Synthesis of 4-substituted 2H-naphth[1,2-b]-1,4-oxazines, a new class of dopamine agonists

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Abstract
A series of tricyclic oxazines, i.e., the 4-substituted 2H-naphth[1,2-b]-1,4-oxazines, were synthesized and assayed for dopamine agonist activity. One of the members of this series, compound (+) VII-15 [(+)-trans-3,4,4a,5,6,10b-hexahydro-4-propyl-2H-naphth[1,2-b]-1,4-oxazin-9-ol], was a remarkably potent agonist in vivo when tested in the standard 6-hydroxydopamine lesioned rat assay. The absolute configuration of the compound corresponded to that found in the active isomer of apomorphine. Its activity at the .alpha.2 receptor (vs. [3H]clonidine) was 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.