Synthesis, binding affinity and SAR of new benzolactam derivatives as dopamine D3 receptor ligands

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1773-8. doi: 10.1016/j.bmcl.2009.01.067. Epub 2009 Jan 27.

Abstract

A series of new benzolactam derivatives was synthesized and the derivatives were evaluated for their affinities at the dopamine D(1), D(2), and D(3) receptors. Some of these compounds showed high D(2) and/or D(3) affinity and selectivity over the D(1) receptor. The SAR study of these compounds revealed structural characteristics that decisively influenced their D(2) and D(3) affinities. Structural models of the complexes between some of the most representative compounds of this series and the D(2) and D(3) receptors were obtained with the aim of rationalizing the observed experimental results. Moreover, selected compounds showed moderate binding affinity on 5-HT(2A) which could contribute to reducing the occurrence of extrapyramidal side effects as potential antipsychotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / chemical synthesis*
  • Antipsychotic Agents / pharmacology
  • Benzodiazepinones / chemical synthesis*
  • Benzodiazepinones / pharmacology
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Humans
  • Kinetics
  • Lactams / chemistry*
  • Ligands
  • Models, Chemical
  • Molecular Conformation
  • Molecular Structure
  • Piperazines / chemistry
  • Receptors, Dopamine D2 / chemistry*
  • Receptors, Dopamine D3 / chemistry*
  • Structure-Activity Relationship

Substances

  • Antipsychotic Agents
  • Benzodiazepinones
  • Lactams
  • Ligands
  • Piperazines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3