Synthesis of the metabolites of 4-(2-methyl-1H-imidazol-1-yl)-2,2- diphenylbutanamide (KRP-197/ONO-8025)

Abstract

We synthesized the six presumed metabolites (2-7) of 4-(2-methyl-1H- imidazol-1-yl)-2,2-diphenylbutanamide [KRP-197/ONO-8025, 1], a urinary incontinence therapeutic agent, in order to confirm the structures of the metabolites. Metabolite (2) was synthesized via glucuronidaion of compound (1) and methyl 2,3,4-tri-Obenzoyl-1-methanesulfonyl-α-D-glucopyranuronate. Metabolite (3) was synthesized via 3-(tert-butoxycarbonyl)-2-methyl-1,3- imidazolidine-4,5-dione. Metabolites (4-7) were synthesized via 4-amino-2-diphenylbutanamide, respectively. The structures of the metabolites (2-7) in humans were identified by means of synthesis of the authentic compounds. © 2007 Pharmaceutical Society of Japan.