Synthesis and evaluation of aniline headgroups for alkynyl thienopyrimidine dual EGFR/ErbB-2 kinase inhibitors

Bioorg Med Chem Lett. 2009 Mar 1;19(5):1332-6. doi: 10.1016/j.bmcl.2009.01.080. Epub 2009 Feb 7.

Abstract

Aniline 'headgroups' were synthesized and incorporated into an alkynyl thienopyrimidine series of EGFR and ErbB-2 inhibitors. Potent inhibition of enzyme activity and cellular proliferation was observed. In certain instances, protein binding was reduced and oral exposure was found to be somewhat improved relative to compounds containing the reference aniline.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Aniline Compounds / administration & dosage
  • Aniline Compounds / chemical synthesis*
  • Aniline Compounds / pharmacology
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Evaluation, Preclinical / methods
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Growth Inhibitors / administration & dosage
  • Growth Inhibitors / chemical synthesis
  • Growth Inhibitors / pharmacology
  • Humans
  • Mice
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / pharmacology
  • Pyrimidines / administration & dosage
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacology
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / metabolism

Substances

  • Aniline Compounds
  • Growth Inhibitors
  • Protein Kinase Inhibitors
  • Pyrimidines
  • thienopyrimidine
  • EGFR protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • aniline