A novel series of hybrid compounds derived by combining 2-aminotetralin and piperazine fragments: binding activity at D2 and D3 receptors.
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.
Dutta
Aloke K
AK
Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA. adutta@wizard.pharm.wayne.edu
Fei
Xiang-Shu
XS
Reith
Maarten E A
ME
D002460:Cell Line; D065127:Dopamine D2 Receptor Antagonists; D006801:Humans; D008024:Ligands; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3; D013134:Spiperone / Q000378:metabolism; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000737:chemistry* / Q000378:metabolism
C493593:DRD3 protein, human; D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D000077489:Piperazine; C006561:2-aminotetralin; D013134:Spiperone