Synthesis, structural analysis, and SAR studies of triazine derivatives as potent, selective Tie-2 inhibitors

Bioorg Med Chem Lett. 2007 May 15;17(10):2886-9. doi: 10.1016/j.bmcl.2007.02.067. Epub 2007 Feb 25.


A novel class of selective Tie-2 inhibitors was derived from a multi-kinase inhibitor 1. By reversing the amide connectivity and incorporating aminotriazine or aminopyridine hinge-binding moieties, excellent Tie-2 potency and KDR selectivity could be achieved with 3-substituted terminal aryl rings. X-ray co-crystal structure analysis aided inhibitor design. This series was evaluated on the basis of potency, selectivity, and rat pharmacokinetic parameters.

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Drug Design
  • Male
  • Models, Molecular
  • Molecular Structure
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, TIE-2 / antagonists & inhibitors*
  • Receptor, TIE-2 / chemistry
  • Structure-Activity Relationship
  • Triazines / chemistry
  • Triazines / pharmacology*


  • Triazines
  • Receptor, TIE-2