川芎嗪/查耳酮类杂合物的设计、合成及抗血小板聚集活性

Design, synthesis and antiplatelet evaluation of tetramethylpyrazine/chalcone hybrids

摘要: 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/查耳酮类杂合物( 2 ~ 26 )，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 8 活性最强，对ADP诱导的血小板聚集的抑制作用(IC₅₀=0.14 mmol/L)是川芎嗪的9.1倍，查耳酮的10.5倍；对AA诱导的血小板聚集的抑制作用(IC₅₀=0.09 mmol/L)是川芎嗪的8.8倍，查耳酮的10.0倍，且略优于阿司匹林(IC₅₀=0.15 mmol/L)。

Abstract: In order to search for new antiplatelet agents with higher potency, a series of tetramethylpyrazine(TMP)/chalcone hybrids( 2 - 26 )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 8 was the most potent with IC₅₀ of 0. 14 mmol/L on ADP-induced platelet aggregation(9. 1 folds of TMP and 10. 5 folds of chalcone)and 0. 09 mmol/L on AA-induced platelet aggregation(8. 8 folds of TMP and 10. 0 folds of chalcone), which was superior to clinically used anti-platelet drug aspirin(ASP, IC₅₀=0. 15 mmol/L).