The discovery of 2-amino-3,5-diarylbenzamide inhibitors of IKK-α and IKK-β kinases

被引：60

作者：

Christopher, John A.

Avitabile, Barbara G.

Bamborough, Paul

Champigny, Aurelie C.

Cutler, Geoffrey J.

Dyos, Susan L.

Grace, Ken G.

Kerns, Jeffrey K.

Kitson, Jeremy D.

Mellor, Geoffrey W.

Morey, James V.

Morse, Mary A.

O'Malley, Carolyn F.

Patel, Champa B.

Probst, Nicholas

Rumsey, William

Smith, Clive A.

Wilson, Michael J.

机构：

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

[2] GlaxoSmithKline R&D, Harlow CM19 5AW, Essex, England

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 14期

关键词：

kinase; IKK; inhibitor;

D O I：

10.1016/j.bmcl.2007.04.088

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A potent and selective series of 2-amino-3,5-diarylbenzamide inhibitors of IKK-alpha and IKK-beta is described. The most potent compounds are 8h, 8r and 8v, with IKK-beta inhibitory potencies of pIC(50) 7.0, 6.8 and 6.8, respectively. The series has excellent selectivity, both within the IKK family over IKK-epsilon, and across a wide variety of kinase assays. The potency of 8h in the IKK-beta enzyme assay translates to significant cellular activity (pIC(50) 5.7-6.1) in assays of functional and mechanistic relevance. (C) 2007 Elsevier Ltd. All rights reserved.

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收藏

页码：3972 / 3977

页数：6

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