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ID: ALA1667830
Journal: Bioorg Med Chem Lett
Title: Non-oxime inhibitors of B-Raf(V600E) kinase.
Authors: Ren L, Wenglowsky S, Miknis G, Rast B, Buckmelter AJ, Ely RJ, Schlachter S, Laird ER, Randolph N, Callejo M, Martinson M, Galbraith S, Brandhuber BJ, Vigers G, Morales T, Voegtli WC, Lyssikatos J.
Abstract: The development of inhibitors of B-Raf(V600E) serine-threonine kinase is described. Various head-groups were examined to optimize inhibitor activity and ADME properties. Several of the head-groups explored, including naphthol, phenol and hydroxyamidine, possessed good activity but had poor pharmacokinetic exposure in mice. Exposure was improved by incorporating more metabolically stable groups such as indazole and tricyclic pyrazole, while indazole could also be optimized for good cellular activity.
CiteXplore: 21251822