1309773-87-2Relevant articles and documents
Discovery of 7-aryl-substituted (1,5-naphthyridin-4-yl)ureas as Aurora kinase inhibitors
Defaux, Julien,Antoine, Maud,Le Borgne, Marc,Schuster, Tilmann,Seipelt, Irene,Aicher, Babette,Teifel, Michael,Guenther, Eckhard,Gerlach, Matthias,Marchand, Pascal
, p. 217 - 232 (2014/01/17)
As part of our research projects to identify new chemical entities of biological interest, we developed a synthetic approach and the biological evaluation of (7-aryl-1,5-naphthyridin-4-yl)ureas as a novel class of Aurora kinase inhibitors for the treatment of malignant diseases based on pathological cell proliferation. 1,5-Naphthyridine derivatives showed excellent inhibitory activities toward Aurora kinases A and B, and the most active compound, 1-cyclopropyl-3-[7-(1-methyl-1H-pyrazol-4-yl)-1,5-naphthyridin-4-yl]urea (49), displayed IC50 values of 13 and 107 nM against Aurora kinases A and B, respectively. In addition, the selectivity toward a panel of seven cancer-related protein kinases was highlighted. In vitro ADME properties were also determined in order to rationalize the difficulties in correlating antiproliferative activity with Aurora kinase inhibition. Finally, the good safety profile of these compounds imparts promising potential for their further development as anticancer agents. Promising Aurora inhibitors: Herein we report a series of (7-aryl-1,5-naphthyridin-4-yl)ureas as a novel class of nanomolar-range Aurora kinase inhibitors. The described derivatives have good cell-penetration parameters and safety profiles, but their efficiency toward signaling pathways are insufficient to induce cell death. We also highlight their selectivity toward a panel of seven cancer-related protein kinases. Copyright
Novel Naphthyridine derivatives and the use thereof as kinase inhibitors
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Page/Page column 32, (2011/06/26)
The present invention relates to kinase modulators of the naphthyridine type and to the preparation and use thereof as medicaments for the modulation of misdirected cellular signal transduction processes, in particular for influencing the function of tyro