Synthesis and activities of oxidative metabolites of the anti-arthritic drug candidate S-2474

Bioorg Med Chem. 2003 May 29;11(11):2415-9. doi: 10.1016/s0968-0896(03)00141-x.

Abstract

We have synthesized and characterized some oxidative metabolites of S-2474. In this study, we discovered a novel skeleton, the 2,3-dihydrobenzofuran derivative, which inhibited PGE(2) production at a very low concentration and was effective in the anti-carrageenin footpad edema assay.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology
  • Benzofurans / chemical synthesis*
  • Benzofurans / pharmacology
  • Cyclic S-Oxides / chemistry*
  • Cyclic S-Oxides / metabolism
  • Cyclic S-Oxides / pharmacology
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / biosynthesis
  • Edema / drug therapy
  • Edema / metabolism
  • Humans
  • Interleukin-1 / metabolism
  • Leukotriene B4 / metabolism
  • Lipoxygenase Inhibitors*
  • Microsomes, Liver / metabolism
  • Rats
  • Thiazoles / chemistry*
  • Thiazoles / metabolism
  • Thiazoles / pharmacology

Substances

  • ((E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)- 2-ethyl-1,2-isothiazolidine-1,1-dioxide)
  • Anti-Inflammatory Agents
  • Benzofurans
  • Cyclic S-Oxides
  • Interleukin-1
  • Lipoxygenase Inhibitors
  • Thiazoles
  • Leukotriene B4
  • Dinoprostone