Derivatives of 4-(2-N,N-Di-n-propylaminoethyl)-5-hydroxyindole: Synthesis and Pharmacological Effects
Abstract5-Methoxy-l-methyl-4-(2-N,N-di-n-propylaminoethyl)indole (12) was synthesized from 5-hydroxyindole by a multistep synthesis. This target compound was designed as a bioisostere of “p-dimethoxy” catechol congeners of dopaminergic agonists derived from a variety of ring systems, in some of which p-dimethoxy-substituted systems are potent, active dopaminergic agonists. To complete the indole series, all possible combinations of N- and O-demethylated derivatives of 12 were prepared and were also evaluated pharmacologically. All members of this indole-derived series showed a low order of cardiovascular activity, which appeared to be independent of dopamine receptors. The lack of dopaminergic activity of 12 is cited as yet another example of the unpredictable effect of replacement of the catechol moiety of a dopaminergic agonist with a p-dimethoxy moiety.
2-Amino-4,7-dimethoxyindan derivatives: synthesis and assessment of dopaminergic and cardiovascular actions.
N-Alkylated derivatives of 2-amino-4,7-dimethoxyindan were prepared for evaluation of central and peripheral dopaminergic activity using biochemical and behavioral tests in the rat and cardiovascular responses in the cat. 2-(Di-n-propylamino)-4,7-dimethoxyindan (4e) demonstrated equal activity with apomorphine to activate peripheral presynaptic dopamine receptors. Central pre- and postsynaptic dopamine receptors were also activated with 4e. In contrast to the intense long-acting sympathomimetic actions previously reported for the 2-amino-5,8-dimethoxytetralins, these compounds produced weak, transient effects in heart rate and blood pressure. The majority of 2-amino-4,7-dimethoxyindan derivatives tested are weak or inactive pre- and postsynaptic dopamine receptor agonists.
Conversion of amines into imines by swern oxidation
Indoline (1) and 2-methylindoline (2) have been converted into indole (3) and 2-methylindole (4), and dibenzylamine (7) and phenylbenzylamine (8) have been converted into the Schiff bases (9) and (10), by Swern oxidation; the methylthiomethyl amines (5), (6), (11), and (12) were the only other products formed.