Dopamine autoreceptor agonists: resolution and pharmacological activity of 2,6-diaminotetrahydrobenzothiazole and an aminothiazole analogue of apomorphine.

The enantiomers of the aminothiazole analogues of the known dopaminergic agonists apomorphine (1) and 2-aminohydroxytetralin (2) have been prepared. The absolute configurations of the enantiomers of 2,6-diaminotetrahydrobenzothiazole have been established by X-ray crystallographic analysis. Dopamine (DA) autoreceptor agonist activities of the compounds were evaluated. Testing revealed (-)-5, the S enantiomer, to be the most active compound tested (inhibition of GBL accelerated dopamine synthesis and inhibition of alpha-methyltyrosine-induced decline of DA). In addition (-)-5 does not exhibit stereotyped behavior, suggesting a pronounced selectivity for DA autoreceptors.