title: Novel pyrrolo[2,1-f][1,2,4]triazin-4-amines: Dual inhibitors of EGFR and HER2 protein tyrosine kinases.
abstract: A novel series of 5-((4-aminopiperidin-1-yl)methyl)-pyrrolo[2,1-f][1,2,4]triazin-4-amines with small aniline substituents at the C4 position were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. Compound 8l exhibited promising oral efficacy in both EGFR and HER2-driven human tumor xenograft models.
authors.affiliation: Department of Oncology Chemistry, Discovery Biology, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, United States. brian.fink@bms.com
authors.forename: Brian E
authors.initials: BE
authors.lastname: Fink
authors.forename: Derek
authors.initials: D
authors.lastname: Norris
authors.forename: Harold
authors.initials: H
authors.lastname: Mastalerz
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Bindu
authors.initials: B
authors.lastname: Goyal
authors.forename: Yufen
authors.initials: Y
authors.lastname: Zhao
authors.forename: Soong-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Vite
authors.forename: Francis Y
authors.initials: FY
authors.lastname: Lee
authors.forename: Hongjian
authors.initials: H
authors.lastname: Zhang
authors.forename: Simone
authors.initials: S
authors.lastname: Oppenheimer
authors.forename: John S
authors.initials: JS
authors.lastname: Tokarski
authors.forename: Tai W
authors.initials: TW
authors.lastname: Wong
authors.forename: Ashvinikumar V
authors.initials: AV
authors.lastname: Gavai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy; D014227:Triazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D011758:Pyrroles; D018719:Erb-b2 Receptor Tyrosine Kinases; D014227:Triazines