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 F

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• 作者：Vito Guagnano ; Pascal Furet ; Carsten Spanka ; Vincent Bordas ; Micka毛l Le Douget ; Christelle Stamm ; Josef Brueggen ; Michael R. Jensen ; Christian Schnell ; Herbert Schmid ; Markus Wartmann ; Joerg Berghausen ; Peter Drueckes ; Alfred Zimmerlin ; Dirksen Bussiere ; Jeremy Murray ; Diana Graus Porta
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：October 27, 2011
• 年：2011
• 卷：54
• 期：20
• 页码：7066-7083
• 全文大小：1396K
• 年卷期：v.54,no.20(October 27, 2011)
• ISSN：1520-4804

文摘

A novel series of N-aryl-N鈥?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.