Abstract
Factor Xa (fXa) is a serine protease, which plays a pivotal role in the coagulation cascade. To improve the oral anticoagulant activity of fXa inhibitors containing a 1,4-diazepane moiety as the P4 part, a prodrug strategy was examined. Among the compounds evaluated in this study, amidoxime prodrugs bearing an ester moiety, such as compounds 21 and 30, showed effective oral anticoagulant activity in mice.
MeSH terms
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Administration, Oral
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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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Anticoagulants / chemical synthesis*
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Anticoagulants / chemistry
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Anticoagulants / pharmacology*
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Antithrombin III / chemical synthesis
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Antithrombin III / chemistry*
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Antithrombin III / pharmacology
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Aza Compounds / chemical synthesis
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Aza Compounds / chemistry
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Aza Compounds / pharmacology
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Blood Coagulation Tests
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Female
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Humans
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Mice
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Pregnancy
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Prodrugs / chemical synthesis*
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Prodrugs / pharmacology*
Substances
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Amidines
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Anticoagulants
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Aza Compounds
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Prodrugs
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Antithrombin III