Abstract
A series of 4-anilino-3-cyano-6,7-dialkoxyquinolines with different substituents attached to the 4-anilino group has been prepared that are potent MEK (MAP kinase kinase) inhibitors. The best activity is obtained when a phenyl or a thienyl group is attached to the para-position of the aniline through a hydrophobic linker, such as an oxygen, a sulfur, or a methylene group. The most active compounds show low nanomolar IC(50)'s against MEK (MAP kinase kinase), and have potent growth inhibitory activity in LoVo cells (human colon tumor line).
MeSH terms
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Aniline Compounds / chemistry
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Aniline Compounds / pharmacology*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Division / drug effects
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
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Quinolines / chemistry
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Quinolines / pharmacology*
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Structure-Activity Relationship
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Tumor Cells, Cultured
Substances
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Aniline Compounds
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Antineoplastic Agents
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Enzyme Inhibitors
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Quinolines
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Mitogen-Activated Protein Kinase Kinases