Synthesis and biological evaluation of quinoxaline derivatives as specific c-Met kinase inhibitors

Bioorg Med Chem Lett. 2020 Jul 1;30(13):127189. doi: 10.1016/j.bmcl.2020.127189. Epub 2020 Apr 16.

Abstract

A series of novel quinoxaline derivatives were synthesized and evaluated for their inhibitory activity against c-Met kinase enzyme. Most of the tested compounds exhibited potent inhibitory activity. All the synthesized quinoxaline compounds were further examined against c-Met overexpressed human gastric cancer cell line (MKN-45), which showed good inhibitory activity. Among the synthesized compounds, compound 4 exhibited better tumor growth inhibition in the animal model study; we also confirmed its acceptable drug property and highly selective target activity.

Keywords: Quinoxaline; Synthesis; c-Met inhibitors; c-Met kinase.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Humans
  • Mice
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Quinoxalines / chemical synthesis
  • Quinoxalines / pharmacology*
  • Quinoxalines / therapeutic use
  • Rats
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinoxalines
  • Proto-Oncogene Proteins c-met