1021916-24-4Relevant articles and documents
Discovery and SAR exploration of a novel series of imidazo[4,5-b]pyrazin-2- ones as potent and selective mTOR kinase inhibitors
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
, p. 6793 - 6799 (2012/01/03)
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 and mTORC2 signaling, in PC3 cancer cells as measured by inhibition of pS6 and pAkt (S473).
