Novel tricyclic pyrazole BRAF inhibitors with imidazole or furan central scaffolds

D Niculescu-Duvaz, I Niculescu-Duvaz…

Index: Niculescu-Duvaz, Dan; Niculescu-Duvaz, Ion; Suijkerbuijk, Bart M.J.M.; Menard, Delphine; Zambon, Alfonso; Nourry, Arnaud; Davies, Lawrence; Manne, Helen A.; Friedlos, Frank; Ogilvie, Lesley; Hedley, Douglas; Takle, Andrew K.; Wilson, David M.; Pons, Jean-Francois; Coulter, Tom; Kirk, Ruth; Cantarino, Neus; Whittaker, Steven; Marais, Richard; Springer, Caroline J. Bioorganic and Medicinal Chemistry, 2010 , vol. 18, # 18 p. 6934 - 6952

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Citation Number: 18

Abstract

V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole BRAF inhibitor bearing a phenylpyrazole group (dimethyl-[2-(4- {5-[4-(1H-pyrazol-3-yl)-phenyl]-4-pyridin-4-yl-1H-imidazol-2-yl}-phenoxy)-ethyl]-amine, 1a ...