Synthesis and platelet-activating factor (PAF)-antagonistic activities of 1,4-disubstituted piperazine derivatives.
During the screening of novel platelet-activating factor (PAF) antagonists, we found that 1-(6-methoxy-3,4-dihydro-2-naphthoyl)-4- (3,4,5-trimethoxybenzyl)piperazine and its 4-(3,4,5- trimethoxybenzoyl)piperazine derivatives (1b, 2b) exerted in vitro and in vivo PAF-antagonistic activities. Modifications of the 1-acyl group, the substituent at the 4-position and the piperazine ring of 1a and 2b were examined and from this series 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl++ +)-4- (3,4,5-trimethoxybenzoyl)piperazine (2g) was found to be one of the most potent PAF antagonists.
Fukushi
H
H
Pharmaceutical Research Laboratories, I, Takeda Chemical Industries, Ltd., Osaka, Japan.
Mabuchi
H
H
Itoh
K
K
Terashita
Z
Z
Nishikawa
K
K
Sugihara
H
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D010879:Piperazines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors