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有机化学
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有机化学 ›› 2008, Vol. 28 ›› Issue (12): 2170-2174. 上一篇    下一篇

研究简报

胆汁酸为载体的肝靶向一氧化氮释放药物的设计与合成

李美英 ; 何新华; 陶 林; 刘 河* ; 李宏武; 仲伯华*   

  1. (军事医学科学院毒物药物研究所 北京 100850)
  • 收稿日期:2008-03-29 修回日期:2008-05-20 发布日期:2008-12-28
  • 通讯作者: 刘 河;仲伯华

Design and Synthesis of Liver Targeted NO-Releasing Drugs with Bile Acids as Carriers

LI, Mei-Ying ; HE, Xin-Hua; TAO, Lin LIU, He*;LI, Hong-Wu; ZHONG, Bo-Hua*
  

  1. (Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, PLA, Beijing 100850)
  • Received:2008-03-29 Revised:2008-05-20 Published:2008-12-28
  • Contact: LIU, He*;ZHONG, Bo-Hua*

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1639

被引次数

11 | 1

新型肝靶向一氧化氮释放药物对许多肝脏疾病具有较好的治疗作用. 以胆酸和熊去氧胆酸作为药物的载体, 以氨基酸作为联接子, 以氨基酸的α羧基模拟胆酸或熊去氧胆酸分子24位羧基的负电性, 最大限度地保持胆酸或熊去氧胆酸的结构特征, 通过酰胺键将载体与一氧化氮供体硝酸酯偶联, 设计并合成了一系列新型肝靶向一氧化氮释放偶合物, 其结构经元素分析, IR, 1H NMR和MS光谱分析确证. 利用四氯化碳及对乙酰氨基酚所致小鼠急性肝损伤模型研究化合物对小鼠急性肝损伤的修复作用.

关键词: 胆酸, 靶向药物, 一氧化氮释放药物

New liver targeted NO-releasing drugs can effectively repair liver damage. A series of novel liver targeted NO-releasing conjugates were designed and synthesized by conjugating the nitrated amino acids with the carboxyl group of cholic acid or ursodeoxycholic acid. The chemical structures of all new conjugates and intermediates were confirmed by elemental analysis, IR, 1H NMR and MS techniques. Their repairing activities to mice acute liver damage induced by acetaminophen and carbon tetrachloride were investigated.

Key words: bile acid, targeted drug, nitric oxide-releasing drug