N,N-Dialkylated 4-(4-arylsulfonylpiperazine-1-carbonyl)-benzamidines and 4-((4-arylsulfonyl)-2-oxo-piperazin-1-ylmethyl)-benzamidines as Potent Factor Xa Inhibitors

Bioorg Med Chem Lett. 2004 May 3;14(9):2073-8. doi: 10.1016/j.bmcl.2004.02.049.


A class of N,N-dialkylated 4-(4-arylsulfonylpiperazine-1-carbonyl)-benzamidines and 4-((4-arylsulfonyl)-2-oxo-piperazin-1-ylmethyl)-benzamidines has been discovered as potent factor Xa inhibitors with desirable in vitro and in vivo anticoagulant activity, but with low oral bioavailability. The 5-chloroindole and 6-chlorobenzo[b]thiophene groups are optimal as the factor Xa S1 binding elements. The strategy of incorporating a side chain on the piperazine nucleus to enhance binding affinity has been examined.

MeSH terms

  • Benzamidines / chemistry
  • Benzamidines / pharmacokinetics
  • Benzamidines / pharmacology*
  • Biological Availability
  • Factor Xa Inhibitors*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacokinetics
  • Serine Proteinase Inhibitors / pharmacology*


  • Benzamidines
  • Factor Xa Inhibitors
  • Serine Proteinase Inhibitors