Ca-activated K channel activation through a cell-based fluorescence assay and electrophysiological recordings. Several compounds, including a 7-bromo substituent on the heterocyclic system, showed increased channel currents. Among the derivatives, compound exhibited potent activity with a half-maximal effective concentration (EC) of 2.89 μM, good oral pharmacokinetic properties (area under the curve and half-life), and efficacy in a spontaneously hypertensive rat model.