title: The discovery of highly selective erbB2 (Her2) inhibitors for the treatment of cancer.
abstract: The synthesis and biological evaluation of potent and selective inhibitors of the erbB2 kinase is presented. Based on the 4-anilinoquinazoline chemotype, the syntheses of several new series of erbB2 inhibitors are described with quinazoline and pyrido[4,3-d]pyrimidine cores. The vast majority of these compounds are found to be >100x selective over the closely related EGFR kinase. Two lead compounds are further shown to have low clearance and moderate bioavailability in rat.
authors.affiliation: Pfizer, Inc., PGRD Groton, MS-8220-2203 Eastern Point Road, Groton, CT 06340, USA. blaise.lippa@pfizer.com
authors.forename: Blaise
authors.initials: B
authors.lastname: Lippa
authors.forename: Goss S
authors.initials: GS
authors.lastname: Kauffman
authors.forename: Joel
authors.initials: J
authors.lastname: Arcari
authors.forename: Tricia
authors.initials: T
authors.lastname: Kwan
authors.forename: Jinshan
authors.initials: J
authors.lastname: Chen
authors.forename: William
authors.initials: W
authors.lastname: Hungerford
authors.forename: Samit
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Xumiao
authors.initials: X
authors.lastname: Zhao
authors.forename: Courtney
authors.initials: C
authors.lastname: Williams
authors.forename: Jun
authors.initials: J
authors.lastname: Xiao
authors.forename: Leslie
authors.initials: L
authors.lastname: Pustilnik
authors.forename: Chunyan
authors.initials: C
authors.lastname: Su
authors.forename: James D
authors.initials: JD
authors.lastname: Moyer
authors.forename: Ling
authors.initials: L
authors.lastname: Ma
authors.forename: Mary
authors.initials: M
authors.lastname: Campbell
authors.forename: Stefanus
authors.initials: S
authors.lastname: Steyn
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D045744:Cell Line, Tumor; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases