SAR study of 1-aryl-4-(phenylarylmethyl)piperazines as ligands for both dopamine D2 and serotonin 5-HT1A receptors showing varying degrees of (Ant)agonism. Selection of a potential atypical antipsychotic

Chem Pharm Bull (Tokyo). 2006 Sep;54(9):1326-30. doi: 10.1248/cpb.54.1326.

Abstract

The syntheses of several 1-aryl-4-(arylpyridylmethyl)piperazines (4) and their affinities for dopamine D(2) and serotonin 5-HT(1A) receptors are described. The compounds were evaluated both in vitro and in vivo, resulting in the identification of the drug candidate SLV313 (4e) with equipotent and full D(2) receptor antagonism and 5-HT(1A) receptor agonism. Minor structural modifications in SLV313 revealed the possibility of designing compounds possessing varying degrees of partial agonism on one or both target receptors.

MeSH terms

  • Administration, Oral
  • Animals
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / chemistry*
  • Antipsychotic Agents / pharmacology*
  • Dogs
  • Dopamine D2 Receptor Antagonists*
  • Drug Design
  • Drug Evaluation, Preclinical
  • Female
  • Injections, Intravenous
  • Ligands
  • Male
  • Molecular Structure
  • Piperazines / administration & dosage
  • Piperazines / chemistry*
  • Piperazines / pharmacology*
  • Rats
  • Serotonin 5-HT1 Receptor Antagonists*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-((5-(4-fluorophenyl)-3-pyridinyl)methyl)piperazine
  • Antipsychotic Agents
  • Dopamine D2 Receptor Antagonists
  • Ligands
  • Piperazines
  • Serotonin 5-HT1 Receptor Antagonists