Biphenyl amide p38 kinase inhibitors 3: Improvement of cellular and in vivo activity

被引：64

作者：

Angell, Richard ^{[1
]}

Aston, Nicola M. ^{[1
]}

Bamborough, Paul ^{[1
]}

Buckton, Jacky B. ^{[1
]}

Cockerill, Stuart ^{[1
]}

deBoeck, Suzanne J. ^{[1
]}

Edwards, Chris D. ^{[1
]}

Holmes, Duncan S. ^{[1
]}

Jones, Katherine L. ^{[1
]}

Laine, Dramane I. ^{[1
]}

Patel, Shila ^{[1
]}

Smee, Penny A. ^{[1
]}

Smith, Kathryn J. ^{[1
]}

Somers, Don O. ^{[1
]}

Walker, Ann L. ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 15期

关键词：

p38; kinase; alpha; CSBP; MAP kinase; inhibitors; biphenyl amide; BPA; biphenyl amides; BPAs; protein kinase X-ray structure; binding mode; structure-based drug design; kinase selectivity; structure-activity relationships; PG-PS model; CIA model;

D O I：

10.1016/j.bmcl.2008.06.048

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The biphenyl amides (BPAs) are a novel series of p38 alpha MAP kinase inhibitor. The optimisation of the series to give compounds that are potent in an in vivo disease model is discussed. SAR is presented and rationalised with reference to the crystallographic binding mode. Published by Elsevier Ltd.

引用

页码：4428 / 4432

页数：5

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