Discovery of 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine inhibitors of Erk2

被引：29

作者：

Blake, James F. ^{[1
]}

Gaudino, John J. ^{[1
]}

De Meese, Jason ^{[1
]}

Mohr, Peter ^{[1
]}

Chicarelli, Mark ^{[1
]}

Tian, Hongqi ^{[1
]}

Garrey, Rustam ^{[1
]}

Thomas, Allen ^{[1
]}

Siedem, Christopher S. ^{[1
]}

Welch, Michael B. ^{[1
]}

Kolakowski, Gabrielle ^{[1
]}

Kaus, Robert ^{[1
]}

Burkard, Michael ^{[1
]}

Martinson, Matthew ^{[1
]}

Chen, Huifen ^{[2
]}

Dean, Brian ^{[2
]}

Dudley, Danette A. ^{[2
]}

Gould, Stephen E. ^{[2
]}

Pacheco, Patricia ^{[2
]}

Shahidi-Latham, Sheerin ^{[2
]}

Wang, Weiru ^{[2
]}

West, Kristina ^{[2
]}

Yin, Jianping ^{[2
]}

Moffat, John ^{[2
]}

Schwarz, Jacob B. ^{[2
]}

机构：

[1] Array BioPharma Inc, Boulder, CO 80301 USA

[2] Genentech Inc, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 12期

关键词：

Erk2 kinase inhibitors; Mek resistance; Structure based drug design; KINASE SIGNALING PATHWAYS; CANCER;

D O I：

10.1016/j.bmcl.2014.04.068

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

The discovery and optimization of a series of tetrahydropyridopyrimidine based extracellular signal-regulated kinase (Erks) inhibitors discovered via HTS and structure based drug design is reported. The compounds demonstrate potent and selective inhibition of Erk2 and knockdown of phospho-RSK levels in HepG2 cells and tumor xenografts. (C) 2014 Elsevier Ltd. All rights reserved.

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收藏

页码：2635 / 2639

页数：5

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