Discovery of 6-Aryl-7-alkoxyisoquinoline Inhibitors of IκB Kinase-β (IKK-β)

被引：30

作者：

Christopher, John A. ^{[1
]}

Bamborough, Paul ^{[1
]}

Alder, Catherine ^{[1
]}

Campbell, Amanda ^{[1
]}

Cutler, Geoffrey J. ^{[2
]}

Down, Kenneth ^{[1
]}

Hamadi, Ahmed M. ^{[1
]}

Jolly, Adrian M. ^{[1
]}

Kerns, Jeffrey K. ^{[3
]}

Lucas, Fiona S. ^{[1
]}

Mellor, Geoffrey W. ^{[2
]}

Miller, David D. ^{[1
]}

Morse, Mary A. ^{[1
]}

Pancholi, Kiritkant D. ^{[2
]}

Rumsey, William ^{[3
]}

Solanke, Yemisi E. ^{[1
]}

Williamson, Rick ^{[1
]}

机构：

[1] GlaxoSmithKline R&D, Med Res Ctr, Stevenage SG1 2NY, Herts, England

[2] GlaxoSmithKline R&D, Essex, England

[3] GlaxoSmithKline Inc, King Of Prussia, PA 19406 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 09期

关键词：

CELL-CYCLE; ALPHA;

D O I：

10.1021/jm9000117

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The identification and progression of a potent and selective series of isoquinoline inhibitors of I kappa B kinase-beta (IKK-beta) are described. Hit-generation chemistry based on IKK-beta active-site knowledge yielded a weakly potent but tractable chemotype that was rapidly progressed into a series with robust enzyme and cellular activity and significant selectivity over IKK-alpha.

引用

页码：3098 / 3102

页数：5

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