Synthesis and evaluation of aniline headgroups for alkynyl thienopyrimidine dual EGFR/ErbB-2 kinase inhibitors

被引：49

作者：

Waterson, Alex G. ^{[1
]}

Petrov, Kimberly G. ^{[1
]}

Hornberger, Keith R. ^{[1
]}

Hubbard, Robert D. ^{[1
]}

Sammond, Douglas M. ^{[1
]}

Smith, Stephon C. ^{[1
]}

Dickson, Hamilton D. ^{[1
]}

Caferro, Thomas R. ^{[1
]}

Hinkle, Kevin W. ^{[1
]}

Stevens, Kirk L. ^{[1
]}

Dickerson, Scott H. ^{[1
]}

Rusnak, David W. ^{[1
]}

Spehar, Glenn M. ^{[1
]}

Wood, Edgar R. ^{[1
]}

Griffin, Robert J. ^{[1
]}

Uehling, David E. ^{[1
]}

机构：

[1] GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 05期

关键词：

Kinase inhibitor; EGFR; ErbB-2; Medicinal chemistry; RECEPTOR TYROSINE KINASE; ORALLY-ACTIVE INHIBITORS; GROWTH-FACTOR RECEPTOR; 5-SUBSTITUTED; 4-ANILINOQUINAZOLINES; IRREVERSIBLE INHIBITOR; CANCER; EGFR; POTENT;

D O I：

10.1016/j.bmcl.2009.01.080

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Aniline 'headgroups' were synthesized and incorporated into an alkynyl thienopyrimidine series of EGFR and ErbB-2 inhibitors. Potent inhibition of enzyme activity and cellular proliferation was observed. In certain instances, protein binding was reduced and oral exposure was found to be somewhat improved relative to compounds containing the reference aniline. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1332 / 1336

页数：5

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