Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series

Autor:	Kimberly G. Petrov, Ann Louise Walker, Yu Guo, Malcolm Clive Carter, David W. Rusnak, Scott Howard Dickerson, Robert A. Mook, Cassandra A. Gauthier, Edgar R. Wood, Karen Lackey, G. Stuart Cockerill, Yue-Mei Zhang
Rok vydání:	2006
Předmět:	Models Molecular Receptor ErbB-2 Clinical Biochemistry Pharmaceutical Science Lapatinib Biochemistry Inhibitory Concentration 50 Structure-Activity Relationship ErbB Cell Line Tumor Drug Discovery medicine Humans Structure–activity relationship Furans skin and connective tissue diseases Receptor Protein Kinase Inhibitors Molecular Biology Molecular Structure biology Chemistry Organic Chemistry Enzyme assay Cell biology ErbB Receptors Enzyme inhibitor Quinazolines biology.protein Molecular Medicine Signal transduction Tyrosine kinase medicine.drug
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 16:4686-4691
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2006.05.090
Popis:	Synthetic modifications on a 6-furanylquinazoline scaffold to optimize the dual ErbB-1/ErbB-2 tyrosine kinase inhibition afforded consistent SAR whereby a 4-(3-fluorobenzyloxy)-3-haloanilino provided the best enzyme potency and cellular selectivity. Changes made to the 6-furanyl group had little impact on the enzyme activity, but appeared to dramatically affect the cellular efficacy. The discovery of lapatinib emerged from this work.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fb0e36c5b474465ea5bf127c87c05182 https://doi.org/10.1016/j.bmcl.2006.05.090 Zobrazit plný text záznamu Full Text from ScienceDirect