Abstract
We have discovered that phenyltriazolinone is a novel and potent P1 moiety for coagulation factor Xa. X-ray structures of the inhibitors with a phenyltriazolinone in the P1 position revealed that the side chain of Asp189 has reoriented resulting in a novel S1 binding pocket which is larger in size to accommodate the phenyltriazolinone P1 substrate.
Copyright 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Anticoagulants / chemical synthesis*
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Anticoagulants / chemistry
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Anticoagulants / pharmacology
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Crystallography, X-Ray
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Drug Design*
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Factor Xa Inhibitors*
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Humans
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Isoxazoles / chemical synthesis*
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Isoxazoles / chemistry
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Isoxazoles / pharmacology
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Models, Molecular
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Molecular Structure
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Pyrazoles / chemical synthesis*
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Pyrazoles / chemistry
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Pyrazoles / pharmacology
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Pyridones / chemical synthesis*
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Pyridones / chemistry
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Pyridones / pharmacology
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Sulfones / chemical synthesis*
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Sulfones / chemistry
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Sulfones / pharmacology
Substances
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1-(3-(aminomethyl)phenyl)-N-(3-fluoro-2'-(methylsulfonyl)(1,1'-biphenyl)-4-yl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide
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Anticoagulants
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Factor Xa Inhibitors
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Isoxazoles
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Pyrazoles
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Pyridones
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Sulfones
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razaxaban
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apixaban