噻吩-3-甲酰胺衍生物作为 c-Jun N-端激酶双重抑制剂的设计、合成及构效关系研究。
Design, synthesis, and structure-activity relationship studies of thiophene-3-carboxamide derivatives as dual inhibitors of the c-Jun N-terminal kinase.
机构信息
Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
出版信息
Bioorg Med Chem. 2011 Apr 15;19(8):2582-8. doi: 10.1016/j.bmc.2011.03.017. Epub 2011 Mar 12.
Abstract
We report comprehensive structure-activity relationship studies on a novel series of c-Jun N-terminal kinase (JNK) inhibitors. Intriguingly, the compounds have a dual inhibitory activity by functioning as both ATP and JIP mimetics, possibly by binding to both the ATP binding site and to the docking site of the kinase. Several of such novel compounds display potent JNK inhibitory profiles both in vitro and in cell.
摘要
我们报告了一系列新型 c-Jun N-末端激酶（JNK）抑制剂的全面结构-活性关系研究。有趣的是，这些化合物具有双重抑制活性，既能作为 ATP 又能作为 JIP 模拟物发挥作用，可能通过与 ATP 结合位点和激酶的对接位点结合。其中一些新型化合物在体外和细胞内均表现出很强的 JNK 抑制特性。
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