Abstract
The serine protease matriptase-2 has attracted much attention as a potential target for the treatment of iron overload diseases. In this study, a series of 27 symmetric, achiral bisbenzamidines was evaluated for inhibitory activity against human matriptase-2, against the closely related enzyme human matriptase, as well as against human thrombin, bovine factor Xa and human trypsin. The conformationally restricted piperazine derivative 19 and the oxamide-derived bisbenzamidine 1 were identified as the most potent inhibitors of this series for matriptase-2 and matriptase, respectively.
Keywords:
Bisbenzamidines; Matriptase-2; Serine proteases.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Benzamidines / chemical synthesis
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Benzamidines / chemistry
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Benzamidines / pharmacology*
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Cattle
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Dose-Response Relationship, Drug
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Factor Xa / metabolism
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Humans
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Membrane Proteins / antagonists & inhibitors*
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Membrane Proteins / metabolism
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Molecular Structure
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Serine Endopeptidases / metabolism
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Serine Proteinase Inhibitors / chemical synthesis
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Serine Proteinase Inhibitors / chemistry
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Serine Proteinase Inhibitors / pharmacology*
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Structure-Activity Relationship
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Thrombin / antagonists & inhibitors
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Thrombin / metabolism
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Trypsin / metabolism
Substances
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Benzamidines
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Membrane Proteins
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Serine Proteinase Inhibitors
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Serine Endopeptidases
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matriptase 2
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Trypsin
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Thrombin
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Factor Xa