Design, synthesis and biological evaluation of thienopyridinones as Chk1 inhibitors.
Design, synthesis and biological evaluation of thienopyridinones as Chk1 inhibitors.
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DOI：
10.1016/j.bmc.2014.06.044
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发表时间：
2014-09
影响因子：
3.5
通讯作者：
Pinrao Song;Peng Peng-Peng;Mengmeng Han;Xianchao Cao;Xiaodong Ma;Tao Liu;Yubo Zhou;Yong-cun Hu
中科院分区：
文献类型：
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作者：
Pinrao Song;Peng Peng-Peng;Mengmeng Han;Xianchao Cao;Xiaodong Ma;Tao Liu;Yubo Zhou;Yong-cun Hu
设计并合成了一系列硫代吡啶酮类化合物作为检查点蛋白1(Chk1)的抑制剂。大多数化合物具有中等到良好的Chk1抑制活性。其中，具有良好的Chk1抑制活性的8q、8t和8w3个化合物(IC50值分别为4.05、6.23和2.33nM)与细胞实验中的DNA损伤剂马法兰显示出很强的协同作用。进一步的激酶谱分析表明，化合物8T对CDK2/CyclinA、Aurora A和PKC具有高度的选择性。
A series of thienopyridinone derivatives was designed and synthesized as inhibitors of checkpoint kinase 1 (Chk1). Most of them exhibited moderate to good Chk1 inhibitory activities. Among them, compounds8q,8t, and8wwith excellent Chk1 inhibitory activities (IC50values of 4.05, 6.23, and 2.33 nM, respectively) displayed strong synergistic effects with melphalan, a DNA-damaging agent in the cell-based assay. Further kinase profiling indicated that compound8twas highly selective against CDK2/cyclinA, Aurora A, and PKC.