Synthesis and dopamine antagonist activity of 2-thioether derivatives of the ergoline ring system

J Med Chem. 1993 Apr 2;36(7):912-8. doi: 10.1021/jm00059a017.

Abstract

A series of 2-thioether derivatives of a number of clavine alkaloid (ergoline) ring systems have been synthesized and tested for dopamine antagonist activity. Of the compounds tested 2-(methylthio)-agroclavine (8,9-didehydro-6,8-dimethyl-2-(methylthio)ergoline) (6) was the most potent and had a profile of activity in animal models indicative of potential antipsychotic activity. The synthesis and biological activity of a number of metabolites of 6, including the 13-hydroxy derivative, are also reported.

MeSH terms

  • Animals
  • Antipsychotic Agents / chemical synthesis*
  • Antipsychotic Agents / pharmacology
  • Behavior, Animal / drug effects
  • Dogs
  • Dopamine Antagonists*
  • Ergolines / chemical synthesis*
  • Ergolines / pharmacology
  • Female
  • Male
  • Mice
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Structure-Activity Relationship
  • Sulfides / chemical synthesis*
  • Sulfides / pharmacology

Substances

  • Antipsychotic Agents
  • Dopamine Antagonists
  • Ergolines
  • Sulfides