Synthesis and structure-activity relationships of a new model of arylpiperazines. 3.1 2-[omega-(4-arylpiperazin-1-yl)alkyl]perhydropyrrolo- [1,2-c]imidazoles and -perhydroimidazo[1,5-a]pyridines: study of the influence of the terminal amide fragment on 5-HT1A affinity/selectivity

J Med Chem. 1997 Aug 1;40(16):2653-6. doi: 10.1021/jm970216k.

Abstract

A series of new arylpiperazine derivatives 2, which are devoid of the terminal amide fragment present in related 5-HT1A ligands, was prepared and evaluated for affinity at 5-HT1A and alpha 1 receptors. All the compounds 2 demonstrated high affinity for the 5-HT1A receptor and moderate affinity for alpha 1 receptor binding sites. Structure-activity relationship (SAR) studies suggest that there is influence of electronic factors on the no-pharmacophoric part of the alpha 1 receptor site. However there is no influence of electronic interactions on the stabilization of the 5-HT1A receptor-ligand complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / metabolism
  • Animals
  • Antihypertensive Agents / metabolism
  • Cerebral Cortex / metabolism
  • In Vitro Techniques
  • Models, Chemical
  • Piperazines / chemistry*
  • Piperazines / pharmacology
  • Prazosin / metabolism
  • Rats
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists / metabolism
  • Structure-Activity Relationship

Substances

  • Antihypertensive Agents
  • Piperazines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Prazosin