Discovery of a novel series of Notch-sparing γ-secretase inhibitors

被引：20

作者：

Kreft, Anthony ^{[1
]}

Harrison, Boyd ^{[1
]}

Aschmies, Suzan ^{[2
]}

Atchison, Kevin ^{[2
]}

Casebier, David ^{[4
]}

Cole, Derek C. ^{[1
]}

Diamantidis, George ^{[1
]}

Ellingboe, John ^{[1
]}

Hauze, Diane ^{[1
]}

Hu, Yun ^{[2
]}

Huryn, Donna ^{[1
]}

Jin, Mei ^{[2
]}

Kubrak, Dennis ^{[1
]}

Lu, Peimin ^{[2
]}

Lundquist, Joseph ^{[1
]}

Mann, Charles ^{[1
]}

Martone, Robert ^{[2
]}

Moore, William ^{[4
]}

Oganesian, Aram ^{[3
]}

Porte, Alex ^{[1
]}

Riddell, Dave R. ^{[2
]}

Sonnenberg-Reines, June ^{[2
]}

Stock, Joseph R. ^{[1
]}

Sun, Shaiu-Ching ^{[2
]}

Wagner, Erik ^{[2
]}

Woller, Kevin ^{[4
]}

Xu, Zheng ^{[2
]}

Zhou, Hua ^{[2
]}

Jacobsen, J. Steven ^{[2
]}

机构：

[1] Wyeth Ayerst Res, Chem & Screening Sci, Princeton, NJ 08543 USA

[2] Wyeth Ayerst Res, Discovery Neurosci, Princeton, NJ 08543 USA

[3] Wyeth Ayerst Res, Drug Safety & Metab, Collegeville, PA 19426 USA

[4] ArQule Inc, Woburn, MA 01801 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 14期

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; gamma-secretase; Notch; amyloid; protease inhibitor;

D O I：

10.1016/j.bmcl.2008.05.064

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Using a cell-based assay, we have identified a new series of Notch-sparing gamma-secretase inhibitors from HTS screening leads 2a and 2e. Lead optimization studies led to the discovery of analog 8e with improved gamma-secretase inhibitory potency and Notch-sparing selectivity. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4232 / 4236

页数：5

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