Title of article :
Identification of a novel 3,5-disubstituted pyridine as a potent, selective, and orally active inhibitor of Akt1 kinase
Author/Authors :
Sheela A. Thomas، نويسنده , , Tongmei Li، نويسنده , , Keith W. Woods، نويسنده , , Xiaohong Song، نويسنده , , Garrick Packard، نويسنده , , John P. Fischer، نويسنده , , Robert B. Diebold، نويسنده , , Xuesong Liu، نويسنده , , Yan Shi، نويسنده , , Vered Klinghofer، نويسنده , , Eric F. Johnson، نويسنده , , Jennifer J. Bouska، نويسنده , , Amanda Olson، نويسنده , , Ran Guan، نويسنده , , Shayna R. Magnone، نويسنده , , Kennan Marsh، نويسنده , , Yan Luo، نويسنده , , Saul H. Rosenberg، نويسنده , , Vincent L. Giranda، نويسنده , , Qun Li، نويسنده ,
Abstract :
Based on lead compounds 2 and 3 a series of 3,5-disubstituted pyridines have been designed and evaluated for inhibition of AKT/PKB. Modifications at the 3 position of the pyridine ring led to a number of potent compounds with improved physical properties, resulting in the identification of 11g as a promising, orally active Akt inhibitor. The synthesis, structure–activity relationship studies, and pharmacokinetic data are presented in this paper.
Keywords :
3 , 5-Disubstituted pyridines , AKT inhibitors , Akt/PKB
