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

Article abstract of DOI:10.1248/cpb.44.1188

We synthesized the racemates of five presumed metabolites (1b-f) of (s)- (-)-N-tert-butyl-4,4-diphenyl-2-cyclopentenylamine hydrochloride (FK584, S(- )-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-cyclopentenyl- amines (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.

Full text of DOI:10.1248/cpb.44.1188

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