Allosteric inhibitors of Akt1 and Akt2: discovery of [1,2,4]triazolo[3,4-f][1,6]naphthyridines with potent and balanced activity

  • Bioorg Med Chem Lett. 2009 Feb 1;19(3):834-6. doi: 10.1016/j.bmcl.2008.12.017.
Yiwei Li  1 ,  Jun Liang ,  Tony Siu ,  Essa Hu ,  Michael A Rossi ,  Stanley F Barnett ,  Deborah Defeo-Jones ,  Raymond E Jones ,  Ronald G Robinson ,  Karen Leander ,  Hans E Huber ,  Sachin Mittal ,  Nicholas Cosford ,  Peppi Prasit
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., 770 Sumneytown Pike, WP14-2, West Point, PA 19486, USA. [email protected]
PMID: 19097777 DOI: 10.1016/j.bmcl.2008.12.017
Abstract

A series of [1,2,4]triazolo[3,4-f][1,6]naphthyridine allosteric dual inhibitors of Akt1 and 2 have been developed. These compounds have been shown to have potent dual Akt1 and 2 cell potency. The representative compound 13 provided potent inhibitory activity against Akt1 and 2 in vivo in a mouse model.