Abstract
The solid-phase synthesis of substituted 1,2,4-triazoles tethered to a 4-mercaptopyrrolidine core 1 is described. This novel class of non-peptidic, Zn(2+) metallo-protease inhibitors was found to have inhibitory activity for the endothelin converting enzyme (ECE-1). The SAR of the substitution pattern in 1 is discussed.
MeSH terms
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Endothelin-Converting Enzymes
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Humans
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Inhibitory Concentration 50
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Metalloendopeptidases / antagonists & inhibitors
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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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Pyrrolidines / chemical synthesis*
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Pyrrolidines / chemistry*
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Pyrrolidines / pharmacology
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Structure-Activity Relationship
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Triazoles / chemical synthesis*
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Triazoles / chemistry*
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Triazoles / pharmacology
Substances
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Protease Inhibitors
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Pyrrolidines
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Triazoles
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Aspartic Acid Endopeptidases
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Metalloendopeptidases
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ECE1 protein, human
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Endothelin-Converting Enzymes