title: Neutral 5-substituted 4-anilinoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase.
abstract: Neutral 5-substituted 4-anilinoquinazolines addressed high in vivo clearance and phospholipidosis associated with previous basic compounds. A representative compound 8a inhibited tumor growth in a mouse xenograft model when co-administered with the cytochrome P450 inhibitor 1-aminobenzotriazole (ABT), and data are consistent with pharmacology primarily reflecting inhibition of erbB2 receptor tyrosine kinase.
authors.affiliation: Cancer and Infection Research, AstraZeneca, Mereside, Alderley Park, Macclesfield, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Ballard
authors.forename: Bernard C
authors.initials: BC
authors.lastname: Barlaam
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bradbury
authors.forename: Allan
authors.initials: A
authors.lastname: Dishington
authors.forename: Laurent F A
authors.initials: LF
authors.lastname: Hennequin
authors.forename: D Mark
authors.initials: DM
authors.lastname: Hickinson
authors.forename: Ian M
authors.initials: IM
authors.lastname: Hollingsworth
authors.forename: Jason G
authors.initials: JG
authors.lastname: Kettle
authors.forename: Teresa
authors.initials: T
authors.lastname: Klinowska
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Ogilvie
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Pearson
authors.forename: James S
authors.initials: JS
authors.lastname: Scott
authors.forename: Abid
authors.initials: A
authors.lastname: Suleman
authors.forename: Robin
authors.initials: R
authors.lastname: Whittaker
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Williams
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Lindsay
authors.initials: L
authors.lastname: Wright
mesh_terms: D000284:Administration, Oral; D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D049109:Cell Proliferation / Q000187:drug effects; D004285:Dogs; D004357:Drug Synergism; D051379:Mice; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D011799:Quinazolines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D014230:Triazoles / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D014230:Triazoles; C033020:1-aminobenzotriazole; C023650:aniline