Synthesis of D-oxa tricyclic partial ergolines as dopamine agonists.
A series of hetero fused hexahydro-1,4-benzoxazines has been synthesized and evaluated for dopamine agonist activity. This class of compounds is another example in which an oxygen substitution in the D ring of a partial ergoline or ergoline retains dopaminergic properties. Compound 10, trans-(+/-)-4,4a,5,6,8a,9-hexahydro-5-propyl-2H,7H-pyrazolo[4,3-g] [1,4]benzoxazine, is a D-ring analogue of trans-(+/-)-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-2H-pyrazolo[3,4-g]qu ino line (1, LY141865) and also a des-A-ring analogue of 9-oxaergoline. Compounds 10, 2-aminohexahydrothiazolo[1,4]benzoxazine 11, and 2-aminohexahydropyrimido[1,4]benzoxazine 12 possess dopaminergic activity in prolactin inhibition and 6-hydroxydopamine lesioned rat turning assays.
D000818:Animals; D018492:Dopamine Antagonists; D004873:Ergolines / Q000138:chemical synthesis* / Q000494:pharmacology; D006892:Hydroxydopamines; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D016627:Oxidopamine; D051381:Rats; D013329:Structure-Activity Relationship
D018492:Dopamine Antagonists; D004873:Ergolines; D006892:Hydroxydopamines; D016627:Oxidopamine