Abstract
The prevention of aggrecan (a key component of cartilage) cleavage via the inhibition of aggrecanase-1 may provide a unique opportunity to stop the progression of cartilage degradation in osteoarthritis. The evaluation of a series of biphenylsulfonamides resulted in the identification of the ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides analogs (19-21 and 24) with improved Agg-1 inhibition and MMP-2, MMP-13 activity.
MeSH terms
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ADAM Proteins / antagonists & inhibitors*
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ADAM Proteins / metabolism*
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ADAMTS4 Protein
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Cartilage / drug effects
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Cartilage / metabolism
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Humans
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Inhibitory Concentration 50
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Matrix Metalloproteinase 13 / metabolism
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Matrix Metalloproteinase 2 / metabolism
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Models, Chemical
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Molecular Conformation
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Osteoarthritis / drug therapy*
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Procollagen N-Endopeptidase / antagonists & inhibitors*
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Procollagen N-Endopeptidase / metabolism*
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Proteoglycans / chemistry
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Sulfonamides / chemical synthesis*
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Sulfonamides / pharmacology
Substances
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Proteoglycans
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Sulfonamides
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ADAM Proteins
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Matrix Metalloproteinase 13
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Procollagen N-Endopeptidase
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Matrix Metalloproteinase 2
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ADAMTS4 Protein