Novel diphenylalkyl piperazine derivatives with dual calcium antagonistic and antioxidative activities.
Two types of novel diphenylalkyl piperazine derivatives containing the thio or aminopropanol moiety substituted by phenyl or benzyl group were synthesized, and evaluated for their calcium antagonistic and antioxidative activities. These compounds showed apparent inhibitions against KCl-induced contractions in isolated rat aorta. Among them, phenylamino compound 9 and benzylamino compound 13 also possessed potent inhibitory activities against auto-oxidative lipid peroxidations in canine brain homogenates. Two representative compounds 3a and 9 were evaluated for their inhibitory activities against KCl-induced contractions in isolated canine arteries (basilar, coronary, mesenteric, and renal). Both compounds showed the most potent inhibitions to basilar artery.
Pharmaceutical R & D Laboratories, POLA Chemical Industries Inc., 560, Kashio-cho, Totsuka-ku, Yokohama, Kanagawa 244-0812, Japan. m-kimura@pola.co.jp
Makoto
M
Kimura
Tomoko
T
Masuda
Koji
K
Yamada
Nobuo
N
Kubota
Nobuyuki
N
Kawakatsu
Masaki
M
Mitani
Kenichi
K
Kishii
Masato
M
Inazu
Takayuki
T
Namiki
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000037:antagonists & inhibitors*; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D004285:Dogs; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000975:Antioxidants; D002121:Calcium Channel Blockers; D010879:Piperazines; D002118:Calcium