Synthesis and evaluation of acylguanidine FXa inhibitors

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4696-9. doi: 10.1016/j.bmcl.2008.07.004. Epub 2008 Jul 5.

Abstract

A series of acylguanidine derivatives were prepared and investigated as inhibitors of Factor Xa (FXa). These compounds were made by guanidine acylation with carboxylic acids using carbonyl diimidazole (CDI) as the coupling reagent. Conditions for the rapid synthesis and purification of these compounds are described along with their ability to inhibit FXa. The best FXa inhibitor is 1 with a FXa IC(50) of 6 nM.

MeSH terms

  • Anticoagulants / chemical synthesis
  • Anticoagulants / pharmacology
  • Antithrombin III / chemical synthesis*
  • Antithrombin III / pharmacology*
  • Blood Coagulation
  • Carboxylic Acids / chemistry
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Factor Xa / chemistry*
  • Guanidines / chemical synthesis*
  • Guanidines / pharmacology*
  • Guanine / chemistry
  • Humans
  • Imidazoles / chemistry
  • Inhibitory Concentration 50
  • Models, Chemical
  • Molecular Structure

Substances

  • Anticoagulants
  • Carboxylic Acids
  • Guanidines
  • Imidazoles
  • Guanine
  • Antithrombin III
  • Factor Xa