Synthesis and evaluation of novel pyrimidine-based dual EGFR/Her-2 inhibitors

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1601-6. doi: 10.1016/j.bmcl.2011.01.119. Epub 2011 Feb 2.

Abstract

A structure-activity relationship study of 4-anilinopyrimidines for dual EGFR/Her-2 inhibitor has resulted in the identification of 4-anilino-5-alkenyl or 5-alkynyl-6-methylpyrimidine derivatives that have exhibited effective inhibitory activity against both enzymes. The presence of 5-alkenyl or 5-alkynyl moiety bearing terminal hydrophilic group played important role for inhibition of these enzymes. Selected compounds in the series demonstrated some activity against Her-2 dependent cell line (BT474).

MeSH terms

  • Crystallography, X-Ray
  • Drug Evaluation, Preclinical
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / chemistry
  • Humans
  • Models, Molecular
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacology*
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Pyrimidines
  • ERBB2 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • pyrimidine