7-硝氧烷氧基-3-乙酰基香豆素的合成及抗血小板聚集活性  

Synthesis and Anti-Platelet Aggregation Activity of 7-Nitratoalkoxyl-3-acetyl-coumarin

作　　者：尚飞扬 戴卫国 何冰 何黎琴 Shang Feiyang;Dai Weiguo;He Bing;He Liqin(College of Pharmacy,Anhui University of Chinese Medicine,Hefei,Anhui 230038,China)

机构地区：[1]安徽中医药大学药学院,安徽合肥230038

出　　处：《化学世界》2022年第1期17-21,共5页Chemical World

基　　金：安徽省教育厅自然科学重点科研(No.KJ2020A0957)资助项目。

摘　　要：以间苯二酚为起始原料,经Vilsmeier-Haack反应、Knoevenagel反应得到7-羟基-3-乙酰基香豆素(3),再利用其7位羟基通过连接臂与有机硝酸酯类NO供体耦合,得到5个7-硝氧烷氧基-3-乙酰基香豆素(5a~5e)。目标化合物经过红外光谱(IR)、核磁共振氢谱(;H NMR)和高分辨质谱(HRMS)表征。采用Born比浊法,以二磷酸腺苷(ADP)和胶原为诱导剂,对目标化合物5a~5e进行了的体外抗血小板聚集的活性试验,结果表明,目标化合物5a~5e对ADP和胶原诱导的血小板聚集具有一定的抑制作用,化合物5d的抗血小板聚集作用最强,明显优于阳性对照药阿司匹林。7-Hydroxy-3-acetyl-coumarin was obtained from resorcinol by Vilsmeier-Haack and Knoevenagel reactions, which was then treated with dibromoalkanes(2~6 carbons) in the presence of K;CO;to provide 7-bromoalkoxyl-3-acetyl-coumarin(4 a~4 e). Compounds 4 a~4 e reacted with silver nitrate to give the target compounds of 7-nitratoalkoxyl-3-acetyl-coumarin(5 a~5 e). Their structures were confirmed by IR,;H NMR and high-resolution mass spectrometry(HRMS). The anti-platelet aggregation activity of 5 a~5 e was tested by Born turbidimetry using adenosine diphosphate(ADP) and collagen as inducers. It was found that the synthesized compounds had inhibitory effects on both ADP and collagen-induced platelet aggregations. Compound 5 d exhibited excellent activity than the reference drug aspirin.

关 键 词：7-羟基-3-乙酰基香豆素 硝酸酯 抗血小板聚集 

分 类 号：R916[医药卫生—药学]