title: Synthesis of water soluble bis-triazenoquinazolines: an unusual predicted mode of binding to the epidermal growth factor receptor tyrosine kinase.
abstract: A novel type of 3,3-disubstituted bis-triazenes containing an ethylaminoethyl linker flanked by two identical anilinoquinazoline ring was synthesized. These model molecules contained an N-ethylaminomorpholine moiety designed to enhance water solubility. Despite their significant bulkiness, they blocked epidermal growth factor receptor (EGFR) tyrosine kinase in a dose-dependent manner with IC(50) values in low micromolar range. Molecular modeling to predict the interactions of the molecule with the ATP binding site of EGFR suggests that the N-ethylaminomorpholine side chain plays a binding role.
authors.affiliation: Cancer Drug Research Laboratory, Department of Medicine, Division of Medical Oncology, McGill University/Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC H3A 1A1, Canada.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Larroque
authors.forename: Brad
authors.initials: B
authors.lastname: Peori
authors.forename: Christopher
authors.initials: C
authors.lastname: Williams
authors.forename: You Qiang
authors.initials: YQ
authors.lastname: Fang
authors.forename: Qiyu
authors.initials: Q
authors.lastname: Qiu
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Rachid
authors.forename: Bertrand J
authors.initials: BJ
authors.lastname: Jean-Claude
mesh_terms: D066246:ErbB Receptors / Q000737:chemistry* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry; D012995:Solubility; D014226:Triazenes / Q000138:chemical synthesis* / Q000737:chemistry; D014867:Water
chemical_list: D011799:Quinazolines; D014226:Triazenes; D014867:Water; D066246:ErbB Receptors