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Discovery of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), A Potent and Selective Inhibitor of the Fibroblast Growth Factor Receptor Family of Receptor Tyrosine Kinase

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Guagnano, Vito, Furet, Pascal, Spanka, Carsten, Bordas, Vincent, Le Douget, Mickaël, Stamm, Christelle, Brueggen, Josef, Jensen, Michael R., Schnell, Christian, Schmid, Herbert, Wartmann, Markus, Berghausen, Joerg, Drueckes, Peter, Zimmerlin, Alfred, Bussiere, Dirksen, Murray, Jeremy, Graus Porta, Diana·2011·Journal of Medicinal Chemistry

DOI 10.1021/jm2006222

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Abstract

A novel series of N-aryl-N'-pyrimidin-4-yl ureas has been optimized to afford potent and selective inhibitors of the fibroblast growth factor receptor tyrosine kinases 1, 2, and 3 by rationally designing the substitution pattern of the aryl ring. On the basis of its in vitro profile, compound 1h (NVP-BGJ398) was selected for in vivo evaluation and showed significant antitumor activity in RT112 bladder cancer xenografts models overexpressing wild-type FGFR3. These results support the potential therapeutic use of 1h as a new anticancer agent.

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Self-citation
Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study
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See all 477

Authors: Guagnano, V., Furet, P., Spanka, C., Bordas, V., Le Douget, M., Stamm, C., Brueggen, J., Jensen, M. R., Schnell, C., Schmid, H., Wartmann, M., Berghausen, J., Drueckes, P., Zimmerlin, A., Bussiere, D., Murray, J., & Graus Porta, D.
Venue: Journal of Medicinal Chemistry
Publisher: American Chemical Society (ACS)
Published: 2011-09-21
Volume: 54
Issue: 20
Pages: 7066-7083
ISSN: 0022-2623 (ISSN-L)
1520-4804
DOI: 10.1021/jm2006222
OpenAlex: W2093090488
Cited by: 477
References: 48
FWCI: 7.99
Type: journal article
Language: en
Open access: green

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Discovery of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), A Potent and Selective Inhibitor of the Fibroblast Growth Factor Receptor Family of Receptor Tyrosine Kinase

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