SAR and inhibitor complex structure determination of a novel class of potent and specific Aurora kinase inhibitors
SAR and inhibitor complex structure determination of a novel class of potent and specific Aurora kinase inhibitors
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DOI：
10.1016/j.bmcl.2005.11.053
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发表时间：
2006-03-01
影响因子：
2.7
通讯作者：
Rowsell, S
中科院分区：
文献类型：
--
作者：
Heron, NM;Anderson, M;Rowsell, S
在Aurora A的高通量筛选中，从苯胺基-喹唑啉1开发了一系列新的5-氨基嘧啶基喹唑啉，它被鉴定为Aurora A。嘧啶环的引入以及对该环上和喹唑啉C7位的取代基的优化导致了高度专一性的Aurora激酶抑制剂的化合物的发现。其中一种抑制剂与Aurora A片段的共结晶表明了苯甲酰胺基团在实现选择性方面的重要性。(C)2005爱思唯尔有限公司。保留所有权利。
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.