Design and synthesis of new benzimidazole-arylpiperazine derivatives acting as mixed 5-HT1A/5-HT3 ligands

Bioorg Med Chem Lett. 2003 Oct 6;13(19):3177-80. doi: 10.1016/s0960-894x(03)00706-6.

Abstract

A series of new benzimidazole-arylpiperazine derivatives III were designed, synthesized and evaluated for binding affinity at serotoninergic 5-HT(1A) and 5-HT(3) receptors. Compound IIIc was identified as a novel mixed 5-HT(1A)/5-HT(3) ligand with high affinity for both serotonin receptors and excellent selectivity over alpha(1)-adrenergic and dopamine D(2) receptors. This compound was characterized as a partial agonist at 5-HT(1A)Rs and a 5-HT(3)R antagonist, and was effective in preventing the cognitive deficits induced by muscarinic receptor blockade in a passive avoidance learning test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / metabolism*
  • Benzimidazoles / pharmacology
  • Drug Design
  • Ligands
  • Mice
  • Piperazines / chemical synthesis
  • Piperazines / metabolism*
  • Piperazines / pharmacology
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Rats
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Receptors, Serotonin, 5-HT3 / metabolism*

Substances

  • Benzimidazoles
  • Ligands
  • Piperazines
  • Receptors, Serotonin, 5-HT3
  • Receptor, Serotonin, 5-HT1A