Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
Bioorg Med Chem Lett. 2012 Oct 15;22(20):6368-72. doi: 10.1016/j.bmcl.2012.08.075. Epub 2012 Aug 27.
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 IC(50) value of 6.5 nM. Further structural modifications based on this compound were undergoing.
我们设计了两个新的类似物系列，通过用喹喔啉和吡啶并[2,3-d]嘧啶骨架替代我们早期先导化合物 2（zgw-atinib）中的喹啉支架。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 没有活性，而 N 连接的类似物 15a-c 保留了 c-Met 抑制活性。在具有 3-硝基苄基的类似物 15b 中观察到最高的活性，其 IC50 值为 6.5 nM。正在对基于该化合物的进一步结构修饰进行研究。
