Abstract
A series of carboxylic acids was prepared based on cyclohexylglycine scaffolds and tested for potency as matrix metalloproteinase (MMP) inhibitors. Detailed SAR for the series is reported for five enzymes within the MMP family, and a number of inhibitors such as compound 18 display low nanomolar potency for MMP-2 and MMP-13, while selectively sparing MMP-1 and MMP-7.
MeSH terms
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Animals
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Carboxylic Acids / chemical synthesis
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Carboxylic Acids / metabolism
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Carboxylic Acids / pharmacology
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Collagenases / metabolism
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology*
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Glycine / analogs & derivatives*
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Glycine / pharmacology*
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Inhibitory Concentration 50
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Matrix Metalloproteinase 1 / metabolism
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Matrix Metalloproteinase 13
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 3 / metabolism
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Matrix Metalloproteinase 7 / metabolism
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Matrix Metalloproteinase Inhibitors*
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Metalloendopeptidases / antagonists & inhibitors*
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Metalloendopeptidases / metabolism
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Protein Binding / physiology
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Rats
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Structure-Activity Relationship
Substances
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Carboxylic Acids
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Enzyme Inhibitors
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Matrix Metalloproteinase Inhibitors
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Collagenases
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Matrix Metalloproteinase 13
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Metalloendopeptidases
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Mmp13 protein, rat
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Matrix Metalloproteinase 3
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Matrix Metalloproteinase 7
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 1
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Glycine