AGENTS FOR THE TREATMENT OF OVERACTIVE DETRUSOR .8. SYNTHESIS AND PHARMACOLOGICAL PROPERTIES OF 4,4-DIPHENYL-2-CYCLOALKENYLAMINES INCLUDINGFK584 AND 3,3-DIPHENYLCYCLOALKYLAMINES OR 4,4-DIPHENYLCYCLOALKYLAMINES

This article describes the synthesis of 4,4-diphenyl-2-cycloalkenylami nes (3, 5a) including FK584 (S(-)-3a) and 3,3- or 4,4-diphenylcycloalk ylamines (2, 4, 5b), and their inhibitory activities against detrusor contraction. The order of inhibitory activity (i.v.) of the N-tert-but ylamine derivatives against urinary bladder rhythmic contraction in ra ts was as follows: S(-)-4,4-diphenyl-2-cyclopentenylamine (FK584, S(-) -3a)>4,4-diphenylcyclohexylamine (5b)=R(-)-3,3-diphenylcyclopentylamin e (R(-)-4)greater than or equal to 3,3-diphenylcyclobutylamine (2)grea ter than or equal to terodiline hydrochloride (HCl) (1)=RS(+/-)-4,4-di phenyl-2-cyclohexenylamine (5a)>R(+)-4,4-diphenyl-2-cyclopentenylamine (R(+)-3a)greater than or equal to S(+)-3,3-diphenylcyclopentylamine ( S(+)-4). Although the inhibitory activity of FK584 and compounds R(-)- 4 and 5b against detrusor contraction in vitro induced with KCl in gui nea-pigs was less potent than that of terodiline HCl, their inhibitory activities against detrusor contractions in vitro induced by electric al field stimulation and carbachol were more potent than those of tero diline HCl.