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

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.