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.
D000818:Animals; D052160:Benzothiazoles; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D000077487:Pramipexole; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D052160:Benzothiazoles; D007202:Indicators and Reagents; D011804:Quinolines; D011954:Receptors, Dopamine; D013844:Thiazoles; C051622:9-amino-6-methyl-5,6,6a,7-tetrahydro-4H-benzo-(de)thiazolo(4,5-g)quinoline; D000077487:Pramipexole; D004298:Dopamine