Abstract
Compound 1 was identified by high throughput screening as a novel, potent, non-amidine factor Xa inhibitor with good selectivity against thrombin and trypsin. A series of modifications of the three aromatic groups of 1 was investigated. Substitution of chlorine or bromine for fluorine on the aniline ring led to the discovery of subnanomolar factor Xa inhibitors. Positions on the anthranilic acid ring that can accommodate further substitution were also identified.
MeSH terms
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Animals
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Anticoagulants / chemical synthesis
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Anticoagulants / pharmacology
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Cattle
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Factor Xa Inhibitors*
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Heterocyclic Compounds / pharmacology
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Humans
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Indicators and Reagents
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Kinetics
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Prothrombin Time
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Serine Proteinase Inhibitors / pharmacology
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Structure-Activity Relationship
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Thiophenes / chemistry
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Thiophenes / pharmacology*
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Thrombin / antagonists & inhibitors
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Trypsin Inhibitors / chemical synthesis
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Trypsin Inhibitors / pharmacology
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ortho-Aminobenzoates / chemistry
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ortho-Aminobenzoates / pharmacology*
Substances
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Anticoagulants
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Factor Xa Inhibitors
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Heterocyclic Compounds
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Indicators and Reagents
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Serine Proteinase Inhibitors
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Thiophenes
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Trypsin Inhibitors
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ortho-Aminobenzoates
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Thrombin