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Novel analogs of l-prolyl-l-leucylglycinamide (PLG) were synthesized wherein the prolyl residue was replaced with other amino acids based on a 3,5-disubstituted proline scaffold. In some examples, the l-leucyl residue was also replaced by l-valine. These analogs were tested for their ability to enhance the binding of [ 3 H]-N-propylnorapomorphine to short isoform of human dopamine D 2 receptors.Compounds 18b and 19b, increased [ 3 H] NPA binding at concentrations between 10 −12 and 10 −9 M, which is similar to the effect of PLG in this assay and, provides evidences that these compounds are acting as allosteric modulators of dopamine D 2 receptors.
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