Abstract
Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating basic biaryl P4 groups, producing highly potent inhibitors with significant anticoagulant activities and encouraging oral pharmacokinetic profiles.
MeSH terms
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Animals
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Anticoagulants / chemistry
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Anticoagulants / pharmacokinetics
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Anticoagulants / pharmacology
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Bridged Bicyclo Compounds, Heterocyclic / chemistry*
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Bridged Bicyclo Compounds, Heterocyclic / pharmacokinetics
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Factor Xa Inhibitors*
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Hydrophobic and Hydrophilic Interactions
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Male
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Models, Molecular
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Pyrrolidinones / chemistry*
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Pyrrolidinones / pharmacokinetics
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Pyrrolidinones / pharmacology
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Rats
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Rats, Sprague-Dawley
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Serine Proteinase Inhibitors / chemistry*
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Serine Proteinase Inhibitors / pharmacokinetics
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Serine Proteinase Inhibitors / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Anticoagulants
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Bridged Bicyclo Compounds, Heterocyclic
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Factor Xa Inhibitors
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Pyrrolidinones
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Serine Proteinase Inhibitors