title: Novel C-5 aminomethyl pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.
abstract: Novel C-5 aminomethyl pyrrolotriazines were prepared and optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The homopiperazine, 1p, emerged as a key lead and it showed promising oral efficacy in EGFR and dual EGFR/HER2 driven human tumor xenograft models. It is hypothesized that the C-5 homopiperazine side chain binds in the ribose-phosphate portion of the ATP binding pocket.
authors: Department of Oncology Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492-1951, USA. harold.mastalerz@bms.com
authors: Harold
authors: H
authors: Mastalerz
authors: Ming
authors: M
authors: Chang
authors: Ashvinikumar
authors: A
authors: Gavai
authors: Walter
authors: W
authors: Johnson
authors: David
authors: D
authors: Langley
authors: Francis Y
authors: FY
authors: Lee
authors: Punit
authors: P
authors: Marathe
authors: Arvind
authors: A
authors: Mathur
authors: Simone
authors: S
authors: Oppenheimer
authors: James
authors: J
authors: Tarrant
authors: John S
authors: JS
authors: Tokarski
authors: Gregory D
authors: GD
authors: Vite
authors: Dolatrai M
authors: DM
authors: Vyas
authors: Henry
authors: H
authors: Wong
authors: Tai W
authors: TW
authors: Wong
authors: Hongjian
authors: H
authors: Zhang
authors: Guifen
authors: G
authors: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008744:Methylamines / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D008744:Methylamines; D011505:Protein-Tyrosine Kinases; D011758:Pyrroles; D018719:Erb-b2 Receptor Tyrosine Kinases; D014227:Triazines; C521361:aminomethyl pyrrolotriazine