title: Synthesis and platelet-activating factor (PAF)-antagonistic activities of trisubstituted piperazine derivatives.
abstract: 2- or 3-Substituted 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-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.
authors.affiliation: Pharmaceutical Research Laboratories I, Takeda Chemical Industries, Ltd., Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fukushi
authors.forename: H
authors.initials: H
authors.lastname: Mabuchi
authors.forename: Z
authors.initials: Z
authors.lastname: Terashita
authors.forename: K
authors.initials: K
authors.lastname: Nishikawa
authors.forename: H
authors.initials: H
authors.lastname: Sugihara
mesh_terms: 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
chemical_list: D010879:Piperazines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors