香豆素-3-羧酸乙酯衍生物的合成及抗血小板聚集活性

Synthesis and Anti-platelet Aggregation Activity of Ethyl Coumarin-3-carboxylate Derivatives

以间二苯酚为原料,经Vilsmeier-Haack,Knoevenagel等反应得到7-羟基香豆素-3-羧酸乙酯(3),利用其7位羟基与不同碳数的二溴烷烃反应得到7-溴代烷氧基-香豆素-3-羧酸乙酯(4a～4e),再将其与硝酸银反应得到7-硝氧烷氧基香豆素-3-羧酸乙酯(5a～5e)。化合物5a～5e经过红外光谱、核磁共振氢谱和质谱表证。体外抗血小板聚集活性测试结果表明,所得目标化合物对二磷酸腺苷(ADP)所诱导的血小板聚集均具有较强的抑制活性,抑制率达32.86%～40.71%,强于阳性对照药阿司匹林(19.33%)。

7-hydroxycoumarin-3-carboxylate (3) was synthesized from reaction by Vilsmeier-Haack and Knoevenagel reaction.Compound 3 reacted with dibromoalkanes (2.6 carbons) in the presence of K2CO3 to gain the compounds 7-bromoalkoxy-coumarin-3-carboxylate (4a^4e).These compounds reacted with silver nitrate to give the target compounds 7-nitroxyl alkoxy-coumarin-3-carboxylate (5a^5e).The chemical structure of target compounds was confirmed by IR,^1 H NMR,and MS.Anti-platelet aggregation activities of target compounds were assayed in vitro and the results demonstrates that all target compounds exhibit stronger anti-platelet aggregation activities (AIR: 32.86%.40.71%) than aspirin (AIR: 19.33%).