SAR and inhibitor complex structure determination of a novel class of potent and specific Aurora kinase inhibitors

被引：112

作者：

Heron, NM

Anderson, M

Blowers, DP

Breed, J

Eden, JM

Green, S

Hill, GB

Johnson, T

Jung, FH

McMiken, HHJ

Mortlock, AA

Pannifer, AD

Pauptit, RA

Pink, J

Roberts, NJ

Rowsell, S

机构：

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

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 05期

关键词：

aurora kinases; kinase inhibitor; anilino-quinazoline; protein kinase inhibition;

D O I：

10.1016/j.bmcl.2005.11.053

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of 5-aminopyrimidinyl quinazolines has been developed from anilino-quinazoline 1, which was identified in a high throughput screen for Aurora A. Introduction of the pyrimidine ring and optimisation of the substituents both on this ring and at the C7 position of the quinazoline led to the discovery of compounds that are highly specific Aurora kinase inhibitors. Co-crystallisation of one of these inhibitors with a fragment of Aurora A shows the importance of the benzamido group in achieving selectivity. (C) 2005 Elsevier Ltd. All rights reserved.

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页码：1320 / 1323

页数：4

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