Discovery of a novel sulfonamide-pyrazolopiperidine series as potent and Efficacious γ-Secretase Inhibitors

被引：15

作者：

Ye, Xiaocong M. ^{[1
]}

Konradi, Andrei W. ^{[1
]}

Smith, Jenifer ^{[1
]}

Xu, Ying-Zi ^{[1
]}

Dressen, Darren ^{[1
]}

Garofalo, Albert W. ^{[1
]}

Marugg, Jennifer ^{[1
]}

Sham, Hing L. ^{[1
]}

Truong, Anh P. ^{[1
]}

Jagodzinski, Jacek ^{[2
]}

Pleiss, Michael ^{[1
]}

Zhang, Hongbin ^{[3
]}

Goldbach, Erich ^{[3
]}

Sauer, John-Michael ^{[3
]}

Brigham, Elizabeth ^{[4
]}

Bova, Michael ^{[5
]}

Basi, Guriqbal S. ^{[5
]}

机构：

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

[2] Elan Pharmaceut, Dept Proc & Analyt Chem, San Francisco, CA 94080 USA

[3] Elan Pharmaceut, Dept Lead Discovery & Optimizat, San Francisco, CA 94080 USA

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

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 07期

关键词：

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

D O I：

10.1016/j.bmcl.2010.02.039

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Discovery of a series of pyrazolopiperidine sulfonamide based gamma-secretase inhibitors and its SAR evolution is described. Significant increases in APP potency on the pyrazolopiperidine scaffold over the original N-bicyclic sulfonamide scaffold were achieved and this potency increase translated in an improved in vivo efficacy. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：2195 / 2199

页数：5

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