Abstract
A neutral inhibitor of the serine protease factor Xa was identified via a high-throughput screen of a commercial library. The initial lead 1 demonstrated reversible and competitive inhibition kinetics for factor Xa and possessed a high degree of selectivity versus other related serine proteases. Initial modeling efforts and the generation of a series of analogues of 1 are described.
MeSH terms
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Aniline Compounds / chemistry
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Aniline Compounds / isolation & purification
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Aniline Compounds / pharmacology*
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Antithrombin III / chemical synthesis
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Antithrombin III / chemistry
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Antithrombin III / metabolism*
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Antithrombin III / pharmacology*
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Catalytic Domain / physiology
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Drug Evaluation, Preclinical
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Fibrinolysin / drug effects
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Humans
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Mass Screening
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Models, Molecular*
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Monte Carlo Method
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Protein Conformation
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Structure-Activity Relationship
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Thiophenes / chemistry
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Thiophenes / isolation & purification
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Thiophenes / pharmacology*
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Thrombin / drug effects*
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Trypsin / drug effects
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Urokinase-Type Plasminogen Activator / drug effects*
Substances
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Aniline Compounds
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Thiophenes
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Antithrombin III
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Trypsin
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Thrombin
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Fibrinolysin
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Urokinase-Type Plasminogen Activator