Synthesis of (7R)-7H-indolo[3,4-gh][1,4]benzoxazines, a new class of D-heteroergolines with dopamine agonist activity.
Synthesis of several members of the 9-oxaergoline ring system is presented. Both the C/D cis and the C/D trans isomers of 4,6,6a,8,9,10a-hexahydro-7-ethyl-7H-indolo[3,4-gh] [1,4]benzoxazine were prepared, and the C/D trans isomer was resolved into its optical isomers. The enantiomer having the highest affinity for the [3H]apomorphine binding site, (-)-trans-6-ethyl-9-oxaergoline [(-)-6b], was shown to have the same absolute configuration as the natural ergolines, namely, 6aR, 10aR. In vivo and in vitro pharmacological evaluation shows these 9-oxaergolines to possess potent dopamine agonist properties.
D000818:Animals; D001058:Apomorphine / Q000378:metabolism; D002417:Cattle; D002540:Cerebral Cortex / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004298:Dopamine / Q000378:metabolism*; D007536:Isomerism; D010078:Oxazines / Q000138:chemical synthesis* / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism
D010078:Oxazines; D011942:Receptors, Adrenergic, alpha; D001058:Apomorphine; D004298:Dopamine