Synthesis and biological activity of some known and putative duloxetine metabolites

Bioorg Med Chem Lett. 2004 Jul 5;14(13):3481-6. doi: 10.1016/j.bmcl.2004.04.066.

Abstract

Several putative phase I duloxetine metabolites, 4-hydroxy-, 5-hydroxy-, 6-hydroxy-, 5-hydroxy-6-methoxy-, 6-hydroxy-5-methoxy-, 5,6-dihydroxy-, and 4,6-dihydroxyduloxetine were synthesized, and their phase II metabolite as glucuronide or sulfate conjugates were also synthesized. Their in vitro binding activities were compared to that of parent compound duloxetine.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic Uptake Inhibitors / chemical synthesis*
  • Adrenergic Uptake Inhibitors / metabolism
  • Adrenergic Uptake Inhibitors / pharmacology
  • Binding Sites
  • Cloning, Molecular
  • Dopamine Plasma Membrane Transport Proteins
  • Duloxetine Hydrochloride
  • Glucuronides / metabolism
  • Humans
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins / metabolism
  • Models, Chemical
  • Nerve Tissue Proteins / metabolism
  • Radioligand Assay
  • Sulfates / metabolism
  • Thiophenes / chemical synthesis*
  • Thiophenes / metabolism
  • Thiophenes / pharmacology

Substances

  • Adrenergic Uptake Inhibitors
  • Dopamine Plasma Membrane Transport Proteins
  • Glucuronides
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Sulfates
  • Thiophenes
  • Duloxetine Hydrochloride