N-Propylnoraporphin-11-O-yl carboxylic esters as potent dopamine D(2) and serotonin 5-HT(1A) receptor dual ligands

Bioorg Med Chem. 2008 Sep 15;16(18):8335-8. doi: 10.1016/j.bmc.2008.08.056. Epub 2008 Aug 28.

Abstract

A small series of N-propylnoraporphin-11-O-yl carboxylic esters with variant ester lengths were synthesized and their binding potencies at dopamine receptors (D(1), D(2)) and serotonin receptors (5-HT(1A), 5-HT(2A)) were evaluated. Monoesters 3a-f showed binding potency of 100 nM or less for the D(2) receptor, and potency of 10-30 nM for the 5-HT(1A) receptor. Butyryl ester 3d was found to be the best compound possessing the highest potency for both receptors, with K(i) values of 55 and 12 nM for D(2) and 5-HT(1A) receptors, respectively. There is no correlation between the binding potency and the length of the monoesters, but the diesters 9 and 10 were inactive for the D(2) receptor. The dual binding profile of these monoesters for the D(2) and 5-HT(1A) receptors may be useful for the treatment of neuropsychiatric disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / chemical synthesis
  • Antipsychotic Agents / pharmacology*
  • Aporphines / chemical synthesis
  • Aporphines / pharmacology*
  • Binding Sites
  • CHO Cells
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Dopamine Antagonists / chemical synthesis
  • Dopamine Antagonists / pharmacology*
  • Esters / chemical synthesis
  • Esters / pharmacology*
  • Humans
  • Ligands
  • Rats
  • Receptor, Serotonin, 5-HT1A / drug effects*
  • Receptors, Dopamine D2 / drug effects*
  • Serotonin Receptor Agonists / chemical synthesis
  • Serotonin Receptor Agonists / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antipsychotic Agents
  • Aporphines
  • Dopamine Antagonists
  • Esters
  • Ligands
  • Receptors, Dopamine D2
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A