Design, synthesis, and structure-activity relationship studies of N-arylsulfonyl morpholines as γ-secretase inhibitors

被引：15

作者：

Li, Hongmei ^{[1
]}

Xu, Ruo ^{[1
]}

Cole, David ^{[1
]}

Clader, John W. ^{[1
]}

Greenlee, William J. ^{[1
]}

Nomeir, Amin A. ^{[2
]}

Song, Lixin ^{[3
]}

Zhang, Lili ^{[3
]}

机构：

[1] Merck Res Lab, Dept Chem Res, Kenilworth, NJ 07033 USA

[2] Merck Res Lab, Dept Drug Safety & Metab, Kenilworth, NJ 07033 USA

[3] Merck Res Lab, Dept Neurobiol, Kenilworth, NJ 07033 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 22期

关键词：

gamma-Secretase inhibitors; Alzheimer's disease; ALZHEIMERS-DISEASE; UNITED-STATES; DISCOVERY; PIPERIDINES; HYPOTHESIS;

D O I：

10.1016/j.bmcl.2010.09.028

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Design and synthesis of cis-2,6-disubstituted N-arylsulfonyl morpholines as novel gamma-secretase inhibitors for the potential treatment of Alzheimer's disease (AD) is reported. Several different small alkyl groups are installed on the left-hand side to lower the CYP3A4 liability while maintaining excellent in vitro potency. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：6606 / 6609

页数：4

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