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 ...
[Lin, Shuqun; Wrobleski, Stephen T.; Hynes Jr., John; Pitt, Sidney; Zhang, Rosemary; Fan, Yi; Doweyko, Arthur M.; Kish, Kevin F.; Sack, John S.; Malley, Mary F.; Kiefer, Susan E.; Newitt, John A.; McKinnon, Murray; Trzaskos, James; Barrish, Joel C.; Dodd, John H.; Schieven, Gary L.; Leftheris, Katerina Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 19 p. 5864 - 5868]
