title: Synthesis and biological evaluation of a series of hydroxybenzylphenylamine derivatives as inhibitors of EGF receptor-associated tyrosine kinase activity.
abstract: In order to obtain non-degradable and more potent protein-tyrosine kinase inhibitors, derived from the 5-(2,5-dihydroxybenzyl)-aminosalicylates already described, we have developed a new series of 5-(2,5-dihydroxybenzyl)phenylamines. The compounds, diversely substituted on the phenyl ring by alcohol, nitrile, ether, ketone, amide and thioamide groups, were tested for their ability to inhibit epidermal growth factor (EGF) receptor-associated tyrosine kinase activity in vitro. They inhibit the phosphorylation of the peptide substrate RR-Src by the EGF receptor purified from ER 22 cells, with IC50 values in the range 0.02-0.45 microns. Several of these compounds inhibit EGF-dependent DNA synthesis in ER 22 cells with IC50 values of around 1 micron and furthermore their inhibition has been found to be specific for various protein kinases.
authors.affiliation: Département de Pharmacochimie Moléculaire et Structurale, Université René Descartes, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Bashiardes
authors.forename: P
authors.initials: P
authors.lastname: Mailliet
authors.forename: A
authors.initials: A
authors.lastname: Commercon
authors.forename: F
authors.initials: F
authors.lastname: Sounigo
authors.forename: J
authors.initials: J
authors.lastname: Boiziau
authors.forename: F
authors.initials: F
authors.lastname: Parker
authors.forename: B
authors.initials: B
authors.lastname: Tocque
authors.forename: B P
authors.initials: BP
authors.lastname: Roques
authors.forename: C
authors.initials: C
authors.lastname: Garbay
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006131:Growth Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D000814:Aniline Compounds; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D004247:DNA; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases