Synthesis, structure and quantitative structure-activity relationships of σ receptor ligands, 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazines

Article abstract of DOI:10.1016/S0968-0896(97)00093-X

A set of the title compounds having different substituents (R₁, R₂) on their phenyl groups was synthesized to find σ receptor binding affinity. Among the compounds, 2b (R₁=R₂=Cl) has the most potent σ₁-binding activity, while 2a (R₁=R₂=H, SA4503) was most selective to σ₁ over σ₂ receptor. The crystal structures of 2a and 2b were shown, by X-ray crystallography, to be similar except for the one torsional angle of their propylene parts. Quantitative structure-activity relationship study suggested the affinity of the compounds to the σ₁ receptor was dependent on the electronic feature, Swain-Lupton's R or S(π) that was derived by molecular orbital method, of R₁ and R₂.