Synthesis and dopaminergic properties of the two enantiomers of 3-(3,4-dimethylphenyl)-1-propylpiperidine, a potent and selective dopamine D4 receptor ligand

The synthesis of the two enantiomers of 3-(3,4-dimethylphenyl)-1-propylpipe ridine 1, a potent and selective D4 dopaminergic ligand, was performed. The 3-(3,4-dimethylpheny1)-l-propylpiperidine with the R configuration showed an affinity for the D4 receptors 6-fold higher than the corresponding enant iomer with the S configuration. Furthermore, the (R)-1 enantiomer proved to be highly selective for D4 receptors with respect to D2-D3 receptors, with a K-i ratio higher than 25,000, while the (S)-1 enantiomer was about 100-f old less selective than the (R)-1 one (C) 2001 Elsevier Science Ltd. All ri ghts reserved.