AGENTS FOR THE TREATMENT OF OVERACTIVE DETRUSOR .5. SYNTHESIS AND INHIBITORY ACTIVITY ON DETRUSOR CONTRACTION OF N-TERT-BUTYL-4,4-DIPHENYL-2-CYCLOPENTENYLAMINE

N-tert-Butyl-4,4-diphenyl-2-cyclopentenylamine ((+/-)-3) was designed to restrict the conformation of terodiline 1 and was synthesized in a 6-step approach starting with diphenylacetaldehyde (10) or in a 4-step approach starting with 2,2-diphenyl-4-pentenoic acid (17). Using di-p -toluoyltartaric acid as a resolving agent, the synthetic (+/-)-3 was resolved into its optically pure forms, (-)- and(+)-3. The(-)-enantiom er (-)-3 . HCl (FK584) showed about ten times more potent inhibitory a ctivity on urinary bladder rhythmic contraction in rats (ED(30) = 0.18 mg/kg, i.v.) than terodiline (ED(30) = 1.9 mg/kg, i.v.), while the ()-enantiomer (+)-3 . HCl showed no inhibitory activity at 1.0 mg/kg i. v.Compound (-)-3 . HCl (FK584) has pharmacological properties similar to those of terodiline, as evaluated by in vitro assay and is currentl y in clinical development for the treatment of overactive detrusor.