Novel factor Xa inhibitors based on a benzoic acid scaffold and incorporating a neutral P1 ligand

Bioorg Med Chem Lett. 2004 Jun 7;14(11):2801-5. doi: 10.1016/j.bmcl.2004.03.059.

Abstract

A series of novel, highly potent, achiral factor Xa inhibitors based on a benzoic acid scaffold and containing a chlorophenethyl moiety directed towards the protease S1 pocket is described. A number of structural features, such as the requirements of the P1, P4 and ester-binding pocket ligands were explored with respect to inhibition of factor Xa. Compound 46 was found to be the most potent compound in a series of antithrombotic secondary assays.

MeSH terms

  • Benzoates / chemical synthesis
  • Benzoates / pharmacology*
  • Blood Coagulation Tests
  • Drug Stability
  • Factor Xa Inhibitors*
  • Fibrinolytic Agents / chemical synthesis*
  • Fibrinolytic Agents / pharmacology
  • Humans
  • Ligands
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / pharmacology
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Benzoates
  • Factor Xa Inhibitors
  • Fibrinolytic Agents
  • Ligands
  • Protease Inhibitors