Azepinoindole derivatives with high affinity for brain dopamine and serotonin receptors

Bioorg Med Chem Lett. 1998 Apr 21;8(8):983-8. doi: 10.1016/s0960-894x(98)00138-3.

Abstract

We synthesized 20 and 21 as conformationally constrained analogues of the dopamine receptor antagonist SKF-83742, as well as analogues 6-9, 16, and 18-22. Although 20 and 21 were inactive, 7, 9, and 19 showed strong binding to D-1, D-2, S-2, and alpha-1 receptors, as well as antipsychotic activity in vivo.

MeSH terms

  • Animals
  • Antipsychotic Agents / chemical synthesis*
  • Antipsychotic Agents / chemistry
  • Antipsychotic Agents / pharmacokinetics
  • Azepines / chemical synthesis*
  • Azepines / chemistry
  • Azepines / pharmacokinetics
  • Benzazepines / chemistry*
  • Brain / metabolism*
  • Dopamine Antagonists / chemical synthesis*
  • Dopamine Antagonists / chemistry
  • Dopamine Antagonists / pharmacokinetics
  • Drug Design
  • Indicators and Reagents
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacokinetics
  • Molecular Conformation
  • Molecular Structure
  • Rats
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Serotonin / metabolism*
  • Structure-Activity Relationship

Substances

  • Antipsychotic Agents
  • Azepines
  • Benzazepines
  • Dopamine Antagonists
  • Indicators and Reagents
  • Indoles
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • SK&F 83742