Novel Thioxothiazolo[3,4- a ]quinazolin-5(4 H )-one Derivatives as BK Ca 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- N -phenyl-1-thioxo-4,5-dihydro-1 H -thiazolo[3,4- a ]quinazoline-3-carboxamide derivatives were synthesized and evaluated for their large-conductance voltage- and Ca 2+ -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 12h exhibited potent in vitro activity with a half-maximal effective concentration (EC 50 ) of 2.89 μM, good oral pharmacokinetic properties (area under the curve and half-life), and in vivo efficacy in a spontaneously hypertensive rat model.