First structure–activity relationship study on dopamine D3 receptor agents with N-[4-(4-arylpiperazin-1-yl)butyl]arylcarboxamide structure

Structure-affinity relationships of N-[4-(4-arylpiperazin- 1-yl)butyl]arylcarboxamides as D3 receptor ligands have been well characterized but not structure-activity relationships. In a first attempt to clarify this issue, seven 1-(2,3- dichlorophenyl)piperazine derivatives and their 2-methoxyphenyl counterparts were prepared by varying the arylcarboxamide moiety. They were tested for D3 receptor binding affinities and in the Eu-GTP binding assay in order to evaluate their intrinsic activity. We have found that the intrinsic activity strongly depended on the nature of the arylcarboxamide moiety.