Abstract
A series of glycolic and mandelic acid derivatives was synthesized and investigated for their factor Xa inhibitory activity. These analogues are highly potent and selective inhibitors against fXa. In a rabbit deep vein thrombosis model, compound 26 showed significant antithrombotic effects (81% inhibition of thrombus formation) at 1.1 microM plasma concentration following intravenous administration.
MeSH terms
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Acetanilides*
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Amidines / chemical synthesis
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Amidines / chemistry*
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Amidines / pharmacology*
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Animals
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Biological Availability
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Blood Coagulation Tests
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Drug Design
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Drug Evaluation, Preclinical / methods
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Factor Xa Inhibitors*
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Fibrinolysin / antagonists & inhibitors
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Inhibitory Concentration 50
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Injections, Intravenous
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Mandelic Acids / chemistry*
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Phenylacetates / chemical synthesis
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Phenylacetates / chemistry*
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Phenylacetates / pharmacology*
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Rabbits
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Rats
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Rats, Sprague-Dawley
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Serine Proteinase Inhibitors / chemical synthesis
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Serine Proteinase Inhibitors / chemistry*
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Serine Proteinase Inhibitors / pharmacology*
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Structure-Activity Relationship
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Venous Thrombosis / drug therapy
Substances
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Acetanilides
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Amidines
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Factor Xa Inhibitors
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Mandelic Acids
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Phenylacetates
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Serine Proteinase Inhibitors
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alpha-(3-amidinylphenoxy)-2-bromo-N-(5-(pyrrolidin-1-ylcarbonyl)phenyl)phenylacetamide
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Fibrinolysin
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mandelic acid