Abstract
Although thrombin has been extensively researched with many examples of potent and selective inhibitors, the key characteristics of oral bioavailability and long half-life have been elusive. We report here a novel series non-peptidic phenyl-based, highly potent, highly selective and orally bioavailable thrombin inhibitors using oxyguanidines as guanidine-mimetics.
MeSH terms
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Administration, Oral
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Animals
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Benzene Derivatives / chemistry*
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Benzene Derivatives / pharmacokinetics
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Benzene Derivatives / pharmacology*
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Biological Availability
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Caco-2 Cells
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Dogs
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Guanidines / chemistry*
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Guanidines / pharmacokinetics
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Guanidines / pharmacology*
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Humans
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Mice
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Microsomes / drug effects
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Rats
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Serine Endopeptidases / drug effects
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Serine Proteinase Inhibitors / pharmacology
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Structure-Activity Relationship
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Thrombin / antagonists & inhibitors*
Substances
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Benzene Derivatives
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Guanidines
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Serine Proteinase Inhibitors
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Serine Endopeptidases
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Thrombin