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

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.

• Authors: Peter Ballard, Bernard C Barlaam, Robert H Bradbury, Allan Dishington, Laurent F A Hennequin, D Mark Hickinson, Ian M Hollingsworth, Jason G Kettle, Teresa Klinowska, Donald J Ogilvie, Stuart E Pearson, James S Scott, Abid Suleman, Robin Whittaker, Emma J Williams, Robin Wood, Lindsay Wright
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 17 Issue 22 Pg. 6326-9 (Nov 15 2007) ISSN: 0960-894X [Print] England
• PMID: 17869514 (Publication Type: Journal Article)

Chemical References

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

Topics

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