Abstract
The structure-based design and progression of a screening lead to a 3nM factor VIIa/TF inhibitor with improved selectivity versus related enzymes is described.
MeSH terms
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Amidines / chemistry*
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Amidines / metabolism
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Amidines / pharmacology*
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Binding Sites
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Crystallography, X-Ray
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Drug Design
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Drug Evaluation, Preclinical
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Factor VIIa / antagonists & inhibitors*
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Factor VIIa / chemistry
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Factor VIIa / metabolism
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Humans
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Hydrogen Bonding
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Models, Molecular
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Phenylacetates / chemistry*
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Phenylacetates / metabolism
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Phenylacetates / pharmacology*
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Prothrombin Time
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Serine Proteinase Inhibitors / chemistry*
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Serine Proteinase Inhibitors / metabolism
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Serine Proteinase Inhibitors / pharmacology*
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Structure-Activity Relationship
Substances
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5-(5-amidinoindol-2-yl)-6-hydroxy-3-((3-nitrophenyl)phenyl)acetic acid
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Amidines
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Phenylacetates
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Serine Proteinase Inhibitors
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Factor VIIa