Progress in the Development of Nonpeptidomimetic BACE 1 Inhibitors for Alzheimer's Disease

被引:57
|
作者
Huang, Wen-Hai [1 ]
Sheng, Rong [1 ]
Hu, Yong-Zhou [1 ]
机构
[1] Zhejiang Univ, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Hangzhou 310058, Zhejiang, Peoples R China
关键词
Alzheimer's disease (AD); nonpeptidomimetic inhibitors; BACE; 1; inhibitor; BETA-SECRETASE INHIBITORS; AMYLOID PRECURSOR PROTEIN; STRUCTURE-BASED DESIGN; X-RAY CRYSTALLOGRAPHY; MACROCYCLIC INHIBITORS; ASPARTYL PROTEASE; CRYSTAL-STRUCTURE; GAMMA-SECRETASE; HUMAN BRAIN; DISCOVERY;
D O I
10.2174/092986709788186174
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
It is believed that the production and accumulation of beta-amyloid (A beta) peptide is a critical step to the pathogenesis of Alzheimer's disease (AD). BACE 1 (beta-site APP-cleaving enzyme 1 or beta-secretase), the key enzyme required for generating A beta from the beta-amyloid precursor protein (APP), is regarded as an ideal target for AD therapeutic drug design. Due to low oral bioavailability, metabolic instability and poor ability to penetrate the central nervous system (CNS) of the existing peptidomimetic inhibitors, researchers have paid more attention to the development of nonpeptidomimetic inhibitors in recent years. A number of drug screening approaches and technologies have been used to identify novel nonpeptidomimetic BACE 1 inhibitors. This review mainly focuses on the recent developments in structure-based design and synthesis of the nonpeptidomimetic BACE 1 inhibitors.
引用
收藏
页码:1806 / 1820
页数:15
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