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.
Take
K
K
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Okumura
K
K
Tsubaki
K
K
Terai
T
T
Shiokawa
Y
Y
D000818:Animals; D002082:Butylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010084:Oxidation-Reduction; D010276:Parasympatholytics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects*
D002082:Butylamines; D010276:Parasympatholytics; C010637:terodiline