Rational design and synthesis of selective BACE-1 inhibitors

被引：52
作者：
Brady, SF
Singh, S
Crouthamel, MC
Holloway, MK
Coburn, CA
Garsky, VM
Bogusky, M
Pennington, MW
Vacca, JP
Hazuda, D
Lai, MT [1 ]
机构：
[1] Merck Res Labs, Dept Biol Chem, W Point, PA 19486 USA
[2] Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
[3] Bachem Biosci Inc, King Of Prussia, PA 19406 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 03期
关键词：
D O I：
10.1016/j.bmcl.2003.11.061
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
An effective approach for enhancing the selectivity of beta-site amyloid precursor protein cleaving enzyme (BACE 1) inhibitors is developed based on the unique features of the S1' pocket of the enzyme. A series of low molecular weight ( < 600) compounds were synthesized with different moieties at the P1' position. The selectivity of BACE 1 inhibitors versus cathepsin D and renin was enhanced 120-fold by replacing the hydrophobic propyl group with a hydrophilic propionic acid group. (C) 2003 Elsevier Ltd. All rights reserved.
引用
收藏
页码：601 / 604
页数：4
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