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目的寻找新的抗血小板聚集药物并研究4-甲氧基-N,N’-二(2-取代苯基)-1,3-苯二磺酰胺类化合物的不同2-位取代苯基对抗血小板聚集活性的影响。方法以吡考他胺为先导化合物,用取代苯磺酰氨基代替3-吡啶甲氨基对先导化合物进行结构改造:以苯甲醚为原料,采用文献方法与氯磺酸反应直接制得重要中间体4-甲氧基-1,3-苯二磺酰氯;该中间体与2-取代苯胺类化合物经胺解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。结果与结论共制得12个化合物(4a～4l),其化学结构由IR、1H-NMR和MS谱确证,其中9个化合物(4a～4c、4e～4i和4l)未见文献报道。药理试验结果表明,5个化合物表现出较好的体外抗血小板聚集活性:化合物4g、4f和4b的活性优于吡考他胺和阿司匹林;化合物4i的活性略低于阿司匹林;化合物4h的活性与吡考他胺相当。
Objective To find new anti-platelet aggregation drugs and to study the different 2-substituted phenyl-anti-platelets of 4-methoxy-N, N’-bis The effect of aggregation activity. Methods Pilotamine was used as the lead compound, and the substituted phenylsulfonamido was used to replace the 3-pyridylmethylamino group to modify the lead compound. The main intermediate was prepared by the literature method using chlorosulfonic acid as the starting material 4-methoxy-1,3-benzene disulfonyl chloride; the intermediate and 2-substituted aniline compounds obtained by aminolysis reaction of the target compound. Pirratamine and aspirin as positive control drugs, the Born turbidimetric method for the target compound in vitro anti-platelet aggregation activity of screening. RESULTS AND CONCLUSION Twelve compounds (4a ~ 4l) were prepared and their chemical structures were confirmed by IR, 1H-NMR and MS spectra. Nine compounds (4a ~ 4c, 4e ~ 4i and 4l) were not reported in the literature. Pharmacological test results showed that the five compounds showed good anti-platelet aggregation activity in vitro: the activity of compounds 4g, 4f and 4b was superior to that of picotamide and aspirin; the activity of compound 4i was slightly lower than that of aspirin; the activity of compound 4h and Piktamine quite.