Azole-based inhibitors of AKT/PKB for the treatment of cancer

Q Zeng, JG Allen, MP Bourbeau, X Wang, G Yao…

Index: Zeng, Qingping; Allen, John G.; Bourbeau, Matthew P.; Wang, Xianghong; Yao, Guomin; Tadesse, Seifu; Rider, James T.; Yuan, Chester C.; Hong, Fang-Tsao; Lee, Matthew R.; Zhang, Shiwen; Lofgren, Julie A.; Freeman, Daniel J.; Yang, Suijin; Li, Chun; Tominey, Elizabeth; Huang, Xin; Hoffman, Douglas; Yamane, Harvey K.; Fotsch, Christopher; Dominguez, Celia; Hungate, Randall; Zhang, Xiaoling Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 5 p. 1559 - 1564

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Citation Number: 11

Abstract

Through a combination of screening and structure-based rational design, we have discovered a series of N1-(5-(heterocyclyl)-thiazol-2-yl)-3-(4-trifluoromethylphenyl)-1, 2- propanediamines that were developed into potent ATP competitive inhibitors of AKT. Studies of linker strand-binding adenine isosteres identified SAR trends in potency and selectivity that were consistent with binding interactions observed in structures of the inhibitors ...

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