Inhibitors of epidermal growth factor receptor tyrosine kinase: optimisation of potency and in vivo pharmacokinetics

Bioorg Med Chem Lett. 2006 Sep 15;16(18):4908-12. doi: 10.1016/j.bmcl.2006.06.054. Epub 2006 Jun 27.

Abstract

The structure-activity and structure-property relationships of anilinoquinazoline inhibitors of EGFR were investigated. Strategies to lower volume of distribution and shorten half-life through structure and pKa modulation are discussed.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Chemical Phenomena
  • Chemistry, Physical
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Fluorine / chemistry
  • Gefitinib
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Molecular Structure
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacokinetics*
  • Protein Kinase Inhibitors / pharmacology
  • Quinazolines / chemistry
  • Rats
  • Structure-Activity Relationship
  • Thiazoles / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Thiazoles
  • Fluorine
  • 2-anilino-5-thiazolinone
  • ErbB Receptors
  • Gefitinib