Diazinones as P2 replacements for pyrazole-based cathepsin S inhibitors

…, JP Edwards, D Gebauer, Y Gu, L Karlsson…

文献索引：Ameriks, Michael K.; Bembenek, Scott D.; Burdett, Matthew T.; Choong, Ingrid C.; Edwards, James P.; Gebauer, Damara; Gu, Yin; Karlsson, Lars; Purkey, Hans E.; Staker, Bart L.; Sun, Siquan; Thurmond, Robin L.; Zhu, Jian Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 14 p. 4060 - 4064

全文：HTML全文

被引用次数: 8

摘要

A pyridazin-4-one fragment 4 (hCatS IC50= 170μM) discovered through Tethering was modeled into cathepsin S and predicted to overlap in S2 with the tetrahydropyridinepyrazole core of a previously disclosed series of CatS inhibitors. This fragment served as a template to design pyridazin-3-one 12 (hCatS IC50= 430nM), which also incorporates P3 and P5 binding elements. A crystal structure of 12 bound to Cys25Ser CatS led to the synthesis of ...