Neutral 5-substituted 4-anilinoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase

Bioorg Med Chem Lett. 2007 Nov 15;17(22):6326-9. doi: 10.1016/j.bmcl.2007.08.073. Epub 2007 Sep 2.

Abstract

Neutral 5-substituted 4-anilinoquinazolines addressed high in vivo clearance and phospholipidosis associated with previous basic compounds. A representative compound 8a inhibited tumor growth in a mouse xenograft model when co-administered with the cytochrome P450 inhibitor 1-aminobenzotriazole (ABT), and data are consistent with pharmacology primarily reflecting inhibition of erbB2 receptor tyrosine kinase.

MeSH terms

  • Administration, Oral
  • Aniline Compounds / chemistry
  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols
  • Cell Proliferation / drug effects
  • Dogs
  • Drug Synergism
  • Mice
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Quinazolines / chemistry*
  • Quinazolines / pharmacokinetics
  • Quinazolines / pharmacology*
  • Rats
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Triazoles / pharmacology
  • Xenograft Model Antitumor Assays

Substances

  • Aniline Compounds
  • Antineoplastic Agents
  • Quinazolines
  • Triazoles
  • 1-aminobenzotriazole
  • Receptor, ErbB-2
  • aniline