title: 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.
abstract: We synthesized the racemates of the 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-hydroxyphenyl)- and 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.
authors.affiliation: New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Miyao
authors.forename: K
authors.initials: K
authors.lastname: Yamano
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Terai
authors.forename: T
authors.initials: T
authors.lastname: Kusunoki
authors.forename: K
authors.initials: K
authors.lastname: Tsubaki
authors.forename: Y
authors.initials: Y
authors.lastname: Shiokawa
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000652:urine; D000818:Animals; D001559:Benzhydryl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000652:urine; D001711:Biotransformation; D004558:Electric Stimulation; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D018721:Muscarinic Agonists / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000652:urine; D009125:Muscle Relaxants, Central / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology
chemical_list: D000588:Amines; D001559:Benzhydryl Compounds; D018721:Muscarinic Agonists; D009125:Muscle Relaxants, Central; C092685:4,4-diphenyl-2-cyclopentenylamine