Abstract
A novel series of matriptase inhibitors based on previously identified tribasic 3-amidinophenylalanine derivatives was prepared. The C-terminal basic group was replaced by neutral residues to reduce the hydrophilicity of the inhibitors. The most potent compound 22 inhibits matriptase with a K(i) value of 0.43 nM, but lacks selectivity towards factor Xa. By combination with neutral N-terminal sulfonyl residues several potent thrombin inhibitors were identified, which had reduced matriptase affinity.
MeSH terms
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Administration, Oral
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Amidines / chemistry*
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Amidines / pharmacology
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Animals
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Factor Xa / metabolism
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Factor Xa Inhibitors
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Phenylalanine / analogs & derivatives
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Phenylalanine / chemistry*
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Phenylalanine / pharmacology
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Rats
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Serine Endopeptidases / chemistry*
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Serine Endopeptidases / metabolism
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Serine Proteinase Inhibitors / chemistry*
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Serine Proteinase Inhibitors / pharmacology
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Sulfonamides / chemistry*
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Sulfonamides / pharmacology
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Thrombin / antagonists & inhibitors
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Thrombin / metabolism
Substances
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Amidines
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Factor Xa Inhibitors
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Serine Proteinase Inhibitors
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Sulfonamides
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Phenylalanine
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Serine Endopeptidases
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matriptase
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Thrombin
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Factor Xa