Chemoselective synthesis and biological evaluation of arylated 2-(Trifluoromethyl) quinolines as nucleotide pyrophosphatase (NPPs) inhibitors

Eur J Med Chem. 2017 Sep 29:138:816-829. doi: 10.1016/j.ejmech.2017.07.017. Epub 2017 Jul 13.

Abstract

A new approach to arylated 2-trifluoromethylquinolines based on novel regioselective Suzuki-Miyaura coupling reactions has been developed. Moreover, site-selective, chemo-selective amination reactions were performed. The new 2-trifluoromethylquinoline derivatives were tested as potential NPPs inhibitors and evaluated for their potential to inhibit two families of ecto-nucleotidases, i.e. NPPs and nucleoside triphosphate diphosphohydrolases (NTPDases). Several derivatives were active on a nanomolecular concentration. The results were validated based on docking studies to study the active binding site of the molecules.

Keywords: Palladium catalysis; Phosphatase inhibitors; Quinolines; Regioselectivity.

MeSH terms

  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Pyrophosphatases / antagonists & inhibitors*
  • Pyrophosphatases / metabolism
  • Quinolines / chemical synthesis
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Quinolines
  • Pyrophosphatases
  • nucleotide pyrophosphatase