Abstract
NSC 333003 has been identified from the NCI Diversity Set as an inhibitor of the MDM2-p53 protein-protein interaction by in silico docking (virtual screening). Its potency and chemical characteristics render it well suited for lead optimization studies that can result in more potent analogs with improved drug-like properties. Its synthesis was achieved using an acid catalyzed condensation reaction from commercially available benzothiazole hydrazine and pyridyl phenyl ketone in refluxing methanol. Stereochemical implications for this compound are described.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Benzothiazoles / chemical synthesis
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Benzothiazoles / chemistry*
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Benzothiazoles / pharmacology
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Cell Line, Tumor
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Computer Simulation
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Crystallography, X-Ray
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Hydrazines / chemical synthesis
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Hydrazines / chemistry*
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Hydrazines / pharmacology
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Mice
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Molecular Conformation
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Protein Interaction Domains and Motifs
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Proto-Oncogene Proteins c-mdm2 / chemistry*
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Proto-Oncogene Proteins c-mdm2 / metabolism
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Stereoisomerism
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Structure-Activity Relationship
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Tumor Suppressor Protein p53 / chemistry*
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Tumor Suppressor Protein p53 / metabolism
Substances
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Benzothiazoles
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Enzyme Inhibitors
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Hydrazines
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NSC 333003
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Tumor Suppressor Protein p53
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2