Abstract
Previously, we identified cyclohexane diamine derivative 1 as orally bioavailable factor Xa inhibitor. We have investigated two racemic cis-piperidine diamine derivatives 2 and 3 based on 1. Compounds 2a-e showed higher fXa inhibitory activity, anticoagulant activity, and aqueous solubility than 3a-e having same substituent. Compounds 2a, 2c, 2e, and 2g-m having sp2 nitrogen, especially amide and urea derivatives, showed potent anticoagulant activity. Compounds 2h and 2k showed high oral activities in rats.
MeSH terms
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Administration, Oral
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Animals
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Area Under Curve
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Diamines / chemistry
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Drug Design
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Factor Xa Inhibitors*
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Haplorhini
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Humans
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Microsomes, Liver / metabolism
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Piperidines / administration & dosage
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Piperidines / chemical synthesis
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Piperidines / chemistry*
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Piperidines / pharmacology*
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Rats
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Serine Proteinase Inhibitors / administration & dosage
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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*
Substances
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Diamines
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Factor Xa Inhibitors
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Piperidines
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Serine Proteinase Inhibitors