醛糖还原酶抑制剂Fidarestat衍生物的合成与生物活性.doc

文档介绍：醛糖还原酶抑制剂Fidarestat衍生物的合成与生物活性
段瑞平,王栋,朱长进收稿日期:2008 - 9 -
作者简介:段瑞平(1984—),女,硕士研究生
*通讯作者:朱长进(1958—),男,教授,E-mail: ******@bit.
(北京理工大学化工与环境学院,北京,100081)
摘要:目的开发一系列更为有效的醛糖还原酶抑制剂(ARIs)。方法 Fidarestat是一个非常有潜力的ARIs,本文基于Fidarestat的结构,经过C-2位修饰,设计并合成了一系列新的ARIs。结果当C-2位修饰氢键给体基团羟基时最有效(所合成的化合物4抑制性最强,IC50 = µM)。结论新的ARIs可以通过改变Fidarestat的C-2位取代基的方法设计合成。
关键词:醛糖还原酶抑制剂;fidarestat衍生物;合成;生物活性
Synthesis and Bioactivity of Aldose Reductase Inhibitor Fidarestat Derivatives
DUAN Rui-ping, WANG Dong, ZHU Chang-jin
(School of Chemical Engineering and Environment , Beijing Institute of Technology , Beijing 100081 , China)
Abstract: Objective A series of more effective ARIs have been developed. Methods Fidarestat was reported to have more potent and beneficial effects on sorbitol accumulation and diabetic neuropathy. A series of derivatives modified at C-2 position have been designed and synthesized which are based on the structure of Fidarestat. Results pound possessing substituent with a terminal hydroxyl group on the carbamoyl at C-2 position showed the most significant inhibition activity (compound 4, IC50 = μM). Conclusion The new ARIs can be designed and synthesized by the method of modifying at C-2 position of Fidarestat.
Key words: aldose reductase inhibitors; Fidarestat derivatives; synthesis; bioactivity
随着世界人口的老龄化,糖尿病(diabetes mellitus,DM)已经成为一种常见病、多发病,而持续的糖尿病将引起多种慢性并发症。尽管糖尿病并发症的机