Discovery and optimization of 2-(4-substituted-pyrrolo [2, 3-b] pyridin-3-yl) methylene-4-hydroxybenzofuran-3 (2H)-ones as potent and selective ATP-competitive …

…, I Hollander, TS Mansour, S Ayral-Kaloustian…

Index: Tsou, Hwei-Ru; MacEwan, Gloria; Birnberg, Gary; Grosu, George; Bursavich, Matthew G.; Bard, Joel; Brooijmans, Natasja; Toral-Barza, Lourdes; Hollander, Irwin; Mansour, Tarek S.; Ayral-Kaloustian, Semiramis; Yu, Ker Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 7 p. 2321 - 2325

Full Text: HTML

Citation Number: 22

Abstract

We discovered 2-(4-substituted-pyrrolo [2, 3-b] pyridin-3-yl) methylene-4-hydroxybenzofuran- 3 (2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR). Since phenolic OH groups pose metabolic liability, one of the two hydroxyl groups was selectively removed. The SAR data showed the structural features necessary for subnanomolar inhibitory activity against mTOR kinase as well as selectivity ...