Agents for the Treatment of Overactive Detrusor. IX. Synthesis and Pharmacological Properties of Metabolites of N-tert-Butyl-4,4-diphenyl-2-cyclopentenylamine(FK584) in Human Urine.

We synthesized the racemates of five presumed metabolites (1b-f) of (S)-(-)-N-tert-butyl-4,4-diphenyl-2-cyclopentenylamine hydrochloride (FK584, S(-1)-1a), a novel agent for the treatment of overactive detrusor syndrome, in order to confirm the structures of the metabolites and also to evaluate their inhibitory activity against detrusor contraction. (±)-N-tert-Butyl-4-(4-hydroxyphenyl)- and 4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-cyclopentenylamines (1b-e) were synthesized via 5-(4-methoxyphenyl)- and 5-(4-benzyloxy-3-methoxyphenyl)-5-phenyl-2-cyclopenten-1-one (9g, h), respectively. Compounds 1b-f prepared in this study were identical with the metabolites in human urine in gas chromatography-mass spectrometry and analytical HPLC. The inhibitory activity of compounds 1b-f against detrusor contraction in vitro induced by electrical field stimulation in guinea-pigs was less potent than that of FK584.