The antiplatelet aggregation drug is one of the hot research topics. The aim of this study is to search new antiplatelet aggregation drugs with high activity. 4-Methoxy-N,N'-bis (2,4,6-trichlorophenyl) -l,3-isophthalamide(P12) as the lead compound and 2,4,6-trichlorophenyl replaced with halogen-substituted phenyl,N,N'-bis-(halogenophenyl)-4-methoxybenzene-l ,3-isophthalarnide derivatives were designed. Starting from anisole via Blanc chloromethylation, oxidation and chlorination, the key intermediate 4-me-thoxy-1,3-phthaloyl chloride was obtained,and then it was reacted with halogenophenylamine. Twenty target compounds were synthesized and ten among them were not reported yet,and their structures were confirmed by IR,1H-NMR and MS. Their in vitro antiplatelet aggregation activity were carried out by Born turbidimet-ric method. The results showed that seven of them exhibit superior antiplatelet aggregation activity compared to the positive drug picotamide and asprin. The structure activity relationship showed that compounds with an ortho or para halogen-substitutent on the phenyl have good activity. So are the compounds with two chlorine substirutents on 3,4-position or 2,6-position.%目的 寻找活性更好的抗血小板聚集药物.方法 以苯甲醚为原料,经Blanc反应、氧化和氯代反应制得重要中间体4-甲氧基-1,3-苯二甲酰氯,该中间体与不同的卤代苯胺类化合物反应制得目标化合物4-甲氧基-N,N'-二(卤代苯基)-1,3-苯二甲酰胺类化合物；以吡考他胺和阿司匹林为阳性对照药,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 共制得20个目标化合物,其化学结构经IR、1H-NMR和MS谱确证,其中10个化合物未见文献报道.药理试验初筛结果表明,7个化合物抗血小板聚集活性优于阳性对照药吡考他胺和阿司匹林,其中化合物5l和5q的活性最高.考察了不同卤原子在相同位置和相同卤原子在不同位置上的取代化合物对抗血小板聚集活性的影响规律,初步构效关系研究表明,当侧链苯基的2位或4位进行氟或碘一取代时有利于抗血小板聚集活性的增强；当侧链苯基的2,6位和3,4位进行二氯代时化合物表现出很高的抗血小板聚集活性.
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