Abstract
A novel quinoline derivative that selectively inhibits c-Met kinase was identified. The molecular design is based on a result of the analysis of a PF-2341066 (1)/c-Met cocrystal structure (PDB code: 2wgj). The kinase selectivity of the derivatives is discussed from the view point of the sequence homology of the kinases, the key interactions found in X-ray cocrystal structures, and the structure-activity relationship (SAR) obtained in this work.
Copyright 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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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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Cell Proliferation / drug effects
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Crizotinib
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Crystallography, X-Ray
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Humans
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Inhibitory Concentration 50
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Models, Molecular
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Oxyquinoline / chemical synthesis*
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Oxyquinoline / chemistry
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Oxyquinoline / pharmacology
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Piperidines / chemistry*
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Piperidines / pharmacology
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Protein Kinase Inhibitors / pharmacology*
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Proto-Oncogene Proteins c-met / antagonists & inhibitors*
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Pyrazoles
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Pyridines / chemistry*
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Pyridines / pharmacology
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Piperidines
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Protein Kinase Inhibitors
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Pyrazoles
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Pyridines
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Crizotinib
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Oxyquinoline
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Proto-Oncogene Proteins c-met