Abstract
5-Benzylidene-2-thioxo-thiazolidin-4-one inhibitors of ADAMTS-5 (Aggrecanase-2) have been prepared via commercially available starting materials. The identified compounds show micromolar ADAMTS-5 potency and demonstrate SAR trends for both the aryl group and thioxothiazolidinone zinc chelator. This series of compounds represents steps toward a metalloprotease inhibitor as a disease-modifying osteoarthritis drug.
MeSH terms
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ADAM Proteins / antagonists & inhibitors*
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ADAMTS5 Protein
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Chelating Agents
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use
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Humans
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Metalloproteases / antagonists & inhibitors
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Osteoarthritis / drug therapy
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Structure-Activity Relationship
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Thiazolidinediones / chemical synthesis*
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Thiazolidinediones / pharmacology*
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Zinc
Substances
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Chelating Agents
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Enzyme Inhibitors
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Thiazolidinediones
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Metalloproteases
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ADAM Proteins
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ADAMTS5 Protein
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ADAMTS5 protein, human
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Zinc