川芎嗪衍生物合成及抗血小板聚集活性研究

Synthesis and Anti-Platelet Aggregation Activity Evaluation of Ligustrazine Derivatives

摘要: 本文基于药物设计的生物电子等排和拼合原理，设计、合成了一系列川芎嗪类衍生化合物A~H，以期得到活性较强的抗血小板聚集药物。结果表明，目标化合物对二磷酸腺苷(ADP)和花生四烯酸(AA)诱导的血小板聚集均显示不同程度的抑制；其中化合物H活性最强，对ADP诱导的血小板聚集的抑制作用(IC50 = 8.52 μmol/L)是川芎嗪的5.2倍，对AA诱导的血小板聚集的抑制作用(IC50 = 12.08 μmol/L)是川芎嗪的3.9倍，是具有良好开发前景的候选化合物。

Abstract: In order to search for new anti-platelet agents with higher potency, a series of Ligustrazine deriva-tives were synthesized and evaluated based on the principle of bioisostere and hybridization. They exerted inhibitory activity against adenosine diphosphate (ADP)-induced and arachidonic acid (AA)-induced platelet aggregation to varied extent. Among them, compound H was the most potent with IC50 of 8.52 μmol/L on ADP-induced platelet aggregation (5.2 folds of TMP) and 12.08 μmol/L on AA-induced platelet aggregation (3.9 folds of TMP), which may be utilized as lead compound for further investigation.