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

作者：Guagnano Vito^*; Furet Pascal; Spanka Carsten; Bordas Vincent; Le Douget Mickael; Stamm Christelle; Brueggen Josef; Jensen Michael R; Schnell Christian; Schmid Herbert; Wartmann Markus; Berghausen Joerg; Drueckes Peter; Zimmerlin Alfred; Bussiere Dirksen; Murray Jeremy; Porta Diana Graus

来源：Journal of Medicinal Chemistry, 2011, 54(20): 7066-7083.

DOI：10.1021/jm2006222

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.

• 出版日期2011-10-27