Synthesis and Platelet-Activating Factor (PAF)-Antagonistic Activities of Trisubstituted Piperazine Derivatives

2- or 3-Substituted 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclobepten-8- ylcarbonyl)-4-(3,4,5-trimethoxybenzoyl)- and 4-(3,4,5- trimethoxybenzyl)piperazines (2a - s, 3a, b) were prepared and evaluated for antagonistic activities against platelet-activating factor (PAF)-induced platelet aggregation and blood pressure reduction. The 2-methoxymethyl derivative (2f) showed the most potent activities in this series. The enantiomers (R)-(+)-2f and (S)-(-)-2f were synthesized from carbobenzoxy-O- benzyl-L- and D-serine in several steps. In the binding experiment. (S)-(-)- 2f showed thirty times greater affinity than the R isomer for the PAF receptor