Design and synthesis of BACE-1 inhibitors utilizing a tertiary hydroxyl motif as the transition state mimic

被引：12
作者：
Wangsell, Fredrik [1 ]
Russo, Francesco [1 ]
Savmarker, Jonas [1 ]
Rosenquist, Asa [2 ,3 ]
Samuelsson, Bertil [3 ,4 ]
Larhed, Mats [1 ]
机构：
[1] Uppsala Univ, Dept Med Chem, BMC, SE-75123 Uppsala, Sweden
[2] Linkoping Univ, Dept Chem, SE-58183 Linkoping, Sweden
[3] Medivir AB, SE-14144 Huddinge, Sweden
[4] Stockholm Univ, Arrhenius Lab, Dept Organ Chem, SE-10691 Stockholm, Sweden
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 16期
基金：
瑞典研究理事会;
关键词：
Alzheimer's disease; BACE-1; Enzyme inhibitor; Transition state mimetic; HIV-1 PROTEASE INHIBITORS; ALZHEIMERS-DISEASE; BETA-SECRETASE; ALCOHOL; POTENT;
D O I：
10.1016/j.bmcl.2009.06.065
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Two series of drug-like BACE-1 inhibitors with a shielded tertiary hydroxyl as transition state isostere have been synthesized. The most potent inhibitor exhibited a BACE-1 IC50 value of 0.23 mu M. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4711 / 4714
页数：4
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