Chin. J. Org. Chem. ›› 2008, Vol. 28 ›› Issue (05): 819-824. Previous Articles     Next Articles

Original Articles

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

周洲a,赖宜生a,张奕华*,a,季晖*,b,李立文b,彭司勋a   

  1. (a中国药科大学新药研究中心 南京 210009)
    (b中国药科大学药理学教研室 南京 210009)
  • 收稿日期:2007-06-07 修回日期:2007-10-16 发布日期:2008-05-20
  • 通讯作者: 张奕华

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

ZHOU Zhoua,LAI Yi-Shenga,ZHANG Yi-Hua*,a,JI Hui*,b
LI Li-Wenb,PENG Si-Xuna   

  1. (a Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009)
    (b Department of Pharmacology, China Pharmaceutical University, Nanjing 210009)
  • Received:2007-06-07 Revised:2007-10-16 Published:2008-05-20
  • Contact: ZHANG Yi-Hua

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 6a6l. The structures of all compounds were identified by MS, IR, 1H NMR spectra and elemental analysis. The in vitro inhibitory activities against plate-let 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.

Key words: aspirin, NO donor, antithrombotic activity, 3-aryl-1,2,3,4-oxatriazole-5-imine