Discovery of potent and selective inhibitors of the mammalian target of rapamycin (mTOR) kinase

…, DJ Malwitz, L Toral-Barza, JC Verheijen…

Index: Nowak, Pawel; Cole, Derek C.; Brooijmans, Natasja; Bursavich, Matthew G.; Curran, Kevin J.; Ellingboe, John W.; Gibbons, James J.; Hollander, Irwin; Hu, YongBo; Kaplan, Joshua; Malwitz, David J.; Toral-Barza, Lourdes; Verheijen, Jeroen C.; Zask, Arie; Zhang, Wei-Guo; Yu, Ker Journal of Medicinal Chemistry, 2009 , vol. 52, # 22 p. 7081 - 7089

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Citation Number: 42

Abstract

The mammalian target of rapamycin (mTOR) is a central regulator of cell growth, metabolism, and angiogenesis and an emerging target in cancer research. High throughput screening (HTS) of our compound collection led to the identification of 3-(4-morpholin-4-yl-1- piperidin-4-yl-1 H-pyrazolo [3, 4-d] pyrimidin-6-yl) phenol (5a), a modestly potent and nonselective inhibitor of mTOR and phosphoinositide 3-kinase (PI3K). Optimization of ...