Title of article :
Optimization of 2,3,5-trisubstituted pyridine derivatives as potent allosteric Akt1 and Akt2 inhibitors
Author/Authors :
John C. Hartnett، نويسنده , , Stanley F. Barnett، نويسنده , , Mark T. Bilodeau، نويسنده , , Deborah Defeo-Jones، نويسنده , , George D. Hartman، نويسنده , , Hans E. Huber، نويسنده , , Raymond E. Jones، نويسنده , , Astrid M. Kral، نويسنده , , Ronald G. Robinson، نويسنده , , Zhicai Wu، نويسنده ,
Abstract :
This letter shows inhibitor SAR on a pyridine series of allosteric Akt inhibitors to optimize enzymatic and cellular potency. We have optimized 2,3,5-trisubstituted pyridines to give potent Akt1 and Akt2 inhibitors in both enzyme and cell based assays. In addition, we will also highlight the pharmacokinetic profile of an optimized inhibitor that has low clearance and long half-life in dogs.
Keywords :
enzymatic , AKT2 , Inhibitors , cellular , AKT1
