Novel pyrrolo[2,1-f][1,2,4]triazin-4-amines: Dual inhibitors of EGFR and HER2 protein tyrosine kinases

  • Bioorg Med Chem Lett. 2011 Jan 15;21(2):781-5. doi: 10.1016/j.bmcl.2010.11.100.
Brian E Fink  1 ,  Derek Norris ,  Harold Mastalerz ,  Ping Chen ,  Bindu Goyal ,  Yufen Zhao ,  Soong-Hoon Kim ,  Gregory D Vite ,  Francis Y Lee ,  Hongjian Zhang ,  Simone Oppenheimer ,  John S Tokarski ,  Tai W Wong ,  Ashvinikumar V Gavai
Affiliations
  • 1. Department of Oncology Chemistry, Discovery Biology, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, United States. [email protected]
PMID: 21177105 DOI: 10.1016/j.bmcl.2010.11.100
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.