Assessment of a potential dopaminergic prodrug moiety in several ring systems.

J G Cannon, D C Furlano, R G Dushin, Y A Chang, S R Baird, L N Soliman, J R Flynn, J P Long, R K Bhatnagar

Index: J. Med. Chem. 29(10) , 2016-20, (1986)

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Abstract

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.