Abstract
Inhibition of coagulation proteases such as thrombin, fXa, and fVIIa has been a focus of ongoing research to produce safe and effective antithrombotic agents. Herein, we describe a unique zinc-mediated chelation strategy to streamline the discovery of potent inhibitors of fIIa, fXa, and fVIIa. SAR studies that led to the development of selective inhibitors of fXa will also be detailed.
MeSH terms
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Anticoagulants / chemistry*
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Anticoagulants / pharmacology
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Blood Coagulation / drug effects*
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Blood Coagulation / physiology
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Chelating Agents / chemistry*
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Crystallography, X-Ray
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Factor VII / antagonists & inhibitors
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Factor Xa Inhibitors
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / pharmacology
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Structure-Activity Relationship
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Thrombin / antagonists & inhibitors
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Zinc / chemistry*
Substances
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Anticoagulants
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Chelating Agents
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Factor Xa Inhibitors
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Protease Inhibitors
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Factor VII
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Thrombin
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Zinc