Synthesis of kinase inhibitors containing a pentafluorosulfanyl moiety

Org Biomol Chem. 2017 Oct 18;15(40):8655-8660. doi: 10.1039/c7ob02289a.

Abstract

A series of 3-methylidene-1H-indol-2(3H)-ones substituted with a 5- or 6-pentafluorosulfanyl group has been synthesized by a Knoevenagel condensation reaction of SF5-substituted oxindoles with a range of aldehydes. The resulting products were characterized by X-ray crystallography studies and were tested for biological activity versus a panel of cell lines and protein kinases. Some exhibited single digit nM activity.

MeSH terms

  • Cell Line
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Fluorides / chemical synthesis
  • Fluorides / chemistry
  • Fluorides / pharmacology*
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Oxindoles
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / metabolism*
  • Structure-Activity Relationship
  • Sulfur Compounds / chemical synthesis
  • Sulfur Compounds / chemistry
  • Sulfur Compounds / pharmacology*

Substances

  • Indoles
  • Oxindoles
  • Protein Kinase Inhibitors
  • Sulfur Compounds
  • sulfur pentafluoride cation
  • 2-oxindole
  • Protein Kinases
  • Fluorides