2,4-disubstituted pyrimidines: a novel class of KDR kinase inhibitors

Bioorg Med Chem Lett. 2003 May 19;13(10):1673-7. doi: 10.1016/s0960-894x(03)00244-0.

Abstract

2,4-Disubstituted pyrimidines were synthesized as a novel class of KDR kinase inhibitors. Evaluation of the SAR of the screening lead compound 1 (KDR IC(50)=105 nM, Cell IC(50)=8% inhibition at 500 nM) led to the potent 3,5-dimethylaniline derivative 2d (KDR IC(50)=6 nM, cell IC(50)=19 nM).

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / pharmacology
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Cells, Cultured
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Pyrimidines / chemical synthesis
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Pyrimidines
  • Vascular Endothelial Growth Factor Receptor-2