川芎嗪衍生物的设计、合成及抗血小板凝集活性研究

Syntheses and Anti-Platelet Aggregation Activities Evaluation of Ligustrazine Derivatives

分别以川芎嗪(TMP)和邻苯二胺为起始原料,经KMn O4氧化、酯缩合、环化、还原等步骤合成了7个新型的川芎嗪衍生物,其结构经1H NMR、13C NMR及HRMS确证。并采用Born比浊法初步测试了化合物的体外抗血小板凝集活性。结果表明,化合物3和7对二磷酸腺苷(ADP)诱导的血小板凝集抑制率IC50分别为0.23mmol/L和0.27mmol/L,优于母体化合物川芎嗪(0.42mmol/L)。

Using ligustrazine（ TMP） and o-phenylenediamine as raw materials, seven derivatives were synthesized via KMn O4 oxidation,esterification,cyclization and reduction. The structures were confirmed by1 H NMR,13 C NMR and HRMS. The in vitro anti-platelet aggregation activities of the target compounds have been preliminarily tested by the Born turbidimetric method,and the experimental results showed that compounds 3（ IC50=0. 23 mmol/L） and 7（ IC50= 0. 27 mmol/L） have significant inhibitory activity for adenosine diphosphate（ ADP）induced platelet aggregation,higher than that of ligustrazine（ IC50= 0. 42 mmol/L）.