Abstract
We have recently discovered imidazo[1,5-c]imidazol-3-one derivative 1 as a potent, selective, and orally bioavailable factor Xa (FXa) inhibitor. In this study, we have synthesized metabolites of 1 and evaluated their biological activities. As a result, we identified the active metabolites S-5 and 6 with a potent FXa inhibitory activity comparable to 1 and a favorable pharmacokinetic profile in monkeys.
MeSH terms
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Animals
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Anticoagulants / blood
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Anticoagulants / chemical synthesis*
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Anticoagulants / chemistry
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Anticoagulants / pharmacokinetics
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Area Under Curve
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Factor Xa / physiology*
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Factor Xa Inhibitors
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Humans
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Imidazoles / blood
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Imidazoles / chemical synthesis*
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Imidazoles / chemistry
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Imidazoles / pharmacokinetics
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Macaca fascicularis
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Piperidines / blood
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Piperidines / chemical synthesis*
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Piperidines / chemistry
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Piperidines / pharmacokinetics
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Spectrophotometry, Infrared
Substances
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Anticoagulants
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Factor Xa Inhibitors
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Imidazoles
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Piperidines
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Factor Xa