Abstract
Using a furanylthiazole acetic acid as a starting point, a novel series of benzoxazol-5-yl acetic acid derivatives have been identified as heparanase inhibitors. Several compounds possess an IC50 of approximately 200 nM against heparanase, for example, trans 2-[4-[3-(3,4-dichlorophenylamino)-3-oxo-1-propenyl]-2-fluorophenyl]benzoxazol-5-yl acetic acid (16e). Several of the compounds show anti-angiogenic properties. Improvement to the DMPK profile of compounds has provided compounds of potential use in in vivo models.
MeSH terms
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Acetates / chemical synthesis
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Acetates / chemistry
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Acetates / pharmacology*
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Animals
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Benzoxazoles / chemical synthesis
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Benzoxazoles / chemistry
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Benzoxazoles / pharmacology*
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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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Glucuronidase / antagonists & inhibitors*
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Glucuronidase / blood
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Kinetics
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Mice
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Models, Molecular
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Molecular Structure
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Structure-Activity Relationship
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Thiazoles / chemical synthesis
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Thiazoles / chemistry
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Thiazoles / pharmacology*
Substances
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Acetates
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Benzoxazoles
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Enzyme Inhibitors
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Thiazoles
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heparanase
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Glucuronidase