Assessment of a potential dopaminergic prodrug moiety in several ring systems.
The ortho hydroxy/methyl, hydroxy/hydroxymethyl, hydroxy/formyl, and hydroxy/carboxy substitution patterns, some of which confer dopaminergic agonist effects upon 2-aminotetralin ring systems, have been incorporated into beta-phenethylamine, 2-aminoindan, and trans-octahydrobenzo[f]quinoline rings. Certain of the 2-aminoindan derivatives displayed pharmacologic properties consistent with their being dopaminergic agonists. The beta-phenethylamine derivative did not show any significant dopamine-like activity. The 7-hydroxy-8-methyloctahydrobenzo[f]quinoline derivative 4a was a moderately potent, short-acting DA2 receptor antagonist. All of the carboxylic acid derivatives were inert. Of the ortho hydroxy/methyl derivatives, only the 5-hydroxy-6-methyl-2-aminotetralin derivative displayed pharmacological properties consistent with its being a dopaminergic prodrug. It is concluded that 5-hydroxy-6-methyl-2-(di-n-propylamino)tetralin (1a) is structurally unique for a dopaminergic drug.
D000818:Animals; D002415:Cats; D007189:Indans / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D007189:Indans; D007192:Indenes; D009281:Naphthalenes; D010627:Phenethylamines; D011804:Quinolines; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; C006545:2-aminoindan; C006561:2-aminotetralin; C039108:benzo(f)quinoline