Inhibitors of the tyrosine kinase EphB4. Part 4: Discovery and optimization of a benzylic alcohol series

被引：29

作者：

Barlaam, Bernard ^{[1
]}

Ducray, Richard ^{[1
]}

Lambert-van der Brempt, Christine ^{[1
]}

Ple, Patrick ^{[1
]}

Bardelle, Catherine ^{[2
]}

Brooks, Nigel ^{[2
]}

Coleman, Tanya ^{[2
]}

Cross, Darren ^{[2
]}

Kettle, Jason G. ^{[2
]}

Read, Jon ^{[2
]}

机构：

[1] AstraZeneca, Ctr Rech, ZI Pompelle, F-51689 Reims 2, France

[2] AstraZeneca, Macclesfield SK10 4TG, Cheshire, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 08期

关键词：

EphB4; kinase; Kinase inhibitor; Bis-anilinopyrimidine; RECEPTOR; ANGIOGENESIS; DOMAIN;

D O I：

10.1016/j.bmcl.2011.03.009

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Optimization of our bis-anilino-pyrimidine series of EphB4 kinase inhibitors led to the discovery of compound 12 which incorporates a key m-hydroxymethylene group on the C4 aniline. 12 displays a good kinase selectivity profile, good physical properties and pharmacokinetic parameters, suggesting it is a suitable candidate to investigate the therapeutic potential of EphB4 kinase inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：2207 / 2211

页数：5

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