3-芳基-1，2，3，4-噁三唑-5-亚胺与阿司匹林偶联物的合成和抗血栓活性研究  

Synthesis and Antithrombotic Activity of 3-Aryl-1,2,3,4-oxatriazole-5-imine-Coupled Aspirin

作　　者：周洲[1] 赖宜生[1] 张奕华[1] 季晖[2] 李立文[2] 彭司勋[1] 

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

出　　处：《有机化学》2008年第5期819-824,共6页Chinese Journal of Organic Chemistry

摘　　要：取代苯胺经重氮化、还原得苯肼盐酸盐,与硫氰酸钾作用得苯基取代的氨基硫脲,再在亚硝酸异戊酯、盐酸的作用下环合、成盐,加碱中和后生成3-芳基-1,2,3,4-噁三唑-5-亚胺,最后与乙酰水杨酰氯反应得目标物6a～6l,其结构经MS,IR,1H NMR和元素分析确证.体外血小板聚集试验和小鼠肺血栓生成试验结果表明,部分目标物在体内、外均显示出较好的抗血栓活性,值得深入进行研究.Substituted aniline was diazotized and subsequently reduced to give phenylhydrazine hydrochloride, which reacted with potassium thiocyanate to produce aryl-substituted thiosemicarbazide, followed by reaction with isopentyl nitrite and hydrochloric acid and neutralization with alkali to afford 3-aryl-1,2,3,4- oxatriazole-5-imine. The imine obtained finally was coupled with aspirin to give target compounds 6a-6l. The structures of all compounds were identified by MS, IR, ^1H NMR spectra and elemental analysis. The in vitro inhibitory activities against platelet aggregation in rats and in vivo inhibitory effect on pulmonary thrombus formation in mice were investigated. The preliminary results showed that some tested compounds exhibited potential antithrombotic activity and deserve further study.

关 键 词：3-芳基-1 2 3 4-噁三唑-5-亚胺 阿司匹林 NO供体 抗血栓活性 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]