Abstract
A series of functionalized aryl boronic acids were synthesized and evaluated as potential inhibitors of factor XIa. Crystal structures of the protein-inhibitor complexes led to the design and synthesis of second generation compounds showing single digit micromolar inhibition against FXIa and selectivity against thrombin, trypsin, and FXa.
MeSH terms
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Anticoagulants / chemical synthesis*
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Anticoagulants / pharmacology
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Binding Sites
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Boronic Acids / chemical synthesis*
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Boronic Acids / pharmacology*
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Crystallography, X-Ray
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Drug Design
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Factor XIa / antagonists & inhibitors*
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Humans
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Inhibitory Concentration 50
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Protein Binding
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Protein Conformation
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Serine Proteinase Inhibitors / chemical synthesis
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Serine Proteinase Inhibitors / pharmacology
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Structure-Activity Relationship
Substances
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Anticoagulants
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Boronic Acids
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Serine Proteinase Inhibitors
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Factor XIa