Abstract
The activated Factor VII/tissue factor complex (FVIIa/TF) plays a key role in the formation of blood clots. Inhibition of this complex may lead to new antithrombotic drugs. An X-ray crystal structure of a fluoropyridine-based FVIIa/TF inhibitor bound in the active site of the enzyme complex suggested that incorporation of substitution at the 5-position of the hydroxybenzoic acid side chain could lead to the formation of more potent inhibitors through interactions with the S1'/S2' pocket.
MeSH terms
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Binding Sites
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Crystallography, X-Ray
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Factor VIIa / antagonists & inhibitors
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Factor VIIa / chemistry*
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Factor Xa Inhibitors
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Fibrinolytic Agents / chemical synthesis*
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Fibrinolytic Agents / chemistry
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Fibrinolytic Agents / pharmacology
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Humans
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Inhibitory Concentration 50
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Protein Binding
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Prothrombin Time
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Structure-Activity Relationship
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Thromboplastin / antagonists & inhibitors
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Thromboplastin / chemistry*
Substances
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Enzyme Inhibitors
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Factor Xa Inhibitors
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Fibrinolytic Agents
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Pyridines
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Thromboplastin
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Factor VIIa