Dopaminergic activity and stereochemical considerations for rigid angular tricyclic congeners of dopamine: benzoquinoxalines and naphthothiazines.

Replacement of the oxygen atom at 1-position in the hexahydronaphthoxazines (4, PHNO) with a sulfur or nitrogen atom leads to the hexahydronaphthiazines (6, PHNT) and octahydro-benzoquinoxalines (5, POBQ) respectively and the 9-OH-PHNT shows to have a high affinity towards D-2 dopamine receptors in the binding assays; the racemic 9-OH-PHNT was then resolved and its absolute configuration was determined by CD. Inactivity on D-2 receptors of (+)-9-OCH3-PHNT 12 confirms the validity of the McDermed receptor model.