De Surya K, Stebbins John L, Chen Li-Hsing, Riel-Mehan Megan, Machleidt Thomas, Dahl Russell, Yuan Hongbin, Emdadi Aras, Barile Elisa, Chen Vida, Murphy Ria, Pellecchia Maurizio
Infectious and Inflammatory Disease Center and Cancer Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA.
J Med Chem. 2009 Apr 9;52(7):1943-52. doi: 10.1021/jm801503n.
We report comprehensive structure-activity relationship studies on a novel series of c-Jun N-terminal kinase (JNK) inhibitors. The compounds are substrate competitive inhibitors that bind to the docking site of the kinase. The reported medicinal chemistry and structure-based optimizations studies resulted in the discovery of selective and potent thiadiazole JNK inhibitors that display promising in vivo activity in mouse models of insulin insensitivity.
我们报告了对一系列新型c-Jun氨基末端激酶(JNK)抑制剂的全面构效关系研究。这些化合物是与激酶对接位点结合的底物竞争性抑制剂。所报道的药物化学和基于结构的优化研究导致发现了选择性且强效的噻二唑JNK抑制剂,它们在胰岛素不敏感小鼠模型中显示出有前景的体内活性。