title: Inhibitors of epidermal growth factor receptor tyrosine kinase: optimisation of potency and in vivo pharmacokinetics.
abstract: The structure-activity and structure-property relationships of anilinoquinazoline inhibitors of EGFR were investigated. Strategies to lower volume of distribution and shorten half-life through structure and pKa modulation are discussed.
authors.affiliation: AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Ballard
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bradbury
authors.forename: Craig S
authors.initials: CS
authors.lastname: Harris
authors.forename: Laurent F A
authors.initials: LF
authors.lastname: Hennequin
authors.forename: Mark
authors.initials: M
authors.lastname: Hickinson
authors.forename: Jason G
authors.initials: JG
authors.lastname: Kettle
authors.forename: Jane
authors.initials: J
authors.lastname: Kendrew
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: Emma J
authors.initials: EJ
authors.lastname: Williams
authors.forename: Ingrid
authors.initials: I
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005461:Fluorine / Q000737:chemistry; D000077156:Gefitinib; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D011799:Quinazolines / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D013844:Thiazoles; D005461:Fluorine; C027348:2-anilino-5-thiazolinone; D066246:ErbB Receptors; D000077156:Gefitinib