Agents for the treatment of overactive detrusor. VII. Synthesis and pharmacological properties of 2,3- 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 detrusor, 2,3- and 3,4-diphenylcyclopentylamines (3), 2,3-diphenyl-2-cyclopentenylamines (4), and related compounds (5 and 18) were synthesized and evaluated for inhibitory activity (i.v.) against urinary bladder rhythmic contraction in rats. Among them, some compounds involving N-tert-butyl-2,3-diphenyl-2-cyclopentenylamine (4b) exhibited inhibitory activity against bladder contraction superior to that of terodiline (2). Mydriatic activity (i.v.) of compound 4b in rats, an index of its side effects due to antimuscarinic activity, was found to be relatively weak in comparison with its inhibitory activity against bladder contraction. The pharmacological profile of 4b was examined in comparison with that of terodiline. Most of the objective amines (3, 4, 5) were synthesized by preparation of Schiff bases from the corresponding cyclic ketones (6, 7, 8) and amines in the presence of TiCl4 in CH2Cl2 and subsequent reduction with NaBH4 in the presence of MeOH in one pot (method A).