Identification of highly potent and selective PI3Kδ inhibitors

Bioorg Med Chem Lett. 2017 Jul 1;27(13):2849-2853. doi: 10.1016/j.bmcl.2017.01.077. Epub 2017 Feb 7.

Abstract

Selective PI3Kδ inhibitors have recently been hypothesized to be appropriate immunosuppressive agents for the treatment of immunological disorders such as rheumatoid arthritis. However, few reports have highlighted molecules that are highly selective for PI3Kδ over the other PI3K isoforms. In this letter, isoform and kinome selective PI3Kδ inhibitors are presented. The Structural Activity Relationship leading to such molecules is outlined.

Keywords: Autoimmune diseases; PI3Kδ; Phosphoinositide 3-kinases; Pyrrolotriazine; Rheumatoid arthritis.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors