Structure-activity relationships of anthranilamide-based factor Xa inhibitors containing piperidinone and pyridinone P4 moieties

Bioorg Med Chem Lett. 2008 May 1;18(9):2845-9. doi: 10.1016/j.bmcl.2008.03.092. Epub 2008 Apr 8.

Abstract

Introduction of the phenyl piperidinone and phenyl pyridinone P4 moieties in the anthranilamide scaffold led to potent, selective, and orally bioavailable inhibitors of factor Xa. Anthranilamide 28 displayed comparable efficacy to apixaban in the rabbit arteriovenous-shunt (AV) thrombosis model.

MeSH terms

  • Administration, Oral
  • Animals
  • Antithrombin III* / administration & dosage
  • Antithrombin III* / chemical synthesis
  • Antithrombin III* / pharmacokinetics
  • Arteriovenous Shunt, Surgical
  • Binding Sites
  • Biological Availability
  • Models, Animal
  • Piperidines / chemistry*
  • Pyridones / chemistry*
  • Rabbits
  • Serine Proteinase Inhibitors* / administration & dosage
  • Serine Proteinase Inhibitors* / chemical synthesis
  • Serine Proteinase Inhibitors* / pharmacokinetics
  • Structure-Activity Relationship
  • Thrombosis / drug therapy*
  • Thrombosis / etiology
  • ortho-Aminobenzoates / chemistry*

Substances

  • Piperidines
  • Pyridones
  • Serine Proteinase Inhibitors
  • ortho-Aminobenzoates
  • Antithrombin III
  • anthranilamide