Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: Synthesis and SAR study as tyrosine kinase c-Met inhibitors
Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: Synthesis and SAR study as tyrosine kinase c-Met inhibitors
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DOI：
10.1016/j.bmcl.2012.08.075
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发表时间：
2012-10-15
影响因子：
2.7
通讯作者：
Zhang, Ao
中科院分区：
文献类型：
--
作者：
Wu, Kui;Ai, Jing;Zhang, Ao
通过用喹喔啉和吡啶并[2,3-d]嘧啶框架取代我们早期的先导2（zgw-atinib）的喹啉支架，设计了两个系列的新类似物。在喹喔啉系列中观察到中等的 c-Met 抑制活性。在吡啶并[2,3-d]嘧啶系列中，具有O-连接的化合物13a-c是无活性的，而N-连接的类似物15a-c保留了c-Met抑制效力。在 3-硝基苄基类似物 15b 中观察到最高活性，其 IC50 值为 6.5 nM。基于该化合物的进一步结构修饰正在进行中。 (c) 2012 Elsevier Ltd. 保留所有权利。
Two series of new analogues were designed by replacing the quinoline scaffold of our earlier lead 2 (zgw-atinib) 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. (c) 2012 Elsevier Ltd. All rights reserved.