香豆素硝酸酯类衍生物的合成及抗血小板聚集活性

Synthesis and Anti-Platelet Aggregation Activities of Coumarin Nitrate Derivatives

以间苯二酚与乙酰乙酸乙酯为原料制备4-甲基-7-羟基香豆素,利用其7位羟基与二溴烷烃反应得到4-甲基-7-溴烷氧基香豆素,再将其与硝酸银反应得到5个香豆素硝酸酯类衍生物。目标化合物经红外光谱、核磁共振氢谱、质谱表证。体外抗血小板聚集活性测试结果表明,化合物4-甲基-7-硝氧烷氧基香豆素(4a^4e)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,其IC_(50)值为0.012~0.046mmol,强于阳性对照药阿司匹林(IC_(50)值为0.052mmol)。

4-Methyl-7-hydroxy-coumarin was obtained by the reaction between resorcinol and ethyl acetoacetate followed by treating with dibromoalkanes（2~6 carbons）in the presence of K2CO3 to provide the compounds 4-methyl-7-bromoalkoxy-coumarin（3 a^3 e）,these compounds were then reacted with silver nitrate to give the target compounds 4-methyl-7-nitroxylcoumarin（4 a^4 e）.The chemical structure of target compounds was confirmed by IR,^1H NMR,and MS.Anti-platelet aggregation activities of target compounds were assayed in vitro and the results demonstrates that all target compounds exhibit antiplatelet aggregation activities.Compounds 4 a^4 eshow significant anti-platelet aggregation activities with IC50 values ranging from 0.012 to 0.046 mmol,which are 2-to 4-fold better than that of the control of aspirin（IC50=0.052 mmol）.