Agents for the treatment of overactive detrusor. VIII. Synthesis and pharmacological properties of 4,4-diphenyl-2-cycloalkenylamines including FK584 and 3,3- or 4,4-diphenylcycloalkylamines.
This article describes the synthesis of 4,4-diphenyl-2-cycloalkenylamines (3, 5a) including FK584 (S(-)-3a) and 3,3- or 4,4-diphenylcycloalkylamines (2, 4, 5b) and their inhibitory activities against detrusor contraction. The order of inhibitory activity (i.v.) of the N-tert-butylamine derivatives against urinary bladder rhythmic contraction in rats was as follows: S(-)-4,4-diphenyl-2-cyclopentenylamine (FK584, S(-)-3a) > 4,4-diphenylcyclohexylamine (5b) = R(-)-3,3-diphenylcyclopentylamine (R(-)-4) > or = 3,3-diphenylcyclobutylamine (2) > or = terodiline hydrochloride (HCl) (1) = RS(+/-)-4,4-diphenyl-2-cyclohexenylamine (5a) > R(+)-4,4-diphenyl-2-cyclopentenylamine (R(+)-3a) > or = S(+)-3,3-diphenylcyclopentylamine (S(+)-4). Although the inhibitory activity of FK584 and compounds R(-)-4 and 5b against detrusor contraction in vitro induced with KCl in guinea-pigs was less potent than that of terodiline HCl, their inhibitory activities against detrusor contractions in vitro induced by electrical field stimulation and carbachol were more potent than those of terodiline HCl.
Taniguchi
K
K
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Okumura
K
K
Take
K
K
Tsubaki
K
K
Terai
T
T
Nakanishi
I
I
Shiokawa
Y
Y
D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001559:Benzhydryl Compounds / Q000737:chemistry / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology
D000588:Amines; D001559:Benzhydryl Compounds; C092685:4,4-diphenyl-2-cyclopentenylamine