title: Enhancement of EGFR tyrosine kinase inhibition by C-C multiple bonds-containing anilinoquinazolines.
abstract: A series of 4-anilinoquinazolines with C-C multiple bond substitutions at the 6-position were synthesized and investigated for their potential to inhibit epidermal growth factor receptor (EGFR) tyrosine kinase activity. Among the compounds synthesized, alkyne 6d and allenes 7d and 7f significantly inhibited EGFR tyrosine kinase activity. These compounds inhibited EGF-mediated phosphorylation of EGFR in A431 cells, resulting in cell-cycle arrest and apoptosis induction. The C-C multiple bonds substituted at the C-6 position of the anilinoquinazoline framework were essential for the significant inhibitory activity. Compounds with long carbon chains (n=3-6), such as 6c-f, 7c-f, 11, and 12, displayed prolonged inhibitory activity.
authors.affiliation: Department of Chemistry, Faculty of Science, Gakushuin University, Tokyo 171-8588, Japan.
authors.forename: Hyun Seung
authors.initials: HS
authors.lastname: Ban
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Wataru
authors.initials: W
authors.lastname: Nabeyama
authors.forename: Masako
authors.initials: M
authors.lastname: Hatori
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D015151:Immunoblotting; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors