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 D2, D 3, and D4 receptors were determined. Two of these compounds, 14a and 14b, displayed high binding affinity at D3 (K i = 0.18 and 0.4 nM, respectively), and selectivity for D 3vs. D2 receptors (87-fold and 60-fold, respectively). These two compounds had low binding affinity at D4 receptors and σ receptor sites. The intrinsic activity of these compounds at D 2 and D3 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.
|Number of pages||7|
|State||Published - Sep 2013|