Synthesis and Platelet-Activating Factor (PAF)-Antagonistic Activities of 1, 4-Disubstituted Piperazine Derivatives

Abstract

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.