Abstract
A novel non-peptidyl endothelin converting enzyme inhibitor was obtained through a pharmacophore analysis of known inhibitors and three-dimensional structure database search. Analogues of the new inhibitor were designed using the structure-activity relationship of known inhibitors and synthesized. In anesthetized rats, intraperitoneal administration of the analogues suppressed the pressor responses induced by big endothelin-1.
MeSH terms
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Animals
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Aspartic Acid Endopeptidases / chemical synthesis
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Aspartic Acid Endopeptidases / chemistry*
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Aspartic Acid Endopeptidases / pharmacology*
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Endothelin-Converting Enzymes
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Formazans / chemical synthesis
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Formazans / chemistry*
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Formazans / pharmacology*
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Hydrogen Bonding
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Metalloendopeptidases
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Models, Molecular
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Rats
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Tetrazoles / chemical synthesis
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Tetrazoles / chemistry*
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Tetrazoles / pharmacology*
Substances
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Enzyme Inhibitors
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Formazans
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Tetrazoles
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Aspartic Acid Endopeptidases
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Metalloendopeptidases
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Endothelin-Converting Enzymes