Thienopyridine ureas as dual inhibitors of the VEGF and Aurora kinase families
Thienopyridine ureas as dual inhibitors of the VEGF and Aurora kinase families
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DOI：
10.1016/j.bmcl.2012.03.035
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发表时间：
2012-05-01
影响因子：
2.7
通讯作者：
Michaelides, Michael R.
中科院分区：
文献类型：
--
作者：
Curtin, Michael L.;Frey, Robin R.;Michaelides, Michael R.
为了鉴定具有新激酶活性谱的多靶点激酶抑制剂，对雅培专利的KDR抑制剂进行了广泛的激酶筛选，并发现了一系列具有抗极光激酶活性的噻吩吡啶脲。对这些化合物的二苯基尿素和C7部分进行修饰，提供了有效的抑制剂，具有良好的药代动力学特征，口服给药后在小鼠肿瘤模型中有效。该系列的化合物2 （ABT-348）目前正在实体癌和血液病人群中进行I期临床试验。(C) 2012 Elsevier Ltd.版权所有。
In an effort to identify multi-targeted kinase inhibitors with a novel spectrum of kinase activity, a screen of Abbott proprietary KDR inhibitors against a broad panel of kinases was conducted and revealed a series of thienopyridine ureas with promising activity against the Aurora kinases. Modification of the diphenyl urea and C7 moiety of these compounds provided potent inhibitors with good pharmacokinetic profiles that were efficacious in mouse tumor models after oral dosing. Compound 2 (ABT-348) of this series is currently undergoing Phase I clinical trials in solid and hematological cancer populations. (C) 2012 Elsevier Ltd. All rights reserved.