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
Journal of Medicinal Chemistry2011Vol. 54(20), pp. 7066–7083
Citations Over TimeTop 10% of 2011 papers
Vito Guagnano, Pascal Furet, Carsten Spanka, Vincent Bordas, Mickaël Le Douget, Christelle Stamm, Josef Brueggen, Michael Rugaard Jensen, Christian Schnell, Herbert Schmid, Markus Wartmann, Joerg Berghausen, Peter Drueckes, Alfred Zimmerlin, Dirksen E. Bussiere, Jeremy Murray, Diana Graus Porta
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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