Synthesis and SAR study of potent and selective PI3Kδ inhibitors

Bioorg Med Chem Lett. 2015 Mar 1;25(5):1104-9. doi: 10.1016/j.bmcl.2015.01.001. Epub 2015 Jan 17.

Abstract

2,3,4-Substituted quinolines such as (10a) were found to be potent inhibitors of PI3Kδ in both biochemical and cellular assays with good selectivity over three other class I PI3K isoforms. Some of those analogs showed favorable pharmacokinetic properties.

Keywords: Autoimmune disorders; Inflammation; PI3Kδ; Reversed quinolines.

MeSH terms

  • Animals
  • Class I Phosphatidylinositol 3-Kinases / antagonists & inhibitors*
  • Class I Phosphatidylinositol 3-Kinases / metabolism
  • Humans
  • Male
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / metabolism
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / pharmacokinetics
  • Quinolines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • Protein Isoforms
  • Protein Kinase Inhibitors
  • Quinolines
  • Class I Phosphatidylinositol 3-Kinases