Discovery and SAR exploration of a novel series of imidazo [4, 5-b] pyrazin-2-ones as potent and selective mTOR kinase inhibitors

DS Mortensen, SM Perrin-Ninkovic, R Harris…

文献索引：Mortensen, Deborah S.; Perrin-Ninkovic, Sophie M.; Harris, Roy; Lee, Branden G.S.; Shevlin, Graziella; Hickman, Matt; Khambatta, Gody; Bisonette, Rene R.; Fultz, Kimberly E.; Sankar, Sabita Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 22 p. 6793 - 6799

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被引用次数: 16

摘要

We report here the discovery of a novel series of selective mTOR kinase inhibitors. A series of imidazo [4, 5-b] pyrazin-2-ones, represented by screening hit 1, was developed into lead compounds with excellent mTOR potency and exquisite kinase selectivity. Potent compounds from this series show> 1000-fold selectivity over the related PI3Kα lipid kinase. Further, compounds such as 2 achieve mTOR pathway inhibition, blocking both mTORC1 ...