740842-73-3Relevant articles and documents
Process Development and Scale-Up of a Benzoxazepine-Containing Kinase Inhibitor
Naganathan, Sriram,Andersen, Denise L.,Andersen, Neil G.,Lau, Stephen,Lohse, Anders,Sorensen, Mads Detlef
, p. 721 - 734 (2015/07/27)
The benzoxazepine core is present in several kinase inhibitors, including the mTOR inhibitor 1. The process development for a scalable synthesis of 7-bromobenzoxazepine and the telescoped synthesis of 1 are reported. Compound 1 consists of three chemicall
Discovery of a novel class of highly potent, selective, ATP-competitive, and orally bioavailable inhibitors of the mammalian target of rapamycin (mTOR)
Takeuchi, Craig S.,Kim, Byung Gyu,Blazey, Charles M.,Ma, Sunghoon,Johnson, Henry W. B.,Anand, Neel K.,Arcalas, Arlyn,Baik, Tae Gon,Buhr, Chris A.,Cannoy, Jonah,Epshteyn, Sergey,Joshi, Anagha,Lara, Katherine,Lee, Matthew S.,Wang, Longcheng,Leahy, James W.,Nuss, John M.,Aay, Naing,Aoyama, Ron,Foster, Paul,Lee, Jae,Lehoux, Isabelle,Munagala, Narsimha,Plonowski, Arthur,Rajan, Sharmila,Woolfrey, John,Yamaguchi, Kyoko,Lamb, Peter,Miller, Nicole
, p. 2218 - 2234 (2013/05/22)
A series of novel, highly potent, selective, and ATP-competitive mammalian target of rapamycin (mTOR) inhibitors based on a benzoxazepine scaffold have been identified. Lead optimization resulted in the discovery of inhibitors with low nanomolar activity and greater than 1000-fold selectivity over the closely related PI3K kinases. Compound 28 (XL388) inhibited cellular phosphorylation of mTOR complex 1 (p-p70S6K, pS6, and p-4E-BP1) and mTOR complex 2 (pAKT (S473)) substrates. Furthermore, this compound displayed good pharmacokinetics and oral exposure in multiple species with moderate bioavailability. Oral administration of compound 28 to athymic nude mice implanted with human tumor xenografts afforded significant and dose-dependent antitumor activity.
BENZOXAZEPINES AS INHIBITORS OF PI3K/MTOR AND METHODS OF THEIR USE AND MANUFACTURE
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Page/Page column 70, (2012/06/16)
The invention is directed to inhibitors of PI3K and mTOR and pharmaceutically acceptable salts or solvates thereof, as well as methods of using them, wherein the inhibitors are of structural Formula I and pharmaceutically acceptable salts thereof, wherein
