Potent dihydroquinolinone dopamine D2 partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia

Bioorg Med Chem Lett. 2010 May 1;20(9):2983-6. doi: 10.1016/j.bmcl.2010.02.105. Epub 2010 Mar 3.

Abstract

A dihydroquinolinone moiety was found to be a potent serotonin reuptake inhibitor pharmacophore when combined with certain amines. This fragment was coupled with selected D(2) ligands to prepare a series of dual acting compounds with attractive in vitro profiles as dopamine D(2) partial agonists and serotonin reuptake inhibitors. Structure-activity studies revealed that the linker plays a key role in contributing to D(2) affinity, function, and SRI activity.

MeSH terms

  • Animals
  • Antipsychotic Agents / chemical synthesis
  • Antipsychotic Agents / chemistry*
  • Antipsychotic Agents / therapeutic use
  • Disease Models, Animal
  • Dopamine Agonists / chemical synthesis
  • Dopamine Agonists / chemistry*
  • Dopamine Agonists / therapeutic use
  • Quinolones / chemical synthesis
  • Quinolones / chemistry*
  • Quinolones / therapeutic use
  • Receptor, Serotonin, 5-HT1A / chemistry
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / metabolism
  • Schizophrenia / drug therapy*
  • Selective Serotonin Reuptake Inhibitors / chemical synthesis
  • Selective Serotonin Reuptake Inhibitors / chemistry*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Structure-Activity Relationship

Substances

  • Antipsychotic Agents
  • Dopamine Agonists
  • Quinolones
  • Receptors, Dopamine D2
  • Serotonin Uptake Inhibitors
  • Receptor, Serotonin, 5-HT1A