Synthesis and characterization of selective dopamine D ₂ receptor antagonists. 2. Azaindole, benzofuran, and benzothiophene analogs of L-741,626

A series of indole, 7-azaindole, benzofuran, and benzothiophene compounds have been prepared and evaluated for affinity at D _2-like dopamine receptors. These compounds share structural elements with the classical D _2-like dopamine receptor antagonists haloperidol, N-methylspiperone and benperidol. Two new compounds, 4-(4-iodophenyl)-1-((4-methoxy-1H-indol-3-yl) methyl)piperidin-4-ol (6) and 4-(4-iodophenyl)-1-((5-methoxy-1H-indol-3-yl) methyl)piperidin-4-ol (7), were found to have high affinity to and selectivity for D ₂ versus D ₃ receptors. Changing the aromatic ring system from an indole to other heteroaromatic ring systems reduced the D ₂ binding affinity and the D ₂ versus D ₃ selectivity.