Potent BRAF kinase inhibitors based on 2, 4, 5-trisubstituted imidazole with naphthyl and benzothiophene 4-substituents

D Niculescu-Duvaz, I Niculescu-Duvaz…

Index: Niculescu-Duvaz, Dan; Niculescu-Duvaz, Ion; Suijkerbuijk, Bart M.J.M.; Menard, Delphine; Zambon, Alfonso; Davies, Lawrence; Pons, Jean-Francois; Whittaker, Steven; Marais, Richard; Springer, Caroline J. Bioorganic and Medicinal Chemistry, 2013 , vol. 21, # 5 p. 1284 - 1304

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Citation Number: 11

Abstract

The RAS–RAF–MEK–ERK pathway is hyperactivated in 30% of human cancers. BRAF is a serine–threonine kinase, belonging to this pathway that is mutated with high frequency in human melanoma and other cancers thus BRAF is an important therapeutic target in melanoma. We have designed inhibitors of BRAF based on 2, 4, 5-trisubstituted imidazoles with naphthyl and benzothiophene-4-substituents. Two compounds were discovered to be ...

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