川芎嗪衍生物。第 5 部分：新型川芎嗪氧基肉桂酸衍生物作为有效心血管药物的设计、合成与生物评价。

Ligustrazine derivatives. Part 5: design, synthesis and biological evaluation of novel ligustrazinyloxy-cinnamic acid derivatives as potent cardiovascular agents.

机构信息

Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No 44, Wenhuaxi Road, Jinan 250012, PR China.

出版信息

Eur J Med Chem. 2011 Nov;46(11):5609-15. doi: 10.1016/j.ejmech.2011.09.030. Epub 2011 Sep 29.

DOI:10.1016/j.ejmech.2011.09.030

PMID:21993151

Abstract

A series of novel ligustrazinyloxy-cinnamic acid derivatives were designed, synthesized and evaluated for their inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation in vitro, and also assayed for their protective effect against hydrogen peroxide (H(2)O(2))-induced oxidative damage on ECV-304 cells. Some compounds exhibited high activity in one or both of the assays, of which, compound 2e displayed the highest protective effect on the proliferation of the damaged ECV-304 cells (EC(50) = 0.020 mM), and compound 2f was the most active anti-platelet aggregation agent (EC(50) = 0.054 mM). Structure-activity relationships were briefly discussed.

摘要

设计、合成了一系列新型的川芎嗪氧基肉桂酸衍生物，并评价了它们对体外二磷酸腺苷（ADP）诱导的血小板聚集的抑制作用，还检测了它们对过氧化氢（H₂O₂）诱导的ECV-304 细胞氧化损伤的保护作用。一些化合物在一种或两种测定中表现出高活性，其中，化合物 2e 对受损的 ECV-304 细胞增殖表现出最高的保护作用（EC₅₀=0.020 mM），化合物 2f 是最有效的抗血小板聚集剂（EC₅₀=0.054 mM）。简要讨论了构效关系。