Bivalent ligand approach on 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine: synthesis and binding affinities for 5-HT(7) and 5-HT(1A) receptors

Bioorg Med Chem. 2007 Aug 1;15(15):5316-21. doi: 10.1016/j.bmc.2007.05.010. Epub 2007 May 6.

Abstract

We here report on the synthesis and binding properties at 5-HT(7) and 5-HT(1A) receptors of ligands 3-12, that were designed according to the 'bivalent ligand' approach. Two moieties of the 5-HT(7)/5-HT(1A) 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-HT(7) receptor and the selectivity over 5-HT(1A) receptors. In the best cases, the dimers showed affinities for 5-HT(7) receptors as high as the monomer with no improvement in selectivity. Some dimers displayed 5-HT(1A) receptor affinities slightly higher than monomer 1.

MeSH terms

  • Animals
  • Cell Line
  • Humans
  • Ligands
  • Molecular Structure
  • Piperazines / chemistry*
  • Protein Binding
  • Rats
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Receptors, Serotonin / metabolism*
  • Structure-Activity Relationship

Substances

  • 4-(2-(3-methoxyphenyl)ethyl)-1-(2-methoxyphenyl)piperazine
  • 5-HT(7) receptor, rat
  • Ligands
  • Piperazines
  • Receptors, Serotonin
  • Receptor, Serotonin, 5-HT1A