title: 5-Substituted 4-anilinoquinazolines as potent, selective and orally active inhibitors of erbB2 receptor tyrosine kinase.
abstract: 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.
authors.affiliation: Cancer and Infection Research, AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Ballard
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bradbury
authors.forename: Laurent F A
authors.initials: LF
authors.lastname: Hennequin
authors.forename: D Mark
authors.initials: DM
authors.lastname: Hickinson
authors.forename: Paul D
authors.initials: PD
authors.lastname: Johnson
authors.forename: Jason G
authors.initials: JG
authors.lastname: Kettle
authors.forename: Teresa
authors.initials: T
authors.lastname: Klinowska
authors.forename: Remy
authors.initials: R
authors.lastname: Morgentin
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Ogilvie
authors.forename: Annie
authors.initials: A
authors.lastname: Olivier
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; C498804:Erbb2ip protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011799:Quinazolines