Structure-activity Relationship Studies of Central Nervous System Agents. 5. Effect of the Hydrocarbon Chain on the Affinity of 4-substituted 1-(3-chlorophenyl)piperazines for 5-HT1A Receptor Site

J Med Chem. 1992 Jun 26;35(13):2369-74. doi: 10.1021/jm00091a004.

Abstract

The effect of the hydrocarbon chain of the model 4-substituted 1-(3-chlorophenyl)piperazines 12-31 on their affinity for 5-HT1A receptor sites was investigated. It was found that elongation of the 4-n-alkyl chain strongly increases the 5-HT1A affinity of the investigated compounds. The affinity reaches the maximum (Ki = 2.67 nM) for the n-hexyl derivative 20. It was shown that hydrophobic interactions of N-4 substituents of 1-arylpiperazines significantly contribute to their 5-HT1A affinity. The specific binding constant was defined as the receptor affinity of the protonated species of compounds under physiological conditions. The range of Ki(AH+) = 1 - 3 x 10(-11) M is a specific affinity limit of the investigated class of compounds at the 5-HT1A receptor sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Animals
  • Brain / metabolism
  • Central Nervous System / drug effects*
  • Hydrocarbons / chemistry*
  • Piperazines / metabolism*
  • Piperazines / pharmacology
  • Radioligand Assay
  • Rats
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism*
  • Structure-Activity Relationship
  • Substrate Specificity
  • Tetrahydronaphthalenes / chemistry

Substances

  • Hydrocarbons
  • Piperazines
  • Receptors, Serotonin
  • Tetrahydronaphthalenes
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • 1-(3-chlorophenyl)piperazine