Discovery of selective dopamine D3 ligands: II. 2-[4-[3-(4-aryl-1-piperazinyl)propoxy]phenyl]benzimidazole partial agonists

A novel series of 2-[4-[3-(4-aryl-1-piperazinyl)propoxy]phenyl]benzimidazole dopamine D3 receptor agonists has been discovered. The aryl group was crucial for activity and Topliss analysis confirmed that phenyl was optimal for DA D3 receptor binding and selectivity. The phenyl analogue 3 was a partial agonist in a second messenger assay. It increased DA synthesis in rat brain and inhibited exploratory locomotor activity in rodents.