The discovery of substituted 4-(3-hydroxyanilino)-quinolines as potent RET kinase inhibitors

被引：23
|
作者：
Robinett, R. Graham
Freemerman, Alex J.
Skinner, Michael A.
Shewchuk, Lisa
Lackey, Karen
机构：
[1] GlaxoSmithKline Inc, Mol Discovery Res Chem, Res Triangle Pk, NC 27709 USA
[2] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 21期
关键词：
c-src; RET; kinase inhibitors; 4-anilinoquinolines;
D O I：
10.1016/j.bmcl.2007.07.104
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Substituted 4-(3-hydroxyanilino)-quinoline compounds, initially identified as small-molecule inhibitors of src family kinases, have been evaluated as potential inhibitors of RET kinase. Three compounds, 38, 31, and 40, had K-i's of 3, 25, and 50 nM in an in vitro kinase assay; while a cell based kinase assay showed Ki's of 300, 100, and 45 nM, respectively. These compounds represent potential new leads for the treatment of medullary and papillary thyroid cancer. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5886 / 5893
页数：8
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