Abstract
A series of alpha-sulfone piperidine hydroxamate TACE inhibitors 11a-n bearing a quinolinyl methyl P1' group was prepared, and their activity was compared to analogous alpha- and beta-sulfone piperidine hydroxamates with a butynyloxy P1' group. The quinolinyl methyl P1' group affords increased inhibitory enzyme activity relative to the corresponding butynyloxy P1' analogs in the alpha-sulfone piperidine hydroxamate series, and greater selectivity than the corresponding butynyloxy P1' analogs in the beta-sulfone piperidine hydroxamate series.
MeSH terms
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ADAM Proteins / antagonists & inhibitors*
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ADAM Proteins / metabolism
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ADAM17 Protein
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Animals
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Humans
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Hydroxamic Acids / chemical synthesis*
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Hydroxamic Acids / chemistry
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Hydroxamic Acids / pharmacology
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Mice
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Piperidines / chemical synthesis
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Piperidines / chemistry*
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology
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Sulfones / chemical synthesis
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Sulfones / chemistry*
Substances
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Hydroxamic Acids
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Piperidines
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Protease Inhibitors
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Sulfones
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piperidine
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ADAM Proteins
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ADAM17 Protein
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ADAM17 protein, human
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Adam17 protein, mouse