Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamin o]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase
By: Guagnano V, Furet P, Spanka C, Bordas V, Le Douget M, Stamm C, Brueggen J, Jensen MR, Schnell C, Schmid H, Wartmann M, Berghausen J, Drueckes P, Zimmerlin A, Bussiere D, Murray J, Graus Porta D.
Novartis Institute for BioMedical Research, CH-4002 Basel, Switzerland. vito.guagnano@novartis.com
J Med Chem. 2011 Oct 27; 54(20):7066-83. Epub 2011 Sep 21.
Novartis Institute for BioMedical Research, CH-4002 Basel, Switzerland. vito.guagnano@novartis.com
J Med Chem. 2011 Oct 27; 54(20):7066-83. Epub 2011 Sep 21.
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.
PMID: 21936542 [PubMed - indexed for MEDLINE] Source: National Library of Medicine.
