Agents for the Treatment of Overactive Detrusor. IV. Synthesis and Structure-Activity Relationships of Cyclic Analogues of Terodiline

Abstract

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-isopropylidenepyrrolidine hydrochloride (42·HCl), (+)-5, 5-dimethyl-2-(N, N-diphenylaminomethyl)-3-isopropylidenepyrrolidine hydrochloride (+)-(43a·HCl), (-)-5, 5-di-methyl-2-(N, N-diphenylaminomethyl)-3-isopropylidenepyrrolidine hydrochloride (-)-(43a·HCl), and 2-(N, N-di(4-fluorophenyl)aminomethyl)-5, 5-dimethyl-3-isopropylidenepyrrolidine methanesulfonate (43b·MsOH) showed stronger inhibitory activity on detrusor contraction than terodiline.