5-Substituted 4-anilinoquinazolines as potent, selective and orally active inhibitors of erbB2 receptor tyrosine kinase.
Starting from a 6,7-substituted quinazoline lead 4, optimisation of 5-substituted quinazolines containing an extended aniline motif led to potent and selective inhibitors of erbB2 receptor tyrosine kinase, and a representative compound 12a inhibited tumour growth in a mouse xenograft model.
Ballard
Peter
P
Cancer and Infection Research, AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK.
Bradbury
Robert H
RH
Hennequin
Laurent F A
LF
Hickinson
D Mark
DM
Johnson
Paul D
PD
Kettle
Jason G
JG
Klinowska
Teresa
T
Morgentin
Remy
R
Ogilvie
Donald J
DJ
Olivier
Annie
A
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011799:Quinazolines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; C498804:Erbb2ip protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011799:Quinazolines