title: Synthesis and SAR of potent EGFR/erbB2 dual inhibitors.
abstract: A series of 6-alkoxy-4-anilinoquinazoline compounds was prepared and evaluated for in vitro inhibition of the erbB2 and EGFR kinase activity. The IC(50) values of the best compounds were below 0.10 uM. Further, several of these compounds inhibit the growth of erbB2 and EGFR over-expressing tumor cell lines at concentrations below 1 uM.
authors.affiliation: GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Yue-Mei
authors.initials: YM
authors.lastname: Zhang
authors.forename: Stuart
authors.initials: S
authors.lastname: Cockerill
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Guntrip
authors.forename: David
authors.initials: D
authors.lastname: Rusnak
authors.forename: Kathryn
authors.initials: K
authors.lastname: Smith
authors.forename: Dana
authors.initials: D
authors.lastname: Vanderwall
authors.forename: Edgar
authors.initials: E
authors.lastname: Wood
authors.forename: Karen
authors.initials: K
authors.lastname: Lackey
mesh_terms: D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D066246:ErbB Receptors; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D006023:Glycoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human