N-n-Propyl-substituted 3-(dimethylphenyl)piperidines display novel discriminative properties between dopamine receptor subtypes: synthesis and receptor binding studies.

doi:10.1021/JM9708700

Paper

N-n-Propyl-substituted 3-(dimethylphenyl)piperidines display novel discriminative properties between dopamine receptor subtypes: synthesis and receptor binding studies.

Published Nov 13, 1998 · L. Cervetto, G. Demontis, G. Giannaccini

Journal of medicinal chemistry

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7

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Abstract

3-Phenylpiperidines (PPEs) have been thoroughly investigated in view of their interesting dopaminergic activity, and the N-n-propyl substitution has been suggested as the most effective among several PPEs differently substituted on the phenyl ring. In previous studies, we found that the dimethyl substitution on the phenyl ring of N-unsubstituted PPEs provided compounds active toward alpha2-adrenergic receptors (alpha2-ARs), which proved to possess interesting selectivity properties. The high degree of homology between the binding domains of alpha2-ARs and D4-dopaminergic receptors (D4-DARs) prompted us to verify whether this kind of substitution on the aromatic ring might prove to be active against retinal DARs of the D4 subtype. On the basis of these premises, we synthesized the dimethylphenyl-substituted PPEs 4a-f, in which an n-propyl chain is present on the aminic nitrogen. Radioligand binding assays on bovine retina and striatum membranes for D1-like and D2-like DARs indicated that PPEs 4a, 4b, and 4f possess a high affinity and selectivity for the D4-DAR subtype of bovine retina.

In Vitro Study

Study Snapshot

N-n-propyl-substituted 3-(dimethylphenyl)piperidines show high affinity and selectivity for the D4-dopaminergic receptor subtype in bovine retina.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

N-n-Propyl-substituted 3-(dimethylphenyl)piperidines display novel discriminative properties between dopamine receptor subtypes: synthesis and receptor binding studies.

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References

Citations

Stereoselective synthesis of (-)-3-PPP through palladium-catalysed unactivated C(sp3)-H arylation at the C-3 position of l-pipecolinic acid

This study presents a highly efficient route for the stereoselective synthesis of (-)-3-PPP (preclamol) using palladium-catalyzed C(sp3)-H arylation and radical decarboxylation reactions, with nitrogen substitution affecting the reaction efficiency.

Synthesis of substituted 3-arylpiperidines and 3-arylpyrrolidines by radical 1,4 and 1,2-aryl migrations

Substituted 3-arylpiperidines and 3-arylpyrrolidines can be synthesized using radical 1,4- and 1,2-aryl migrations, with various starting materials.

Pathogenesis of degenerative retinopathies induced by thioridazine and other antipsychotics: a dopamine hypothesis

Thioridazine and other antipsychotics cause degenerative retinopathies by blocking retinal D2/D4 receptors, potentially affecting retinal function and affecting drug safety.

New synthesis of 3-aryl-N-n-propyl-piperidines

This study presents a new six-step synthesis of 3-aryl-N-n-propyl-piperidines, offering useful building blocks for heterocyclic chemistry.

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

The R-configuration of 3-(3,4-dimethylphenyl)-1-propylpiperidine is highly selective for D4 receptors, with a K i ratio of over 25,000, while the S-configuration is 100-fold less selective.