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

• Published in: Chemical & pharmaceutical bulletin Vol. 44; no. 6; pp. 1188 - 1195
• Main Authors: TANIGUCHI, Kiyoshi, MIYAO, Yasuhiro, YAMANO, Katsuhiro, YAMAMOTO, Takao, TERAI, Takao, KUSUNOKI, Takahiro, TSUBAKI, Kazunori, SHIOKAWA, Youichi
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1996; Maruzen; Japan Science and Technology Agency
• Subjects: (±)-N-(2-hydroxy-1, 1-dimethylethyl)-4, 4-diphenyl-2-cyclopetenylamine; (±)-N-tert-butyl-4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-cyclopentenylamine; (±)-N-tert-butyl-4-(4-hydroxyphenyl)4-phenyl-2-cyclopenetenylamine; Amines - chemical synthesis; Amines - pharmacology; Amines - urine; Animals; Benzhydryl Compounds - chemical synthesis; Benzhydryl Compounds - pharmacology; Benzhydryl Compounds - urine; Biological and medical sciences; Biotransformation; detrusor contraction inhibition; Electric Stimulation; FK584; Gas Chromatography-Mass Spectrometry; Guinea Pigs; Humans; In Vitro Techniques; Medical sciences; metabolite; Muscarinic Agonists - chemical synthesis; Muscarinic Agonists - pharmacology; Muscarinic Agonists - urine; Muscle Relaxants, Central - chemical synthesis; Muscle Relaxants, Central - pharmacology; Pharmacology. Drug treatments; Stereoisomerism; Urinary Bladder - drug effects; Urinary Bladder - physiology; Urinary system; Human; Aminoalcohol; Vasodilator agent; Rodentia; Metabolism; Muscle contraction; Biological activity; Aminophenols; Urinary incontinence; Voiding dysfunction; Vertebrata; Mammalia; Guinea pig; Urinary system; Detrusor sphincter dyssynergia; Urinary bladder; Phenols; Racemate; Benzenic compound; Chemical synthesis; Monocyclic compound
• ISSN: 0009-2363; 1347-5223
• 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 thier inhibitory activity against detrusor contraction. (±)-N-tert-Butyl-4-(4-hydroxyphenyl)- and 4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-cyclopenetenyl-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 specrometry 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.