Abstract
The discovery of a highly potent and selective tissue factor/factor VIIa inhibitor is described. Upon oral administration of its double prodrug in the guinea pig, a dose-dependent antithrombotic effect is observed in an established model of arterial thrombosis without prolonging bleeding time. The pharmacodynamic properties of this selective inhibitor are compared to the behaviour of a mixed factor VIIa/factor Xa inhibitor.
MeSH terms
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Administration, Oral
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Animals
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Anticoagulants / chemical synthesis*
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Anticoagulants / pharmacology*
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Bleeding Time
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Blood Coagulation Factor Inhibitors / chemical synthesis*
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Blood Coagulation Factor Inhibitors / pharmacology*
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical
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Factor VIIa / antagonists & inhibitors*
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Guinea Pigs
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Humans
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Models, Molecular
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Molecular Structure
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Prodrugs / chemical synthesis
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Prodrugs / pharmacology
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Rats
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Stereoisomerism
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Structure-Activity Relationship
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Thromboplastin / antagonists & inhibitors*
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Thrombosis / drug therapy
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Thrombosis / prevention & control
Substances
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Anticoagulants
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Blood Coagulation Factor Inhibitors
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Prodrugs
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Thromboplastin
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Factor VIIa