Abstract
A series of compounds was designed and prepared as inhibitors of interleukin-1beta converting enzyme (ICE), also known as caspase-1. These inhibitors, which employ a diphenyl ether sulfonamide, were designed to improve potency by forming favorable interactions between the diphenyl ether rings and the prime side hydrophobic region. An X-ray crystal structure of a representative member of the diphenyl ether sulfonamide series bound to the active site of caspase-1 was obtained.
MeSH terms
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Caspase 1 / metabolism
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Caspase Inhibitors*
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Drug Design
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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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Ethers / chemical synthesis*
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Ethers / chemistry
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Ethers / pharmacology
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Models, Molecular
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis*
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Sulfonamides / chemistry
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Sulfonamides / pharmacology
Substances
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Caspase Inhibitors
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Enzyme Inhibitors
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Ethers
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Sulfonamides
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diphenyl ether sulfonamide
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Caspase 1