Synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK inhibitors with anti-angiogenic activity

Bioorg Med Chem Lett. 2013 Aug 15;23(16):4552-6. doi: 10.1016/j.bmcl.2013.06.038. Epub 2013 Jun 24.


We report herein the synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK (focal adhesion kinase) inhibitors and the evaluation of their anti-angiogenic activity on HUVEC cells. Generally, the effects of these compounds on endothelial cells could be correlated with their kinase inhibitory activity. The most efficient compounds displayed inhibition of viability against HUVEC cells in the micromolar range, as observed with TAE-226, which was designed by Novartis Pharma AG. X-ray crystallographic analysis of the co-crystal structure for compound 34 revealed that the mode of interaction with the FAK kinase domain is highly similar to that observed in the complex of TAE-226.

Keywords: Anti-angiogenic activity; Diarylamino-1,3,5-triazines; FAK inhibitors; Synthesis; X-ray structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Endothelial Cells / drug effects
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Molecular Structure
  • Morpholines / chemistry
  • Morpholines / pharmacology
  • Triazines / chemical synthesis*
  • Triazines / chemistry
  • Triazines / pharmacology


  • Angiogenesis Inhibitors
  • Enzyme Inhibitors
  • Morpholines
  • TAE226
  • Triazines
  • Focal Adhesion Protein-Tyrosine Kinases