Abstract
A series of 7-hydroxy-2-[N-alkyl-(N-(4-phenylpiperazine)-alkyl)amino]tetralins was developed based on a novel hybrid approach that combined 2-aminotetralin and arylpiperazine pharmacophoric moieties. Our preliminary study revealed that a four-methylene butyl linker produced very potent compounds for both the D2 and D3 receptors. Further structure-activity studies led to a novel template showing 50- to 100-fold selectivity for the D3 receptor.
MeSH terms
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Cell Line
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Dopamine D2 Receptor Antagonists*
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Humans
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Ligands
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Piperazine
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Piperazines / chemistry*
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Piperazines / metabolism
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Protein Binding
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Radioligand Assay
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Receptors, Dopamine D2 / metabolism
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Receptors, Dopamine D3
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Spiperone / metabolism
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Structure-Activity Relationship
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Tetrahydronaphthalenes / chemistry*
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Tetrahydronaphthalenes / metabolism
Substances
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DRD3 protein, human
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Dopamine D2 Receptor Antagonists
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Ligands
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Piperazines
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Receptors, Dopamine D2
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Receptors, Dopamine D3
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Tetrahydronaphthalenes
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Piperazine
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2-aminotetralin
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Spiperone