Discovery of novel PI3Kγ/δ inhibitors as potential agents for inflammation

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4546-9. doi: 10.1016/j.bmcl.2012.05.121. Epub 2012 Jun 9.


Dual PI3Kγ/δ inhibitors have recently been shown to be suitable targets for inflammatory and respiratory diseases. In a recent study we described the discovery of selective PI3Kγ inhibitors based on a triazolopyridine scaffold. Herein, we describe the elaboration of this structural class into dual PI3Kγ/δ inhibitors with excellent selectivity over the other PI3K isoforms and the general kinome. Structural optimization led to the identification of two derivatives which showed significant efficacy in an acute model of lung inflammation.

MeSH terms

  • Drug Discovery
  • Inflammation / drug therapy
  • Models, Molecular
  • Molecular Structure
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Structure-Activity Relationship


  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors