Document Report Card
Basic Information
ID: ALA1146624
Journal: Bioorg Med Chem Lett
Title: Synthesis and evaluation of 4-anilino-6,7-dialkoxy-3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade.
Authors: Berger D, Dutia M, Powell D, Wu B, Wissner A, Boschelli DH, Floyd MB, Zhang N, Torres N, Levin J, Du X, Wojciechowicz D, Discafani C, Kohler C, Kim SC, Feldberg LR, Collins K, Mallon R.
Abstract: 4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)]anilino-6,7-diethoxy-3-quinolinecarbonitrile (3) was identified as a MEK1 kinase inhibitor with exceptional activity against LoVo cells. The structure-activity relationships of the C-4 aniline substituents were explored, and water-solubilizing groups were added at the C-7 position to improve physical properties. Secondary cellular assays revealed that a compound possessing the appropriate aniline substituents inhibited MEK1 as well as MAPK phosphorylation, thereby acting as a dual inhibitor of the Ras-MAPK signaling cascade.
CiteXplore: 12941327