Abstract
A novel class of N-(4-{[4-(1H-benzoimidazol-2-yl)-arylamino]-methyl}-phenyl)-benzamides are described as inhibitors of the endo-beta-glucuronidase heparanase. Among them are N-(4-{[4-(1H-benzoimidazol-2-yl)-phenylamino]-methyl}-phenyl)-3-bromo-4-methoxy-benzamide (15h), and N-(4-{[5-(1H-benzoimidazol-2-yl)-pyridin-2-ylamino]-methyl}- phenyl)-3-bromo-4-methoxy-benzamide (23) which displayed good heparanase inhibitory activity (IC(50) 0.23-0.29 microM), with the latter showing oral exposure in mice.
MeSH terms
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Administration, Oral
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Animals
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Benzamides / administration & dosage
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Benzamides / chemistry
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Benzamides / pharmacology*
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Benzimidazoles / administration & dosage
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacology*
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Carbohydrate Conformation
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Carbohydrate Sequence
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Drug Design
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Drug Evaluation, Preclinical
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / chemistry
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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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Mice
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Models, Animal
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Molecular Sequence Data
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Molecular Structure
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Molecular Weight
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Structure-Activity Relationship
Substances
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Benzamides
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Benzimidazoles
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Enzyme Inhibitors
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heparanase
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Glucuronidase