Structure-activity relationship studies of CNS agents. Part VIII. Bulk tolerance around the protonation center of 4-substituted 1-(3-chlorophenyl)piperazines at 5-HT1A and 5-HT2 receptors

Pol J Pharmacol Pharm. 1992 Nov-Dec;44(6):595-607.

Abstract

The effect of a steric hindrance around the protonation center of the model 4-substituted 1-(3-chlorophenyl)-piperazines 1-9 and 11-14 on their affinity for 5-HT1A and 5-HT2 receptor sites was investigated. Additional evidence for hydrophobic interactions between the N-4 hydrocarbon substituents and 5-HT1A receptors has been presented. However, the hydrophobic forces play a minor role in stabilization of the bioactive complex with 5-HT2 receptors. It has also been found that even bulky substituents around the protonation center of 1-aryl-piperazines are well tolerated at both 5-HT1A and 5-HT2 sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Brain / drug effects
  • Brain / metabolism
  • Models, Molecular
  • Piperazines / chemical synthesis
  • Piperazines / chemistry
  • Piperazines / metabolism*
  • Radioligand Assay
  • Rats
  • Receptors, Serotonin / metabolism*
  • Serotonin Receptor Agonists / chemical synthesis
  • Serotonin Receptor Agonists / chemistry
  • Serotonin Receptor Agonists / metabolism*
  • Structure-Activity Relationship

Substances

  • Piperazines
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • 1-(3-chlorophenyl)piperazine