Discovery of a novel [3.2.1] benzo fused bicyclic sulfonamide-pyrazoles as potent, selective and efficacious γ-secretase inhibitors

被引：10

作者：

Ye, Xiaocong M. ^{[1
]}

Konradi, Andrei W. ^{[1
]}

Sun, Minghua ^{[1
]}

Yuan, Shendong ^{[1
]}

Aubele, Danielle L. ^{[1
]}

Dappen, Michael ^{[1
]}

Dressen, Darren ^{[1
]}

Garofalo, Albert W. ^{[1
]}

Jagodzinski, Jacek J. ^{[1
]}

Latimer, Lee ^{[1
]}

Probst, Gary D. ^{[1
]}

Sham, Hing L. ^{[1
]}

Wone, David ^{[1
]}

Xu, Ying-zi ^{[1
]}

Ness, Daniel ^{[2
]}

Brigham, Elizabeth ^{[2
]}

Kwong, Grace T. ^{[2
]}

Willtis, Chris ^{[2
]}

Tonn, George ^{[3
]}

Goldbach, Erich ^{[3
]}

Quinn, Kevin P. ^{[3
]}

Zhang, Hongbin H. ^{[3
]}

Sauer, John-Michael ^{[3
]}

Bova, Michael ^{[4
]}

Basi, Guriqbal S. ^{[5
]}

机构：

[1] Elan Pharmaceut, Dept Med Chem, San Francisco, CA 94080 USA

[2] Elan Pharmaceut, Dept Pharmacol, San Francisco, CA 94080 USA

[3] Elan Pharmaceut, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA

[4] Elan Pharmaceut, Dept Assay Dev, San Francisco, CA 94080 USA

[5] Elan Pharmaceut, Dept Biol, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 04期

关键词：

Alzheimer's disease; Amyloid precursor protein; gamma-Secretase; gamma-Secretase inhibitor; Notch; ALZHEIMERS-DISEASE; GENES;

D O I：

10.1016/j.bmcl.2012.12.039

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Structure-activity relationship (SAR) of a novel, potent and metabolically stable series of benzo [3.2.1] bicyclic sulfonamide-pyrazoles as gamma-secretase inhibitors are described. Compounds that are efficacious in reducing the cortical A beta x-40 levels in FVB mice via oral dose, as well as those with high selectivity over Notch, are highlighted. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：996 / 1000

页数：5

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