Thienopyrimidine-based dual EGFR/ErbB-2 inhibitors.

Abstract

Two new series of potent and selective dual EGFR/ErbB-2 kinase inhibitors derived from novel thienopyrimidine cores have been identified. Isomeric thienopyrimidine cores were evaluated as isosteres for a 4-anilinoquinazoline core and several analogs containing the thieno[3,2-d]pyrimidine core showed anti-proliferative activity with IC(50) values less than 1 microM against human tumor cells in vitro.

• Authors: Tara R Rheault, Thomas R Caferro, Scott H Dickerson, Kelly H Donaldson, Michael D Gaul, Aaron S Goetz, Robert J Mullin, Octerloney B McDonald, Kimberly G Petrov, David W Rusnak, Lisa M Shewchuk, Glenn M Spehar, Anne T Truesdale, Dana E Vanderwall, Edgar R Wood, David E Uehling
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 19 Issue 3 Pg. 817-20 (Feb 01 2009) ISSN: 1464-3405 [Electronic] England
• PMID: 19111461 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• Pyrimidines
• Quinazolines
• thienopyrimidine
• Lapatinib
• ErbB Receptors
• Receptor, ErbB-2

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Cell Line, Tumor
• Cell Proliferation
• Chemistry, Pharmaceutical (methods)
• Drug Design
• Drug Screening Assays, Antitumor
• Enzyme Inhibitors (pharmacology)
• ErbB Receptors (chemistry)
• Humans
• Inhibitory Concentration 50
• Lapatinib
• Models, Chemical
• Molecular Conformation
• Pyrimidines (chemistry)
• Quinazolines (pharmacology)
• Receptor, ErbB-2 (antagonists & inhibitors)