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有机化学
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有机化学 ›› 2006, Vol. 26 ›› Issue (03): 318-323. 上一篇    下一篇

研究论文

替米沙坦及其类似物的合成和生物活性研究

余伟发1,2，周智明*,1，朱海波3，何令帅3   

  1. (1北京理工大学新药研究开发中心 北京 100081)
    (2中国石化股份有限公司石油化工科学研究院 北京 100083)
    (3中国医学科学院中国协和医科大学药物研究所 北京 100050)
  • 收稿日期:2005-01-27 修回日期:2005-09-15 发布日期:2006-02-28
  • 通讯作者: 周智明

Synthesis of Telmisartan and Its Derivatives and Evaluation of Their Biological Activities

YU Wei-Fa1,2,ZHOU Zhi-Ming*,1,ZHU Hai-Bo3,HE Ling-Shuai3   

  1. (1 Research & Development Center for Pharmaceuticals, Beijing Institute of Technology, Beijing 100081)
    (2 Research Institute of Petroleum Processing, China Petroleum & Chemical Corporation, Beijing 100083)
    (3 Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050)
  • Received:2005-01-27 Revised:2005-09-15 Published:2006-02-28
  • Contact: ZHOU Zhi-Ming

PDF

2864

被引次数

14

设计合成了替米沙坦及其类似物, 改进了替米沙坦的合成工艺. 用邻苯二胺与相应的有机羧酸缩合, 所得产物苯并咪唑衍生物与4'-溴甲基联苯-2-甲酸甲酯通过N-烷基化得到相应的目标化合物, 合成了替米沙坦和9种未见文献报道的苯并咪唑联苯化合物, 其结构经1H NMR, IR, MS和元素分析确证. 用体外动脉环的方法, 研究目标化合物的初步体外抗高血压活性, 试验结果表明其中部分化合物具有一定的抗高血压活性.

关键词: 非肽类血管紧张素II受体拮抗剂, 生物活性, 替米沙坦, 合成, 衍生物

The synthetic route of telmisartan and its derivatives was developed and improved. The condensation of o-phenylenediamine with various carboxylic acids gave benzimidazole derivatives, which were N-alkylated with methyl 4'-(bromomethyl)biphenyl-2-carboxylate to afford the corresponding title compounds. Nine novel title compounds were synthesized, and their structures were confirmed by 1H NMR, IR, MS spectra and elemental analyses. And the in vitro preliminary antihypertensive activity was evaluated by the method of aortic ring. Biological screening results dem-onstrated that some of the compounds displayed potential antihypertensive activity.

Key words: telmisartan, bioactivity, synthesis, derivative, angiotensin II receptor antagonist