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

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 tum...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2011-01, Vol.21 (2), p.781-785
Hauptverfasser:	Fink, Brian E., Norris, Derek, Mastalerz, Harold, Chen, Ping, Goyal, Bindu, Zhao, Yufen, Kim, Soong-Hoon, Vite, Gregory D., Lee, Francis Y., Zhang, Hongjian, Oppenheimer, Simone, Tokarski, John S., Wong, Tai W., Gavai, Ashvinikumar V.
Format:	Artikel
Sprache:	eng
Schlagworte:	aniline Animals Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Cell Line, Tumor Colonic Neoplasms - drug therapy EGFR HER2 Humans Kinase inhibitor Male Mice Mice, Inbred BALB C Models, Molecular Neoplasms - drug therapy Neoplasms - enzymology protein-tyrosine kinases Protein-Tyrosine Kinases - chemistry Protein-Tyrosine Kinases - pharmacokinetics Protein-Tyrosine Kinases - pharmacology Protein-Tyrosine Kinases - therapeutic use Pyrroles - chemistry Pyrroles - pharmacokinetics Pyrroles - pharmacology Pyrroles - therapeutic use Receptor, Epidermal Growth Factor - antagonists & inhibitors Receptor, Epidermal Growth Factor - metabolism Receptor, ErbB-2 - antagonists & inhibitors Receptor, ErbB-2 - metabolism Stomach Neoplasms - drug therapy Triazines - chemistry Triazines - pharmacokinetics Triazines - pharmacology Triazines - therapeutic use Xenograft Model Antitumor Assays
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Zusammenfassung:	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. 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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2010.11.100