Abstract
A novel class of 1-[4-(1H-benzoimidazol-2-yl)-phenyl]-3-[4-(1H-benzoimidazol-2-yl)-phenyl]-ureas are described as potent inhibitors of heparanase. Among them are 1,3-bis-[4-(1H-benzoimidazol-2-yl)-phenyl]-urea (7a) and 1,3-bis-[4-(5,6-dimethyl-1H-benzoimidazol-2-yl)-phenyl]-urea (7d), which displayed good heparanase inhibitory activity (IC(50) 0.075-0.27 microM). Compound 7a showed good efficacy in a B16 metastasis model.
MeSH terms
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Animals
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Carbanilides / chemical synthesis
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Carbanilides / classification
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Carbanilides / pharmacology*
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Cell Line, Tumor
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Drug Design
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / classification
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Enzyme Inhibitors / pharmacology*
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Glucuronidase / antagonists & inhibitors*
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In Vitro Techniques
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Lung Neoplasms / drug therapy*
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Melanoma, Experimental / drug therapy*
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Melanoma, Experimental / secondary
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Mice
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Molecular Structure
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Molecular Weight
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Neoplasm Metastasis / drug therapy
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Structure-Activity Relationship
Substances
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Carbanilides
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Enzyme Inhibitors
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heparanase
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Glucuronidase