Design and synthesis of factor Xa inhibitors and their prodrugs

Bioorg Med Chem Lett. 2003 Jan 20;13(2):297-300. doi: 10.1016/s0960-894x(02)00921-6.


In addition to our previously reported fluoro acrylamides Xa inhibitors 2 and 3, a series of potent and novel cyclic diimide amidine compounds has been identified. In efforts to improve their oral bioavailability, replacement of the amidine group with methyl amidrazone gives compounds of moderate potency (14, IC(50)=0.028 microM). In the amidoxime prodrug approach, the amidoxime compounds show good oral bioavailability in rats and dogs. High plasma level of prodrug 26 and significant concentration of active drug 26a were obtained upon oral administration of prodrug 26 in rats.

MeSH terms

  • Amidines / chemical synthesis
  • Amidines / pharmacology
  • Animals
  • Biological Availability
  • Dogs
  • Drug Design
  • Factor Xa Inhibitors*
  • Prodrugs / chemical synthesis*
  • Prodrugs / pharmacology
  • Rats
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / pharmacology*
  • Structure-Activity Relationship


  • Amidines
  • Factor Xa Inhibitors
  • Prodrugs
  • Serine Proteinase Inhibitors