Design, synthesis and SAR of thienopyridines as potent CHK1 inhibitors

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• 作者：Lianyun Zhao ; Yingxin Zhang ; Chaoyang Dai ; Timothy Guzi ; Derek Wiswell ; Wolfgang Seghezzi ; David Parry ; Thierry Fischmann ; M. Arshad Siddiqui
• 关键词：CHK1 inhibitors ; Thienopyridines ; Antitutor agent ; Kinase inhibitor
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：15 December 2010
• 年：2010
• 卷：20
• 期：24
• 页码：7216-7221
• 全文大小：3468 K

文摘

A novel series of CHK1 inhibitors based on thienopyridine template has been designed and synthesized. These inhibitors maintain critical hydrogen bonding with the hinge and conserved water in the ATP binding site. Several compounds show single digit nanomolar CHK1 activities. Compound 70 shows excellent enzymatic activity of 1 nM.