Abstract
Replacement of the highly basic benzamidine moiety with moderate basic amino-bicycloaryl moieties in a series of thrombin inhibitors related to NAPAMP provided potent enzyme inhibition and significant improvements in membrane transport and oral bioavailability.
MeSH terms
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Administration, Oral
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Anticoagulants / chemical synthesis
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Anticoagulants / pharmacology
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Antithrombins / chemical synthesis*
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Antithrombins / pharmacology
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Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Caco-2 Cells
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Cell Membrane Permeability
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Drug Design
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Humans
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Isoquinolines / chemical synthesis
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Isoquinolines / pharmacology
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Molecular Structure
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Piperidines / chemical synthesis
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Piperidines / pharmacology
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Serine Proteinase Inhibitors / chemical synthesis
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Serine Proteinase Inhibitors / pharmacology
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Thrombin / antagonists & inhibitors*
Substances
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Anticoagulants
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Antithrombins
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Bridged Bicyclo Compounds, Heterocyclic
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Isoquinolines
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Piperidines
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Serine Proteinase Inhibitors
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Thrombin