Phenyltriazolinones as potent factor Xa inhibitors

Bioorg Med Chem Lett. 2010 Feb 15;20(4):1373-7. doi: 10.1016/j.bmcl.2010.01.011. Epub 2010 Jan 11.

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.

MeSH terms

  • Anticoagulants / chemical synthesis*
  • Anticoagulants / chemistry
  • Anticoagulants / pharmacology
  • Crystallography, X-Ray
  • Drug Design*
  • Factor Xa Inhibitors*
  • Humans
  • Isoxazoles / chemical synthesis*
  • Isoxazoles / chemistry
  • Isoxazoles / pharmacology
  • Models, Molecular
  • Molecular Structure
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology
  • Pyridones / chemical synthesis*
  • Pyridones / chemistry
  • Pyridones / pharmacology
  • Sulfones / chemical synthesis*
  • Sulfones / chemistry
  • Sulfones / pharmacology

Substances

  • 1-(3-(aminomethyl)phenyl)-N-(3-fluoro-2'-(methylsulfonyl)(1,1'-biphenyl)-4-yl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide
  • Anticoagulants
  • Factor Xa Inhibitors
  • Isoxazoles
  • Pyrazoles
  • Pyridones
  • Sulfones
  • razaxaban
  • apixaban