Inhibitors of the tyrosine kinase EphB4. Part 2: structure-based discovery and optimisation of 3,5-bis substituted anilinopyrimidines

Bioorg Med Chem Lett. 2008 Nov 1;18(21):5717-21. doi: 10.1016/j.bmcl.2008.09.087. Epub 2008 Sep 27.


Crystallographic studies of a range of 3-substituted anilinopyrimidine inhibitors of EphB4 have highlighted two alternative C-2 aniline conformations and this discovery has been exploited in the design of a highly potent series of 3,5-disubstituted anilinopyrimidines. The observed range of cellular activities has been rationalised on the basis of physicochemical and structural characteristics.

MeSH terms

  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Receptor, EphB4 / antagonists & inhibitors*


  • Protein Kinase Inhibitors
  • Pyrimidines
  • Receptor, EphB4