AGENTS FOR THE TREATMENT OF OVERACTIVE DETRUSOR .7. SYNTHESIS AND PHARMACOLOGICAL PROPERTIES OF 2,3-DIPHENYLCYCLOPENTYLAMINES AND 3,4-DIPHENYLCYCLOPENTYLAMINES, 2,3-DIPHENYL-2-CYCLOPENTENYLAMINES, AND RELATED-COMPOUNDS

As part of our search for new agents for the treatment of overactive d etrusor, 2,3- and 3,4-diphenyl-cyclopentylamines (3), 2,3-diphenyl-2-c yclopentenylamines (4), and related compounds (5 and 18) were synthesi zed and evaluated for inhibitory activity (i.v.) against urinary bladd er rhythmic contraction in rats. Among them, some compounds involving N-tert-butyl-2,3-diphenyl-2-cyclopentenylamine (4b) exhibited inhibito ry activity against bladder contraction superior to that of terodiline (2). Mydriatic activity (i.v.) of compound 4b in rats, an index of it s side effects due to antimuscarinic activity, was found to be relativ ely weak in comparison with its inhibitory activity against bladder co ntraction. The pharmacological profile of 4b was examined in compariso n with that of terodiline. Most of the objective amines (3, 4, 5) were synthesized by preparation of Schiff bases from the corresponding cyc lic ketones (6, 7, 8) and amines in the presence of TiCl4 in CH2Cl2 an d subsequent reduction with NaBH4 in the presence of MeOH in one pot ( method A).