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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、1 H-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26,位和34,位进行二氯代时化合物表现出很高的抗血小板聚集活性。
Objective To find a more active anti-platelet aggregation drug. Methods Anisole, 4-methoxy-1,3-benzenedicarboxylic acid, an important intermediate, was prepared by the reaction of Blanc, oxidation and chlorination using anisole as starting material. This intermediate was reacted with various haloanilines 4-methoxy-N, N’-bis (halophenyl) -1,3-benzenedicarboxamide was obtained as the target compound. Pyrimetamide and aspirin were used as positive control drugs, and Born turbidimetry The target compounds in vitro anti-platelet aggregation activity of screening. RESULTS AND CONCLUSION Totally 20 target compounds were prepared and the chemical structures were confirmed by IR, 1 H-NMR and MS spectra. Among them, 10 compounds were not reported in the literature. Pharmacological test results showed that the anti-platelet aggregation activity of seven compounds was superior to the positive control drugs picotamide and aspirin, of which compounds 5l and 5q had the highest activity. The effects of different halogen atoms on the platelet aggregation activity in the same position and at the same halogen atoms in different positions were investigated. The preliminary structure-activity relationship study showed that when the side chain phenyl 2 or 4 fluorine or iodine The substitutions were beneficial to the anti-platelet aggregation activity enhancement. When dichloro-substituted at the 26th, 34th, and 34th phenyl positions of the side chain, the compounds exhibited high anti-platelet aggregation activity.