Inhibiting NF-κB-inducing kinase (NIK): Discovery, structure-based design, synthesis, structure–activity relationship, and co-crystal structures

…, F Lee, J Eksterowicz, P Faulder, B Waszkowycz…

文献索引：Li, Kexue; McGee, Lawrence R.; Fisher, Ben; Sudom, Athena; Liu, Jinsong; Rubenstein, Steven M.; Anwer, Mohmed K.; Cushing, Timothy D.; Shin, Youngsook; Ayres, Merrill; Lee, Fei; Eksterowicz, John; Faulder, Paul; Waszkowycz, Bohdan; Plotnikova, Olga; Farrelly, Ellyn; Xiao, Shou-Hua; Chen, Guoqing; Wang, Zhulun Bioorganic and Medicinal Chemistry Letters, 2013 , vol. 23, # 5 p. 1238 - 1244

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被引用次数: 17

摘要

The discovery, structure-based design, synthesis, and optimization of NIK inhibitors are described. Our work began with an HTS hit, imidazopyridinyl pyrimidinamine 1. We utilized homology modeling and conformational analysis to optimize the indole scaffold leading to the discovery of novel and potent conformationally constrained inhibitors such as compounds 25 and 28. Compounds 25 and 31 were co-crystallized with NIK kinase ...