Structure-based optimization of aminopyridines as PKCθ inhibitors

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4645-9. doi: 10.1016/j.bmcl.2012.05.114. Epub 2012 Jun 6.

Abstract

The identification of a novel series of PKCθ inhibitors and subsequent optimization using docking based on a crystal structure of PKCθ is described. SAR was rapidly generated around an amino pyridine-ketone hit; (6-aminopyridin-2-yl)(2-aminopyridin-3-yl)methanone 2 leading to compound 21 which significantly inhibits production of IL-2 in a mouse SEB-IL2 model.

MeSH terms

  • Aminopyridines / chemistry*
  • Aminopyridines / pharmacology
  • Animals
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Aminopyridines
  • Protein Kinase Inhibitors
  • Protein Kinase C