Synthesis and dopaminergic properties of benzo-fused analogues of quinpirole and quinelorane

In an analogy to the potent catechol dopamine D-1 agonists dihydrexidine (1) and dinapsoline (2), benzo rings were fused onto the structures of the dopamine D-2-selective agonists quinelorane (3) and quinpirole (4). Each of the phenyl ring-substituted derivatives had significant affinity for D-2 receptors, albeit somewhat lower than the two parent compounds, 3 and 4. Compounds with N-propyl and N-allyl substituents (5b, 5c, 6c, and 6d) had higher affinity for the D-2 dopamine receptor than did their corresponding secondary amines (5a and 6a). Slightly different effects on affinity of an n-propyl and an n-allyl group in the new analogues of 3 and 4 suggest that different binding orientations may be invoked at the receptor.