title: Synthesis and evaluation of aniline headgroups for alkynyl thienopyrimidine dual EGFR/ErbB-2 kinase inhibitors.
abstract: Aniline 'headgroups' were synthesized and incorporated into an alkynyl thienopyrimidine series of EGFR and ErbB-2 inhibitors. Potent inhibition of enzyme activity and cellular proliferation was observed. In certain instances, protein binding was reduced and oral exposure was found to be somewhat improved relative to compounds containing the reference aniline.
authors.affiliation: GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA.
authors.forename: Alex G
authors.initials: AG
authors.lastname: Waterson
authors.forename: Kimberly G
authors.initials: KG
authors.lastname: Petrov
authors.forename: Keith R
authors.initials: KR
authors.lastname: Hornberger
authors.forename: Robert D
authors.initials: RD
authors.lastname: Hubbard
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Sammond
authors.forename: Stephon C
authors.initials: SC
authors.lastname: Smith
authors.forename: Hamilton D
authors.initials: HD
authors.lastname: Dickson
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Caferro
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Hinkle
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Stevens
authors.forename: Scott H
authors.initials: SH
authors.lastname: Dickerson
authors.forename: David W
authors.initials: DW
authors.lastname: Rusnak
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Spehar
authors.forename: Edgar R
authors.initials: ER
authors.lastname: Wood
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Griffin
authors.forename: David E
authors.initials: DE
authors.lastname: Uehling
mesh_terms: D000284:Administration, Oral; D000814:Aniline Compounds / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D066246:ErbB Receptors; D006131:Growth Inhibitors; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D018719:Erb-b2 Receptor Tyrosine Kinases; C476003:thienopyrimidine; C512478:EGFR protein, human; C023650:aniline