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

页码：4711 / 4714

页数：4

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