Abstract
A series of substituted 1H-indolyl carboxylic acid amides that contain a N-(2-methoxyphenyl)piperazine or N-(2-fluoroethoxy)piperazine group were synthesized and their affinities for human dopamine D(2), D(3), and D(4) receptors were determined. Two of these compounds, 14a and 14b, displayed high binding affinity at D(3) (K(i) = 0.18 and 0.4 nM, respectively), and selectivity for D(3)vs. D(2) receptors (87-fold and 60-fold, respectively). These two compounds had low binding affinity at D(4) receptors and σ receptor sites. The intrinsic activity of these compounds at D(2) and D(3) receptors was determined using a forskolin-dependent adenylyl cyclase inhibition assay; both 14a and 14b were found to be partial agonists. Furthermore, for compound 14a, the log D value of 2.85 suggested it has suitable lipophilicity for crossing the blood-brain-barrier.