Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: Synthesis and SAR study as tyrosine kinase c-Met inhibitors

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• 作者：Kui Wu ; Jing Ai ; Qiufeng Liu ; TianTian Chen ; Ailing Zhao ; Xia Peng ; Yuanxiang Wang ; Yinchun Ji ; Qizheng Yao ; Yechun Xu ; Meiyu Geng ; Ao Zhang
• 关键词：c-Met kinase ; 3 ; 5-Diamino-7-trifluoroquinoline ; hERG ; Antitumor activity ; Structure&ndash ; activity relationship (SAR)
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：15 October, 2012
• 年：2012
• 卷：22
• 期：20
• 页码：6368-6372
• 全文大小：1266 K

文摘

Two series of new analogues were designed by replacing the quinoline scaffold of our earlier lead 2 (zgwatinib) with quinoxaline and pyrido[2,3-d]pyrimidine frameworks. Moderate c-Met inhibitory activity was observed in the quinoxaline series. Among the pyrido[2,3-d]pyrimidine series, compounds 13a-c possessing an O-linkage were inactive, whilst the N-linked analogues 15a-c retained c-Met inhibitory potency. Highest activity was observed in the 3-nitrobenzyl analog 15b that showed an IC₅₀ value of 6.5 nM. Further structural modifications based on this compound were undergoing.