Synthesis of 4-substituted 2H-naphth[1,2-b]-1,4-oxazines, a new class of dopamine agonists.
A series of tricyclic oxazines, namely, the 4-substituted 2H-naphth[1,2-b]-1,4-oxazines, have been synthesized and assayed for dopamine agonist activity. One of the members of this series, compound (+)VII-15, was found to be a remarkably potent agonist in vivo when tested in the standard 6-hydroxydopamine lesioned rat assay. The absolute configuration of the compound corresponds to that found in the active isomer of apomorphine. Its activity at the alpha 2 receptor (vs. [3H]clonidine) is relatively low. It also failed to stimulate the synthesis of cAMP in the carp retina assay, thus giving the compound a highly selective profile in favor of the D2 receptor.
D000818:Animals; D001058:Apomorphine / Q000378:metabolism; D002417:Cattle; D002540:Cerebral Cortex / Q000378:metabolism; D003000:Clonidine / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives*; D006892:Hydroxydopamines / Q000494:pharmacology; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D009043:Motor Activity / Q000187:drug effects; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D016627:Oxidopamine; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D012399:Rotation; D013329:Structure-Activity Relationship
D006892:Hydroxydopamines; D007202:Indicators and Reagents; D010078:Oxazines; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D016627:Oxidopamine; D003000:Clonidine; D001058:Apomorphine; D004298:Dopamine