Identification of novel 1,2,3,6-tetrahydropyridyl-substituted benzo[d]thiazoles: Lead generation and optimization toward potent and orally active EPreceptor antagonists.

Abstract

Herein we described the design, synthesis and evaluation of a novel series of benzo[d]thiazole derivatives toward an orally active EPantagonist. Lead generation studies provided benzo[d]thiazole core from the four designed scaffolds. Optimization of this scaffold in terms of EPantagonist potency and ligand-lipophilicity efficiency (LLE; pIC-clogP) led to a 1,2,3,6-tetrahydropyridyl-substituted benzo[d]thiazole derivative, 7r (IC1.1nM; LLE 4.7), which showed a good pharmacological effect when administered intraduodenally in a 17-phenyl trinor-PGE2 (17-PTP)-induced overactive bladder model in rats.