Abstract
A variety of P4 motifs have been examined to increase the binding affinity and in vitro anticoagulant potency of our biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamide-based fXa inhibitors. Highly potent 2-naphthyl-P1 fXa inhibitors (K(i)< or =2 nM) with improved in vitro anticoagulant activity (2xTG< or =1 microM) and respectable pharmacokinetic properties have been discovered.
MeSH terms
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Amides / chemistry*
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Amides / metabolism
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Amides / pharmacology
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Animals
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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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Factor Xa Inhibitors*
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Humans
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Protein Binding
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Pyrazoles / chemistry*
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Pyrazoles / metabolism
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Pyrazoles / pharmacology
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Rats
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Rats, Sprague-Dawley
Substances
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Amides
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Factor Xa Inhibitors
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Pyrazoles
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pyrazole
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Antithrombin III