Synthesis and activity studies of conformationally restricted alpha-ketoamide factor Xa inhibitors

Bioorg Med Chem Lett. 2000 Jun 5;10(11):1253-6. doi: 10.1016/s0960-894x(00)00215-8.

Abstract

Conformationally restricted borolysine compounds containing a 2-(2-cyanophenylthio) benzoyl in the P3 position unexpectedly led to enhanced factor Xa inhibition. In an effort to improve both the potency and selectivity of this series by extending into the S' domain, we have replaced the boronic acid with alpha-ketoamides, utilizing a novel process that was developed in our labs.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology*
  • Factor Xa Inhibitors*
  • Models, Molecular
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amides
  • Factor Xa Inhibitors
  • Serine Proteinase Inhibitors