乙酰水杨酰阿魏酸与呋咱氮氧化物和硝酸酯偶联物的合成及其抗血栓作用  

Synthesis and antithrombotic activity of acetylsalicyl ferulic acid-coupling furoxans and nitrates

作　　者：周洲[1] 蒋丽媛[1] 张奕华[1] 季晖[2] 孙易[2] 彭司勋[1] 

机构地区：[1]中国药科大学新药研究中心,江苏南京210009 [2]中国药科大学药理学教研室,江苏南京210009

出　　处：《药学学报》2006年第11期1050-1056,共7页Acta Pharmaceutica Sinica

摘　　要：目的研究NO供体型阿司匹林衍生物的合成和抗血栓活性,寻找新型抗血栓药物。方法阿司匹林经阿魏酸分别与呋咱氮氧化物和硝酸酯连接得到目标化合物;通过体外、体内血小板聚集试验和大鼠动静脉旁路血栓试验对新化合物进行抗血栓作用初筛。结果合成了14个新化合物I1-14,其结构经MS,IR,1H NMR和元素分析确证;药理初筛结果表明,部分化合物在体内、体外均显示出较好的抗血栓活性。结论乙酰水杨酰阿魏酸与呋咱氮氧化物和硝酸酯偶联物可作为抗血栓先导物,值得深入研究。Aim To synthesize and study the antithrombotic activity of NO-donating aspirin derivatives. Methods Furoxans and nitrates were incorporated to aspirin via antioxidant ferulic acid as a linker, and the target compounds were screened for in vitro and in vivo inhibitory activities of platelet aggregation, and for inhibitory effect on A-V bypass thrombosis in rats. Results Fourteen novel compounds I1-14 were synthesized and their structures were confirmed by MS, IR, ^1H NMR and elemental analysis. Biological screening results demonstrated that some tested compounds exhibited potential antithrombotic activity. Conclusion Acetylsalicyl ferulic acid -coupling furoxans and nitrates might be used as a lead for further study.

关 键 词：乙酰水杨酰阿魏酸 呋咱氮氧化物 硝酸酯 NO供体 阿司匹林 合成 抗血栓活性 

分 类 号：R916.41[医药卫生—药学]