Agents for the treatment of overactive detrusor. IV. Synthesis and structure-activity relationships of cyclic analogues of terodiline.

A series of pyrrolidine derivatives were synthesized and examined for inhibitory activity on detrusor contraction in vivo. Among those compounds, 5,5-dimethyl-2-(2,2-diphenylethyl)-3-isopropylidenepyrrolidine+ ++ hydrochloride (41.HCl), 2-(2,2-di(4-fluorophenyl)ethylene)-5,5-dimethyl-3-isopropylidenepyrro lidine hydrochloride (42.HCl), (+)-5,5-dimethyl-2-(N,N-diphenylaminomethyl)-3-isopropylidenepy rrolidine hydrochloride (+)-(43a.HCl), (-)-5,5-dimethyl-2-(N,N-diphenylaminomethyl)-3-isopropylidenepy rrolidine hydrochloride (-)-(43a.HCl), and 2-(N,N-di(4-fluorophenyl)aminomethyl)-5,5-dimethyl-3-isopropylidenepy rrolidine methanesulfonate (43b.MsOH) showed stronger inhibitory activity on detrusor contraction than terodiline.