title: Novel tricyclic azepine derivatives: Biological evaluation of pyrimido[4,5-b]-1,4-benzoxazepines, thiazepines, and diazepines as inhibitors of the epidermal growth factor receptor tyrosine kinase.
abstract: Novel tricyclic derivatives containing an oxazepine, thiazepine, or diazepine ring were studied for their EGFR tyrosine kinase inhibitory activity. While the oxazepines were in general more potent than thiazepines, the diazepines displayed somewhat different structure-activity relationships. Moreover, the diazepines, in contrast to the oxazepines, showed appreciable inhibitory activity against the KDR tyrosine kinase. Furthermore, both oxazepines and diazepines demonstrated significant ability to inhibit autophosphorylation of EGFR in DiFi cells (generally, IC(50) values in the single-digit micromolar to submicromolar range).
authors.affiliation: Department of Chemistry, ImClone Systems Incorporated, 710 Parkside Avenue, Suite 2, Brooklyn, NY 11226, USA. leon.smith@bms.com
authors.forename: Leon
authors.initials: L
authors.lastname: Smith
authors.forename: Wai C
authors.initials: WC
authors.lastname: Wong
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Kiselyov
authors.forename: Sabina
authors.initials: S
authors.lastname: Burdzovic-Wizemann
authors.forename: Yunyu
authors.initials: Y
authors.lastname: Mao
authors.forename: Yongjiang
authors.initials: Y
authors.lastname: Xu
authors.forename: Matthew A J
authors.initials: MA
authors.lastname: Duncton
authors.forename: Ki
authors.initials: K
authors.lastname: Kim
authors.forename: Evgueni L
authors.initials: EL
authors.lastname: Piatnitski
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: Doody
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Robin L
authors.initials: RL
authors.lastname: Rosler
authors.forename: Daniel
authors.initials: D
authors.lastname: Milligan
authors.forename: John
authors.initials: J
authors.lastname: Columbus
authors.forename: Chris
authors.initials: C
authors.lastname: Balagtas
authors.forename: Sui Ping
authors.initials: SP
authors.lastname: Lee
authors.forename: Andrey
authors.initials: A
authors.lastname: Konovalov
authors.forename: Yaron R
authors.initials: YR
authors.lastname: Hadari
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D001381:Azepines; D006575:Heterocyclic Compounds, 3-Ring; D009363:Neoplasm Proteins; D066246:ErbB Receptors; D040301:Vascular Endothelial Growth Factor Receptor-2