Small-sized BACE1 inhibitors

被引：37

作者：

Ziora, Z ^{[1
]}

Kimura, T ^{[1
]}

Kiso, Y ^{[1
]}

机构：

[1] Kyoto Pharmaceut Univ, 21st Century COE Program, Ctr Frontier Res Med Sci, Dept Med Chem,Yamashina Ku, Kyoto 6078412, Japan

来源：

DRUGS OF THE FUTURE | 2006年 / 31卷 / 01期

关键词：

D O I：

10.1358/dof.2006.031.01.957326

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The determination of the three-dimensional X-ray crystal structure of beta-secretase (BACE) complexed with an inhibitor has greatly facilitated the design of BACE inhibitors. Generally, BACE inhibitors can be grouped into two main families: substrate-based inhibitors designed as peptidomimetic inhibitors and nonpeptidomimetic inhibitors. This review focuses on the rational design of inhibitors based on transition-state analogues. The structural nature of peptidomimetic inhibitors usually implies relatively poor catabolic stability and low bioavailability after systemic administration due to low blood-brain barrier permeability. To overcome these drawbacks, several different approaches have been used.

引用

页码：53 / 63

页数：11

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