Abstract
A series of 4-anilino-7-pyridyl-3-quinolinecarbonitriles was prepared as Src kinase inhibitors. A systematic SAR study of substitutions on both the pyridine ring and the 3-quinolinecarbonitrile core established the requirements for optimal activity. The lead compound, 17, showed potent activity in both the Src enzyme assay and cell assays, and demonstrated in vivo anti-tumor activity in a xenograft model.
MeSH terms
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Aminoquinolines / chemical synthesis
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Aminoquinolines / chemistry*
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Aminoquinolines / pharmacology
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Aniline Compounds / chemical synthesis
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Aniline Compounds / chemistry*
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Aniline Compounds / pharmacology
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Humans
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Mice
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Mice, Nude
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology
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Quinolines / chemical synthesis
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Quinolines / chemistry*
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Quinolines / pharmacology
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Rats
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Structure-Activity Relationship
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Xenograft Model Antitumor Assays
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src-Family Kinases / antagonists & inhibitors*
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src-Family Kinases / metabolism
Substances
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Aminoquinolines
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Aniline Compounds
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Quinolines
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src-Family Kinases