Abstract
The synthesis of a novel series of pyrimidin-4-yl-1H-imidazol-2-yl derivatives 7, 8, 9 and their antiproliferative activities against A375P human melanoma cell line and WM3629 cell line were described. Most compounds showed superior antiproliferative activities compared to Sorafenib, the well-known RAF inhibitor. Among them, 7a exhibited potent activities on both cell lines (IC(50)=0.62 and 4.49muM, respectively) and turned out to be a selective and potent CRAF inhibitor.
Copyright 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / therapeutic use
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Benzenesulfonates / chemistry
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Benzenesulfonates / therapeutic use
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Binding Sites
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Cell Line, Tumor
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Crystallography, X-Ray
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Drug Discovery
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / chemistry*
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Imidazoles / therapeutic use
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Melanoma / drug therapy*
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Niacinamide / analogs & derivatives
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Phenylurea Compounds
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / therapeutic use
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Protein Kinases / chemistry
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Protein Kinases / metabolism
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Proto-Oncogene Proteins c-raf / antagonists & inhibitors
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Proto-Oncogene Proteins c-raf / metabolism
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Pyridines / chemistry
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Pyridines / therapeutic use
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry*
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Pyrimidines / therapeutic use
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Sorafenib
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Benzenesulfonates
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Imidazoles
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Phenylurea Compounds
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Protein Kinase Inhibitors
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Pyridines
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Pyrimidines
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Niacinamide
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Sorafenib
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Protein Kinases
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Proto-Oncogene Proteins c-raf
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pyrimidine