Halothiophene benzimidazoles as P1 surrogates of inhibitors of blood coagulation factor Xa

Bioorg Med Chem Lett. 2004 Jul 16;14(14):3763-9. doi: 10.1016/j.bmcl.2004.04.097.

Abstract

Neutral weak halothiophene benzimidazole inhibitors of the serine protease factor Xa were identified via screening of a compound library. The X-ray crystal structure of representative 3a bound to human fXa confirmed the S1 binding mode. Starting from 3a a series of halothiophene benzimidazoles was synthesized and investigated for their factor Xa inhibitory activity. This led to potent and selective achiral inhibitors against fXa such as compounds 9k and 9w.

MeSH terms

  • Antithrombins / chemical synthesis*
  • Antithrombins / pharmacology
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / pharmacology
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Design
  • Factor Xa / chemistry
  • Factor Xa Inhibitors*
  • Humans
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Trypsin / chemistry

Substances

  • Antithrombins
  • Benzimidazoles
  • Factor Xa Inhibitors
  • Serine Proteinase Inhibitors
  • benzimidazole
  • Trypsin
  • Factor Xa