Pyridylmethylthio derivatives as VEGF inhibitors. Part 1

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7234-8. doi: 10.1016/j.bmcl.2010.10.096. Epub 2010 Oct 26.

Abstract

Optimization from compound 4a, having intramolecular S-O nonbonded interaction, led to discover compounds 4m and 4n. They were highly active in vitro (VEGF induced HUVEC proliferation assay) and showed efficacies in three disease models in vivo (cancer, RA, AMD).

MeSH terms

  • Anilides / chemical synthesis
  • Anilides / chemistry*
  • Anilides / therapeutic use
  • Animals
  • Arthritis, Experimental / drug therapy
  • Cell Line
  • Choroidal Neovascularization / drug therapy
  • Disease Models, Animal
  • Endothelial Cells / cytology
  • Humans
  • Mice
  • Neoplasms / drug therapy
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / therapeutic use
  • Rats
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Anilides
  • Pyridines
  • Vascular Endothelial Growth Factor A
  • pyridine