血小板激活因子拮抗剂的研究Ⅰ.2,5-二取代四氢呋喃衍生物的合成

Studies on Platelet-activating Factor Antagonists Ⅰ. Synthesis of 2,5-Disubstituted Tetrahydrofuran Derivatives

根据血小板激活因子(PAF)拮抗剂的结构特点和受体的模拟构象,设计并合成了8个以四氢呋喃为母核,在2、5位有不同取代基的化合物。初步药理实验显示,这些化合物对PAF诱导的兔血小板聚集(体外)均有不同程度的拮抗作用。其中化合物V_3、V_7在浓度为3×10^(-5)mol/L的抗擬作用(PAF:10^(-8)mol/L)分别为100.0%和90.9%。

Platelet-activating factor (PAF) has been established as an important mediator of pathophysiological reactions in human disease. On the basis of the structural features of known PAF antagonists and the putative conformation of PAF receptor, a series of 2, 5-disubstituted tetrahydrofuran derivatives were synthesized from aryl oxides and aryl aldehydes by acetylation, Mannich reaction. Michael-stetter reaction, reduction and cyclization. In vitro, rabbit platelet aggregation induced by PAF was antagonized by the compounds at different degree, and two of them, V_3, V_7 were the most active (100%. 90.9% inhibition respectively) at 3×10^(-5) mol/L concentration (PAF: 10^(-9) mol/L). Thus. we summarized the initial structure-activity relationship in this series.