Pyrazole-based factor Xa inhibitors containing N-arylpiperidinyl P4 residues

Bioorg Med Chem Lett. 2007 Mar 1;17(5):1432-7. doi: 10.1016/j.bmcl.2006.11.071. Epub 2006 Dec 1.

Abstract

The synthesis, SAR, pharmacokinetic profile, and modeling studies of both monocyclic and fused pyrazoles containing substituted N-arylpiperidinyl P4 moieties that are potent and selective factor Xa inhibitors will be discussed. Fused pyrazole analog 16a, with a 2'-methylsulfonylphenyl piperidine P4 group, was shown to be the best compound in this series (FXa Ki = 0.35 nM) based on potency, selectivity, and pharmacokinetic profile.

MeSH terms

  • Animals
  • Dogs
  • Factor Xa Inhibitors*
  • Models, Molecular
  • Piperidines / administration & dosage
  • Piperidines / chemical synthesis*
  • Piperidines / pharmacokinetics*
  • Protein Binding
  • Pyrazoles / administration & dosage
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacokinetics*
  • Structure-Activity Relationship

Substances

  • Factor Xa Inhibitors
  • Piperidines
  • Pyrazoles