Novel sulfonamides having dual dopamine D2 and D3 receptor affinity show in vivo antipsychotic efficacy with beneficial cognitive and EPS profile

Bioorg Med Chem Lett. 2007 Oct 1;17(19):5340-4. doi: 10.1016/j.bmcl.2007.08.015. Epub 2007 Aug 15.

Abstract

A novel series of arylsulfonamides was prepared either by automated parallel or by traditional solution-phase synthesis. Several members of this compound library were identified as high-affinity dopamine D3 and D2 receptor ligands. The most interesting representative, compound 2, showed potent antipsychotic behaviour coupled with a beneficial cognitive and EPS profile.

MeSH terms

  • Animals
  • Antipsychotic Agents / chemical synthesis*
  • Antipsychotic Agents / metabolism
  • Antipsychotic Agents / pharmacology*
  • Apomorphine / pharmacology
  • Avoidance Learning / drug effects
  • Binding, Competitive / drug effects
  • Biological Availability
  • Brain / metabolism
  • Catalepsy / chemically induced
  • Cognition / drug effects*
  • Humans
  • Indicators and Reagents
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / chemically induced
  • Quantitative Structure-Activity Relationship
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / metabolism*
  • Stereotyped Behavior / drug effects
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / metabolism
  • Sulfonamides / pharmacology*

Substances

  • Antipsychotic Agents
  • Indicators and Reagents
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Sulfonamides
  • Apomorphine