title: Thienopyrimidine-based dual EGFR/ErbB-2 inhibitors.
abstract: Two new series of potent and selective dual EGFR/ErbB-2 kinase inhibitors derived from novel thienopyrimidine cores have been identified. Isomeric thienopyrimidine cores were evaluated as isosteres for a 4-anilinoquinazoline core and several analogs containing the thieno[3,2-d]pyrimidine core showed anti-proliferative activity with IC(50) values less than 1 microM against human tumor cells in vitro.
authors.affiliation: Department of Oncology Medicinal Chemistry, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. tara.r.rheault@gsk.com
authors.forename: Tara R
authors.initials: TR
authors.lastname: Rheault
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Caferro
authors.forename: Scott H
authors.initials: SH
authors.lastname: Dickerson
authors.forename: Kelly H
authors.initials: KH
authors.lastname: Donaldson
authors.forename: Michael D
authors.initials: MD
authors.lastname: Gaul
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Goetz
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mullin
authors.forename: Octerloney B
authors.initials: OB
authors.lastname: McDonald
authors.forename: Kimberly G
authors.initials: KG
authors.lastname: Petrov
authors.forename: David W
authors.initials: DW
authors.lastname: Rusnak
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Shewchuk
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Spehar
authors.forename: Anne T
authors.initials: AT
authors.lastname: Truesdale
authors.forename: Dana E
authors.initials: DE
authors.lastname: Vanderwall
authors.forename: Edgar R
authors.initials: ER
authors.lastname: Wood
authors.forename: David E
authors.initials: DE
authors.lastname: Uehling
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D000077341:Lapatinib; D008956:Models, Chemical; D008968:Molecular Conformation; D011743:Pyrimidines / Q000737:chemistry*; D011799:Quinazolines / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D000077341:Lapatinib; D011743:Pyrimidines; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C476003:thienopyrimidine