Dual EGFR/ErbB-2 inhibitors from novel pyrrolidinyl-acetylenic thieno[3,2-d] pyrimidines

被引：36

作者：

Hubbard, Robert D. ^{[1
]}

Dickerson, Scott H. ^{[1
]}

Emerson, Holly K. ^{[1
]}

Griffin, Robert J. ^{[1
]}

Reno, Michael J. ^{[1
]}

Hornberger, Keith R. ^{[1
]}

Rusnak, David W. ^{[1
]}

Wood, Edgar R. ^{[1
]}

Uehling, David E. ^{[1
]}

Waterson, Alex G. ^{[1
]}

机构：

[1] GlaxoSmithKline Res & Dev Ltd, Res Triangle Pk, NC 27709 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 21期

关键词：

Epidermal growth factor receptor; EGFR; ErbB-2; Inhibitor; Thieno[3,2-d] pyrimidines;

D O I：

10.1016/j.bmcl.2008.09.090

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of substituted pyrrolidinyl-acetylenic thieno[3,2-d] pyrimidines has been identified that are potent and selective inhibitors of both EGFR/ErbB-2 receptor tyrosine kinases. The inhibitors are found to display a range of enzyme and cellular potency and also to display a varying level of covalent modi. cation of the kinase targets. Selected molecules, including compound 15h, were found to be potent in enzymatic and cellular assays while also demonstrating exposure in the mouse from an oral dose. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5738 / 5740

页数：3

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