Synthesis, SAR, and Evaluation of 4-[2,4-Difluoro-5-(cyclopropylcarbamoyl)phenylamino]pyrrolo[2,1- f][1,2,4]triazine-based VEGFR-2 kinase inhibitors

A new sub-family of pyrrolotriazine analogs was identified as the potent VEGFR-2 kinase inhibitors. Antitumor efficacy was observed with compound 37 against L2987 human lung carcinoma xenografts in athymic mice. Introduction of the 2,4-difluoro-5-(cyclopropylcarbamoyl)phenylamino group at the C-4 po...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2008-02, Vol.18 (4), p.1354-1358
Hauptverfasser: Cai, Zhen-wei, Wei, Donna, Borzilleri, Robert M., Qian, Ligang, Kamath, Amrita, Mortillo, Steven, Wautlet, Barri, Henley, Benjamin J., Jeyaseelan, Robert, Tokarski, John, Hunt, John T., Bhide, Rajeev S., Fargnoli, Joseph, Lombardo, Louis J.
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Sprache:eng
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Zusammenfassung:A new sub-family of pyrrolotriazine analogs was identified as the potent VEGFR-2 kinase inhibitors. Antitumor efficacy was observed with compound 37 against L2987 human lung carcinoma xenografts in athymic mice. Introduction of the 2,4-difluoro-5-(cyclopropylcarbamoyl)phenylamino group at the C-4 position of the pyrrolo[2,1- f][1,2,4] triazine scaffold led to the discovery of a novel sub-series of inhibitors of VEGFR-2 kinase activity. Subsequent SAR studies on the 1,3,5-oxadiazole ring appended to the C-6 position of this new sub-family of pyrrolotriazines resulted in the identification of low nanomolar inhibitors of VEGFR-2. Antitumor efficacy was observed with compound 37 against L2987 human lung carcinoma xenografts in athymic mice.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2008.01.012