4-甲氧基-1,3-苯二甲酸-4′-取代苯酚二酯类化合物的合成及其抗血小板聚集活性研究

目的 寻找新的高效低毒的血小板聚集抑制剂。方法 以 4-甲氧基-N,N′-二苯基-1,3-苯二甲酰胺为先导化合物，用 4-取代苯氧基代替苯氨基对先导化合物进行结构改造：以苯甲醚为原料，采用文献方法经 3 步反应制得重要中间体4-甲氧基-1,3-苯二甲酰氯；该中间体与 4-取代苯酚类化合物进行取代反应制得目标化合物。以吡考他胺和阿司匹林为阳性对照药物，采用 Born 比浊法对目标化合物进行体外抗血小板聚集活性初筛。结果与结论 包括先导化合物在内共制得 9 个化合物，其中 8 个未见文献报道，目标化合物的结构均经 IR、¹H-NMR 和 MS 谱确证。药理试验结果表明，化合物 PO3 的抗血小板聚集活性最高，优于吡考他胺和阿司匹林，化合物 PO4、PO5 和 PO7 的活性超过吡考他胺。

Synthesis and anti-platelet aggregation activities of bis(4-substituted-phenyl)-4-methoxyisophthalates

To modify the structure of 4-methoxy-N,N′-diphenylisophthalamide and to obtain novel anti-platelet aggregating drugs,a series of bis（4-substituted-phenyl）-4-methoxyisophthalates were designed and synthesized from 4-methoxy-1,3-benzenedicarboxyl chloride and different 4-substituted-phenol.And their che-mical structures were assigned by IR,1H-NMR and MS spectroscopy.Among them,eight compounds were first reported in this paper.Their activities in vitro on anti-platelet aggregating were tested and assessed with picotamide and aspirin as reference drugs.The results showed that compound PO3（inhibitory rate：77.4%） has significant anti-platelet aggregation activity,superior to both reference drug picotamide（inhibitory rate：56.5%） and aspirin（inhibitory rate：69.6%）,while three compounds PO4,PO5 and PO7 superior to that of picotamide.