High-affinity and selective dopamine D₃ receptor full agonists.

We have designed, synthesized and evaluated a series of new compounds with the goal to identify potent and selective D(3) ligands. The two most potent and selective new D(3) ligands are compounds 38 and 52, which bind to the D(3) receptors with a K(i) value of <nM and display a selectivity of 450-494 times over the D(2) receptors and >10,000 times over the D(1) receptors. Both 38 and 52 are full agonists with high potency at the D(3) receptor in a D(3) functional assay.