N-arylalkylpiperidines as high-affinity sigma-1 and sigma-2 receptor ligands: phenylpropylamines as potential leads for selective sigma-2 agents

Dean Y Maeda; Wanda Williams; Wes E Kim; Linn N Thatcher; Wayne D Bowen; Andrew Coop

doi:10.1016/s0960-894x(01)00788-0

N-arylalkylpiperidines as high-affinity sigma-1 and sigma-2 receptor ligands: phenylpropylamines as potential leads for selective sigma-2 agents

Bioorg Med Chem Lett. 2002 Feb 11;12(3):497-500. doi: 10.1016/s0960-894x(01)00788-0.

Authors

Dean Y Maeda¹, Wanda Williams, Wes E Kim, Linn N Thatcher, Wayne D Bowen, Andrew Coop

Affiliation

¹ Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 North Pine Street, Baltimore, MD 21201, USA.

PMID: 11814827
DOI: 10.1016/s0960-894x(01)00788-0

Abstract

To delineate the differences between the structural requirements necessary for recognition at sigma-1 and sigma-2 receptors, a range of phenethyl- and phenylpropylpiperidines were evaluated in binding assays. Phenethylpiperidines were found to favor sigma-1 receptors, whereas phenylpropylpiperidines tend to favor sigma-2 receptors. It appears that phenylpropylamine is a potential pharmacophore for selective sigma-2 ligands.

MeSH terms

Antipsychotic Agents / chemical synthesis
Binding, Competitive / drug effects
Ligands
Piperidines / chemical synthesis*
Piperidines / pharmacology*
Propylamines / chemistry*
Pyridines / chemical synthesis*
Pyridines / pharmacology*
Receptors, sigma / drug effects*
Sigma-1 Receptor
Structure-Activity Relationship

Substances

Antipsychotic Agents
Ligands
Piperidines
Propylamines
Pyridines
Receptors, sigma
sigma-2 receptor