胆汁酸为载体的肝靶向一氧化氮释放药物的设计与合成

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.

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

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 ac-ids with the carboxyl group of cholic acid or ursodeoxycholic acid.The chemical structures of all new con-jugates and intermediates were confirmed by elemental analysis,IR,1H NMR and MS techniques.Their re-pairing activities to mice acute liver damage induced by acetaminophen and carbon tetrachloride were inves-tigated.