Structure-activity relationship studies of CNS agents, XIX: Quantitative analysis of the alkyl chain effects on the 5-HT1A and 5-HT2 receptor affinities of 4-alkyl-1-arylpiperazines and their analogs

Arch Pharm (Weinheim). 1995 Feb;328(2):143-8. doi: 10.1002/ardp.19953280210.

Abstract

The 5-HT1A and 5-HT2 receptor affinity of a set of 44 N-alkylated 1-aryl-piperazines and their analogs has been analyzed: the n-hexyl derivatives were the most potent and the most selective 5-HT1A ligands of all the investigated N-alkyl homologues. The alkyl chain may stabilize the 5-HT1A receptor-ligand complex by hydrophobic forces. A set of the alkyl substituent contributions (CHT1A) for prediction of the 5-HT1A affinity of N-alkyl derivatives of 1-arylpiperazines and related compounds have been defined on the basis of the Free-Wilson analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Piperazines / chemical synthesis*
  • Piperazines / pharmacokinetics
  • Radioligand Assay
  • Rats
  • Receptors, Serotonin / metabolism*
  • Serotonin Agents / chemical synthesis*
  • Serotonin Agents / pharmacology
  • Structure-Activity Relationship

Substances

  • Piperazines
  • Receptors, Serotonin
  • Serotonin Agents