1021915-91-2Relevant academic research and scientific papers
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).
HETEROARYL COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
-
Page/Page column 118, (2008/12/05)
Provided herein are Heteroaryl Compounds having the following structure: (I) wherein R1, R2, L, X, Y, Z, Q, A and B are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heteroaryl Compound to a patient in need thereof.
