Discovery and optimization of a series of 3-(3-Phenyl-3 H-imidazo [4, 5-b] pyridin-2-yl) pyridin-2-amines: orally bioavailable, selective, and potent ATP-independent …

…, S Cornell-Kennon, S Eathiraj, DS France…

文献索引：Ashwell, Mark A.; Lapierre, Jean-Marc; Brassard, Christopher; Bresciano, Karen; Bull, Cathy; Cornell-Kennon, Susan; Eathiraj, Sudharshan; France, Dennis S.; Hall, Terence; Hill, Jason; Kelleher, Eoin; Khanapurkar, Sampada; Kizer, Darin; Koerner, Steffi; Link, Jeff; Liu, Yanbin; Makhija, Sapna; Moussa, Magdi; Namdev, Nivedita; Nguyen, Khanh; Nicewonger, Robert; Palma, Rocio; Szwaya, Jeff; Tandon, Manish; Uppalapati, Uma; Vensel, David; Volak, Laurie P.; Volckova, Erika; Westlund, Neil; Wu, Hui; Yang, Rui-Yang; Chan, Thomas C. K. Journal of Medicinal Chemistry, 2012 , vol. 55, # 11 p. 5291 - 5310

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被引用次数: 27

摘要

This paper describes the implementation of a biochemical and biophysical screening strategy to identify and optimize small molecule Akt1 inhibitors that act through a mechanism distinct from that observed for kinase domain ATP-competitive inhibitors. With the aid of an unphosphorylated Akt1 cocrystal structure of 12j solved at 2.25 Å, it was possible to confirm that as a consequence of binding these novel inhibitors, the ATP binding cleft contained a ...