Synthesis and biological evaluation of sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474

Bioorg Med Chem. 2017 Oct 15;25(20):5859-5874. doi: 10.1016/j.bmc.2017.09.025. Epub 2017 Sep 20.


Replacement of one of the morpholine groups of the phosphatidylinositol 3-kinase (PI3K) inhibitor ZSTK474 (1) with sulfonamide containing substituents produced a new class of active and potent PI3Kα inhibitors. Solubility issues prevented all but the 6-amino derivative 17 from being evaluated in vivo, but the clear activity of this compound demonstrated that this class of PI3K inhibitor shows great promise.

Keywords: PI3K; Phosphatidylinositol 3-kinase; ZSTK474; p110α.

MeSH terms

  • Cell Line, Tumor
  • Enzyme Activation / drug effects
  • Humans
  • Molecular Structure
  • Phosphoinositide-3 Kinase Inhibitors*
  • Solubility
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Triazines / chemistry*
  • Triazines / pharmacology


  • Phosphoinositide-3 Kinase Inhibitors
  • Sulfonamides
  • Triazines
  • ZSTK474