L-酒石酸衍生物的合成及其抑制β-分泌酶活性  

Synthesis of L-tartaric acid derivatives as novel inhibitors of BACE1

作　　者：廖国超[1] 聂爱华[1] 钟武[1] 李松[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药物化学杂志》2008年第6期406-413,共8页Chinese Journal of Medicinal Chemistry

摘　　要：目的设计并合成β-分泌酶(BACE1)的小分子抑制剂。方法基于BACE1的晶体结构及其配体的关键结构特征,设计并合成新结构的BACE1配体;通过荧光共振能量转移(FRET)法检测化合物抑制BACE1的水解活性。结果与结论合成了26个酒石酸衍生物。筛选结果表明,部分化合物对BACE1有一定的抑制作用。Aim To design and synthesize novel non-peptidic L-tartaric acid derivatives as inhibitors of BACE1. Methods According to the crystal structure of BACE1 and the critical structure of OM99-2, CADD （computer-aided drug design） was employed to design and virtual screen the novel L-tartaric acid derivatives. These compounds were synthesized by liquid-phase synthetic method. Results and conclusion 26 Target compounds were synthesized. Some of these compounds were demonstrated to bind to BACE1 by using a fluorescence resonance energy transfer （FRET） assay. Compound 6f exhibited BACE1 inhibitory activity in vitro with the IC50 of 7.30μmol· L^- 1.

关 键 词：设计 合成 Β-分泌酶抑制剂 老年痴呆症 

分 类 号：R914[医药卫生—药物化学]