Monophenolic 2-(dipropylamino)indans and related compounds: central dopamine-receptor stimulating activity

Abstract

Monophenolic 2-(dipropylamino)indans and related compounds were synthesized and tested for central dopamine-receptor stimulating activity, using biochemical and behavioral tests in rats and emesis tests in dogs. The active compounds possess similar relative potencies in eliciting the 3 different dopamine-receptor mediated effects measured. 4-Hydroxy-2-(dipropylamino)indan was the most potent of the new compounds. The corresponding 5-hydroxy analog was less active. 4-Hydroxy-2-[(dipropylamino)methyl]indan is a new type of dopaminergic agent with a phenylpropylamine moiety in its framework instead of the phenylethylamine structure, common to most dopamine-receptor agonists. This compound was 10-20 times less active than apomorphine. 6,7,8,9-Tetrahydro-1-hydroxy-N,N-dipropyl-5H-6-benzocycloheptenylamine and 5-hydroxy-2-[(dipropylamino)methyl]tetralin were both inactive. As the intramolecular distances between functional groups in the indans studied are different from those in, e.g., apomorphine, apparently a certain variation of the distances can be accepted by the receptor. The position of the OH group on the aromatic ring is important for the activity, and emetic activity may be associated with dopaminergic agonists of the indan and of the tetralin type of structure.