Abstract
Bicyclic piperazinone based thrombin inhibitors of general structure 2 were prepared and evaluated in vitro and in vivo. These inhibitors, having in common an electrophilic basic trans-cyclohexylamine P1 residue, displayed high thrombin affinity, high selectivity against trypsin and good in vivo efficacy in the rat arterial thrombosis model.
MeSH terms
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Animals
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Blood Coagulation Tests
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Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Combinatorial Chemistry Techniques
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Crystallography, X-Ray
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Disease Models, Animal
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Fibrinolytic Agents / chemical synthesis*
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Fibrinolytic Agents / pharmacology
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Lactams / chemical synthesis
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Lactams / pharmacology*
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Models, Molecular
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Rats
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Structure-Activity Relationship
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Thrombin / antagonists & inhibitors*
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Thrombosis / drug therapy
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Trypsin Inhibitors / pharmacology
Substances
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Bridged Bicyclo Compounds, Heterocyclic
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Fibrinolytic Agents
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Lactams
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Trypsin Inhibitors
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Thrombin