Synthesis and SAR of potent EGFR/erbB2 dual inhibitors.
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.
Zhang
Yue-Mei
YM
GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
Cockerill
Stuart
S
Guntrip
Stephen B
SB
Rusnak
David
D
Smith
Kathryn
K
Vanderwall
Dana
D
Wood
Edgar
E
Lackey
Karen
K
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
D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D006023:Glycoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human