Butyrophenone analogues in the carbazole series as potential atypical antipsychotics: synthesis and determination of affinities at D(2), 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors

Eur J Med Chem. 2000 Jan;35(1):83-95. doi: 10.1016/s0223-5234(00)00109-4.

Abstract

We describe practical and efficient routes for synthesis of 2-aminomethyl-1,2,3,9-tetrahydro-4H-carbazol-4-ones using the Fischer indole synthesis or palladium-catalysed cyclization methodologies, as well as their affinities for D(2), 5-HT(2A) and 5-HT(2C) receptors, and their activity at the 5-HT(2B) receptor. The most active compounds, 4b (QF 2003B) and 4c (QF 2004B), with a pK(i) (5-HT(2A)/D(2)) ratio of 1.28 show a potential antipsychotic profile according to Meltzer's classification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / chemical synthesis*
  • Antipsychotic Agents / metabolism*
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology
  • Butyrophenones / chemistry*
  • Carbazoles / chemical synthesis
  • Carbazoles / chemistry*
  • Carbazoles / metabolism
  • Carbazoles / pharmacology
  • Cattle
  • Cell Membrane / metabolism
  • Choroid Plexus / metabolism
  • Frontal Lobe / metabolism
  • Isoxazoles / chemical synthesis
  • Isoxazoles / metabolism
  • Isoxazoles / pharmacology
  • Male
  • Piperazines / chemical synthesis
  • Piperazines / metabolism
  • Piperazines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Serotonin / metabolism*
  • Serotonin Antagonists / pharmacology

Substances

  • Antipsychotic Agents
  • Butyrophenones
  • Carbazoles
  • Isoxazoles
  • Piperazines
  • QF 2003B
  • QF 2004B
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Serotonin Antagonists