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

Bioorg Med Chem Lett. 2001 Jan 22;11(2):223-6. doi: 10.1016/s0960-894x(00)00633-8.

Abstract

The synthesis of the two enantiomers of 3-(3,4-dimethylphenyl)-1-propylpiperidine 1, a potent and selective D4 dopaminergic ligand, was performed. The 3-(3,4-dimethylphenyl)- 1-propylpiperidine with the R configuration showed an affinity for the D4 receptors 6-fold higher than the corresponding enantiomer 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 Ki ratio higher than 25,000, while the (S)-1 enantiomer was about 100-fold less selective than the (R)-1 one.

MeSH terms

  • Basal Ganglia / chemistry
  • Dopamine Agents / chemical synthesis*
  • Dopamine Agents / metabolism
  • Humans
  • Ligands
  • Molecular Conformation
  • Piperidines / chemical synthesis
  • Piperidines / metabolism*
  • Protein Binding
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D4
  • Retina / chemistry
  • Stereoisomerism

Substances

  • 3-(3,4-dimethylphenyl)-N-n-propylpiperidine
  • DRD4 protein, human
  • Dopamine Agents
  • Ligands
  • Piperidines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4