Fukushi H, Mabuchi H, Terashita Z, Nishikawa K, Sugihara H
Pharmaceutical Research Laboratories I, Takeda Chemical Industries, Ltd., Osaka, Japan.
Chem Pharm Bull (Tokyo). 1994 Mar;42(3):551-9. doi: 10.1248/cpb.42.551.
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.
制备了2-或3-取代的1-(2,3-二甲氧基-6,7-二氢-5H-苯并环庚烯-8-羰基)-4-(3,4,5-三甲氧基苯甲酰基)-和4-(3,4,5-三甲氧基苄基)哌嗪(2a-s, 3a, b)，并评估了它们对血小板活化因子(PAF)诱导的血小板聚集和血压降低的拮抗活性。2-甲氧基甲基衍生物(2f)在该系列中表现出最强的活性。对映体(R)-(+)-2f和(S)-(-)-2f通过几步反应由苄氧羰基-O-苄基-L-丝氨酸和D-丝氨酸合成。在结合实验中，(S)-(-)-2f对PAF受体的亲和力比R异构体高30倍。
