Synthesis and antirheumatic activity of the metabolites of esonarimod

Bioorg Med Chem. 2002 Aug;10(8):2713-21. doi: 10.1016/s0968-0896(02)00084-6.

Abstract

We have developed esonarimod, (+/-)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid, as a new antirheumatic drug. Now we describe herein the preparation of the enantiomers of (+/-)-deacetylesonarimod, the pharmaceutically active metabolites of esonarimod, and comparison of their antirheumatic activities. No significant difference has been observed between the two enantiomers. In a pre-clinical study of esonarimod, other metabolites were detected in rat blood or urine. We also synthesized these compounds as authentic samples to analyze the human metabolites in clinical studies of esonarimod.

MeSH terms

  • Animals
  • Antirheumatic Agents / blood
  • Antirheumatic Agents / chemical synthesis*
  • Antirheumatic Agents / metabolism*
  • Antirheumatic Agents / urine
  • Humans
  • Ketones
  • Phenylpropionates / chemical synthesis
  • Phenylpropionates / metabolism
  • Rats
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfides

Substances

  • Antirheumatic Agents
  • Ketones
  • Phenylpropionates
  • Sulfides
  • esonarimod