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

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• 作者：James F. Blake^a ; ^{jblake@arraybiopharma.com" class="auth_mail} ; John J. Gaudino^a ; Jason De Meese^a ; Peter Mohr^a ; Mark Chicarelli^a ; Hongqi Tian^a ; Rustam Garrey^a ; Allen Thomas^a ; Christopher S. Siedem^a ; Michael B. Welch^a ; Gabrielle Kolakowski^a ; Robert Kaus^a ; Michael Burkard^a ; Matthew Martinson^a ; Huifen Chen^b ; Brian Dean^b ; Danette A. Dudley^b ; Stephen E. Gould^b ; Patricia Pacheco^b ; Sheerin Shahidi-Latham^b ; Weiru Wang^b ; Kristina West^b ; Jianping Yin^b ; John Moffat^b ; Jacob B. Schwarz^b
• 关键词：Erk2 kinase inhibitors ; Mek resistance ; Structure based drug design
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：15 June 2014
• 年：2014
• 卷：24
• 期：12
• 页码：2635-2639
• 全文大小：1175 K

文摘

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.