Discovery of new 4-alkoxyquinazoline-based derivatives as potent VEGFR2 inhibitors

Chem Biol Drug Des. 2015 Nov;86(5):1323-9. doi: 10.1111/cbdd.12596. Epub 2015 Jun 23.

Abstract

VEGFR2 has been proved to play a major role in the regulation of tumor angiogenesis. Twenty-one 4-alkoxyquinazoline-based derivatives have been designed and synthesized as vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors, and their biological activities were evaluated. Among these compounds, compound 3h exhibited the most potent inhibitory activities against VEGFR2 tyrosine kinase and cell proliferation, with the IC50 values of 2.89 nm (for VEGFR2) and 0.25 μm (for MCF-7), which were comparable with the control compound. Docking simulation was performed to position compound 3h into the 4ASE active site, and the result showed that compound 3h could bind well at the 4ASE active site.

Keywords: 4-alkoxyquinazoline-based derivatives; VEGFR2 inhibitors; molecular docking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemistry*
  • Angiogenesis Inhibitors / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Design
  • Humans
  • Molecular Docking Simulation
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Quinazolines / chemistry*
  • Quinazolines / pharmacology*
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Angiogenesis Inhibitors
  • Protein Kinase Inhibitors
  • Quinazolines
  • Vascular Endothelial Growth Factor Receptor-2