A new series of neutral 5-substituted 4-anilinoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase

Bioorg Med Chem Lett. 2008 Jan 15;18(2):674-8. doi: 10.1016/j.bmcl.2007.11.052. Epub 2007 Nov 21.

Abstract

Starting from initial lead 1 containing a basic 5-substituent, optimisation of the glycolamide-derived neutral 5-substituent led to potent inhibitors of erbB2 with good pharmacokinetics. Representative compounds 19 and 21 inhibited phosphorylation of erbB2 in a mouse BT474C xenograft model after oral administration.

MeSH terms

  • Administration, Oral
  • Animals
  • Cell Line
  • Magnetic Resonance Spectroscopy
  • Mice
  • Neoplasm Transplantation
  • Phosphorylation
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Quinazolines / administration & dosage
  • Quinazolines / chemistry
  • Quinazolines / pharmacokinetics
  • Quinazolines / pharmacology*
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Protein Kinase Inhibitors
  • Quinazolines
  • Receptor, ErbB-2