1105709-92-9Relevant academic research and scientific papers
Azole-based inhibitors of AKT/PKB for the treatment of cancer
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
scheme or table, p. 1559 - 1564 (2010/06/16)
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 bound to AKT1 and to the counter-screening target PKA. One compound was shown to have acceptable pharmacokinetic properties and to be a potent inhibitor of AKT signaling and of in vivo xenograft tumor growth in a preclinical model of glioblastoma.
HETEROCYCLIC MODULATORS OF PKB
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Page/Page column 91; 93-94, (2009/03/07)
The invention relates to heterocyclic compounds of Formula I and compositions thereof useful for treating diseases mediated by protein kinase B (PKB) where the variables have the definitions provided herein Formula (I). The invention also relates to the therapeutic use of such compounds and compositions thereof in treating disease states associated with abnormal cell growth, cancer, inflammation, and metabolic disorders.
