Synthesis and structure-activity relationships of new arylpiperazines: para substitution with electron-withdrawing groups decrease binding to 5-HT(1A) and D(2A) receptors

Eur J Med Chem. 2002 Jun;37(6):503-10. doi: 10.1016/s0223-5234(02)01357-0.

Abstract

Compounds in which N-phenylpiperazines were linked by a propyloxy chain to position 6 or 7 of a coumarin ring were designed and synthesised, and their affinities for 5-HT(1A) and D(2A) receptors were determined by radioligand binding assays. The influence of para substitution in the phenyl ring, substitution at position 4 of the coumarin system, and the coumarin position at which the piperazinylalkyl chain is linked was explored. Electron-withdrawing phenyl ring substituents para to the piperazine strongly reduced activity at both receptors. Binding at 5HT(1A) was influenced by the bulk of substituents at position 4 of the coumarin system, and binding at D(2A) by their electronic properties. Neither binding affinity was significantly affected by whether the piperazinylalkyl chain was inserted at position 6 or 7 of the coumarin system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Coumarins / chemical synthesis
  • Coumarins / chemistry
  • Drug Design
  • Electrons
  • Fibroblasts
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Humans
  • In Vitro Techniques
  • Indicators and Reagents
  • Mice
  • Piperazines / chemical synthesis*
  • Piperazines / pharmacology*
  • Raclopride / pharmacology
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin, 5-HT1
  • Structure-Activity Relationship

Substances

  • Coumarins
  • Indicators and Reagents
  • Piperazines
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Raclopride
  • 8-Hydroxy-2-(di-n-propylamino)tetralin