Bivalent ligand approach on 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine: Synthesis and binding affinities for 5-HT7 and 5-HT1A receptors

We here report on the synthesis and binding properties at 5-HT7 and 5-HT1A receptors of ligands 3–12, that were designed according to the ‘bivalent ligand’ approach. Two moieties of the 5-HT7/5-HT1A ligand 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine (1) were linked through their 3-methoxy substituent by polymethylene chains of variable length, with the aim to increase the affinity for 5-HT7 receptor and the selectivity over 5-HT1A receptors. In the best cases, the dimers showed affinities for 5-HT7 receptors as high as the monomer with no improvement in selectivity. Some dimers displayed 5-HT1A receptor affinities slightly higher than monomer 1.

Figure optionsDownload as PowerPoint slide