Abstract
A series of p-aminomethylphenylalanine derivatives were investigated as novel thrombin inhibitors. This study led to potent inhibitors of thrombin (Ki up to 3.3 nM) that are trypsin-selective, highly orally bioavailable in rats, and highly permeable across Caco-2 cells. The P1 benzylamine binding mode in the thrombin active site was identified by X-ray crystallographic analysis.
MeSH terms
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Animals
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Benzylamines / chemistry*
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Biological Availability
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Caco-2 Cells
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Crystallography, X-Ray
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Humans
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Kinetics
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Models, Molecular
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Rats
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Serine Proteinase Inhibitors / chemical synthesis
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Serine Proteinase Inhibitors / pharmacokinetics*
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Serine Proteinase Inhibitors / pharmacology
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Thrombin / antagonists & inhibitors*
Substances
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Benzylamines
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Serine Proteinase Inhibitors
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benzylamine
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Thrombin