Synthesis and structure-activity relationships of novel arylalkyl 4-benzylpiperazine derivatives as sigma site selective ligands

Continuing our previous work that established that some chromones substitue d by an aryl alkyl piperazino alkyl side chain are potent and selective sig ma ligands and could be interesting in the treatment of psychosis, we synth esized 60 new compounds, replacing the chromone moiety by various cyclic sy stems. Many derivatives bind to the sigma sites in the nanomolar range and are generally selective in comparison with 5HT(1A) and the D-2 receptors. O ne of the most potent ligands of these series, 1-(2-naphthyl methyl)-4-benz yl piperazine 29, has been studied in various pharmacological tests. Althou gh it doesn't have potential in the treatment of psychosis, the results we obtained confirm the data which indicates that such derivatives could be in teresting in the treatment of inflammatory diseases. (C) 2000 Editions scie ntifiques ct medicales Elsevier SAS.