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-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.
Macchia
B
B
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Italy. bmacchia@farm.unipi.it
Cervetto
L
L
Demontis
G C
GC
Domiano
P
P
Longoni
B
B
Macchia
M
M
Minutolo
F
F
Orlandini
E
E
Ortore
G
G
Papi
C
C
D001479:Basal Ganglia / Q000737:chemistry; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D010880:Piperidines / Q000138:chemical synthesis / Q000378:metabolism*; D011485:Protein Binding; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050638:Receptors, Dopamine D4; D012160:Retina / Q000737:chemistry; D013237:Stereoisomerism
C116268:3-(3,4-dimethylphenyl)-N-n-propylpiperidine; C493599:DRD4 protein, human; D015259:Dopamine Agents; D008024:Ligands; D010880:Piperidines; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4