1. Academic Validation
  2. 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

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

  • J Med Chem. 2011 Oct 27;54(20):7066-83. doi: 10.1021/jm2006222.
Vito Guagnano 1 Pascal Furet Carsten Spanka Vincent Bordas Mickaël 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
Affiliations

Affiliation

  • 1 Novartis Institute for BioMedical Research, CH-4002 Basel, Switzerland. vito.guagnano@novartis.com
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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