Identification of a novel 3,5-disubstituted pyridine as a potent, selective, and orally active inhibitor of Akt1 kinase

  • Bioorg Med Chem Lett. 2006 Jul 15;16(14):3740-4. doi: 10.1016/j.bmcl.2006.04.046.
Sheela A Thomas  1 ,  Tongmei Li ,  Keith W Woods ,  Xiaohong Song ,  Garrick Packard ,  John P Fischer ,  Robert B Diebold ,  Xuesong Liu ,  Yan Shi ,  Vered Klinghofer ,  Eric F Johnson ,  Jennifer J Bouska ,  Amanda Olson ,  Ran Guan ,  Shayna R Magnone ,  Kennan Marsh ,  Yan Luo ,  Saul H Rosenberg ,  Vincent L Giranda ,  Qun Li
Affiliations
  • 1. Cancer Research, Department R47S, AP10 Abbott Laboratories, 100 Abbott Park Rd, Abbott Park, IL 60064, USA. [email protected]
PMID: 16678413 DOI: 10.1016/j.bmcl.2006.04.046
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.