Design and synthesis of glycolic and mandelic acid derivatives as factor Xa inhibitors

Bioorg Med Chem Lett. 2001 Sep 3;11(17):2279-82. doi: 10.1016/s0960-894x(01)00447-4.

Abstract

A series of glycolic and mandelic acid derivatives was synthesized and investigated for their factor Xa inhibitory activity. These analogues are highly potent and selective inhibitors against fXa. In a rabbit deep vein thrombosis model, compound 26 showed significant antithrombotic effects (81% inhibition of thrombus formation) at 1.1 microM plasma concentration following intravenous administration.

MeSH terms

  • Acetanilides*
  • Amidines / chemical synthesis
  • Amidines / chemistry*
  • Amidines / pharmacology*
  • Animals
  • Biological Availability
  • Blood Coagulation Tests
  • Drug Design
  • Drug Evaluation, Preclinical / methods
  • Factor Xa Inhibitors*
  • Fibrinolysin / antagonists & inhibitors
  • Inhibitory Concentration 50
  • Injections, Intravenous
  • Mandelic Acids / chemistry*
  • Phenylacetates / chemical synthesis
  • Phenylacetates / chemistry*
  • Phenylacetates / pharmacology*
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Serine Proteinase Inhibitors / chemical synthesis
  • Serine Proteinase Inhibitors / chemistry*
  • Serine Proteinase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Venous Thrombosis / drug therapy

Substances

  • Acetanilides
  • Amidines
  • Factor Xa Inhibitors
  • Mandelic Acids
  • Phenylacetates
  • Serine Proteinase Inhibitors
  • alpha-(3-amidinylphenoxy)-2-bromo-N-(5-(pyrrolidin-1-ylcarbonyl)phenyl)phenylacetamide
  • Fibrinolysin
  • mandelic acid