Substituted 5-amino-4,5,6,7-tetrahydroindazoles as partial ergoline structures with dopaminergic activity

J Med Chem. 1989 Oct;32(10):2388-96. doi: 10.1021/jm00130a027.

Abstract

Two series of tetrahydroindazoles were synthesized and evaluated for dopaminergic activity. A number of these partial ergoline analogues possess substituents that could mimic the C-8 substituent of the dopaminergic ergolines. Of the unsymmetrically substituted amine series 7a-k, the (monopropylamino)tetrahydroindazole 7b was most interesting as it was found to selectively activate the dopamine (DA) autoreceptor at a dose of 5 mg/kg in rats. The disubstituted amines 7g-k had significant DA postsynaptic activity as measured by increases of serum corticosterone levels in rats. The 6-substituted-5-aminotetrahydroindazoles 10a-d were found to possess only marginal dopaminergic activity.

Publication types

  • Comparative Study

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Cell Membrane / metabolism
  • Corpus Striatum / metabolism
  • Dopamine / metabolism
  • Dopamine Agents / chemical synthesis*
  • Dopamine Agents / pharmacology
  • Ergolines / chemical synthesis*
  • Ergolines / pharmacology
  • Homovanillic Acid / metabolism
  • Indazoles / chemical synthesis*
  • Indazoles / pharmacology
  • Molecular Structure
  • Prolactin / blood
  • Prolactin / metabolism
  • Pyrazoles / chemical synthesis*
  • Rats
  • Structure-Activity Relationship

Substances

  • Dopamine Agents
  • Ergolines
  • Indazoles
  • Pyrazoles
  • 3,4-Dihydroxyphenylacetic Acid
  • Prolactin
  • Dopamine
  • Homovanillic Acid