title: New dual inhibitors of EGFR and HER2 protein tyrosine kinases.
abstract: A novel series of dual EGFR and HER2 inhibitors based on the pyrrolo[2,1-f][1,2,4]triazine nucleus is described. A general route toward their synthesis, which enables functionalization at multiple sites, has been developed. Biological evaluation in enzymatic and cell-based assays has identified a series of C-6 carbamates with potent biochemical and cellular activities.
authors.affiliation: Department of Oncology Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, NJ 08543-4000, USA. brian.fink@bms.com
authors.forename: Brian E
authors.initials: BE
authors.lastname: Fink
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Vite
authors.forename: Harold
authors.initials: H
authors.lastname: Mastalerz
authors.forename: John F
authors.initials: JF
authors.lastname: Kadow
authors.forename: Soong-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Leavitt
authors.forename: Karen
authors.initials: K
authors.lastname: Du
authors.forename: Donald
authors.initials: D
authors.lastname: Crews
authors.forename: Toomas
authors.initials: T
authors.lastname: Mitt
authors.forename: Tai W
authors.initials: TW
authors.lastname: Wong
authors.forename: John T
authors.initials: JT
authors.lastname: Hunt
authors.forename: Dolatrai M
authors.initials: DM
authors.lastname: Vyas
authors.forename: John S
authors.initials: JS
authors.lastname: Tokarski
mesh_terms: D001665:Binding Sites; D002219:Carbamates / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D002219:Carbamates; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D014227:Triazines