Indoline and piperazine containing derivatives as a novel class of mixed D(2)/D(4) receptor antagonists. Part 2: asymmetric synthesis and biological evaluation

Bioorg Med Chem Lett. 2002 Nov 4;12(21):3111-5. doi: 10.1016/s0960-894x(02)00656-x.

Abstract

A series of chiral benzylpiperazinyl-1-(2,3-dihydro-indol-1-yl)ethanone derivatives were prepared and examined for their affinity at dopamine D(2) and D(4) receptors. Three compounds having D(2)/D(4) affinity ratios approximating that found for the atypical neuroleptic clozapine were further evaluated in behavioral tests of antipsychotic efficacy and motor side effects.

MeSH terms

  • Amphetamine / antagonists & inhibitors
  • Amphetamine / pharmacology
  • Animals
  • Antipsychotic Agents / metabolism
  • Antipsychotic Agents / pharmacology
  • Binding, Competitive / drug effects
  • Catalepsy / chemically induced
  • Central Nervous System Stimulants / antagonists & inhibitors
  • Central Nervous System Stimulants / pharmacology
  • Clozapine / metabolism
  • Clozapine / pharmacology
  • Dopamine Antagonists / chemical synthesis*
  • Dopamine Antagonists / pharmacology*
  • Dopamine Antagonists / toxicity
  • Dopamine D2 Receptor Antagonists*
  • Drug Evaluation, Preclinical
  • Dyskinesia, Drug-Induced / psychology
  • Half-Life
  • Haloperidol / pharmacology
  • Humans
  • In Vitro Techniques
  • Indicators and Reagents
  • Indoles / chemical synthesis*
  • Indoles / pharmacology*
  • Indoles / toxicity
  • Motor Activity / drug effects
  • Piperazines / chemical synthesis*
  • Piperazines / pharmacology*
  • Piperazines / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D4
  • Recombinant Proteins / drug effects
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antipsychotic Agents
  • Central Nervous System Stimulants
  • DRD4 protein, human
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Drd4 protein, rat
  • Indicators and Reagents
  • Indoles
  • Piperazines
  • Recombinant Proteins
  • benzylpiperazinyl-1-(2,3-dihydro-indol-1-yl)ethanone
  • Receptors, Dopamine D4
  • Amphetamine
  • Clozapine
  • Haloperidol