Synthesis and structure-activity relationships of N-(3-phenylpropyl)-N′-benzylpiperazines: Potent ligands for σ1 and σ2 receptors

Roger I. Nahas, John R. Lever, Susan Z. Lever

Research output: Contribution to journalArticle

Abstract

Ten N-(3-phenylpropyl)-N′-benzylpiperazines having different substituents on the benzyl moiety were synthesized and evaluated for σ1 and σ2 receptor binding. The σ1 affinities were 0.37-2.80 nM, σ2 affinities were 1.03-34.3 nM, and selectivities, as σ21 affinity ratios, ranged from 1.4 to 52. Three compounds tested in a phenytoin shift binding assay profiled as probable σ1 antagonists. Quantitative structure-activity relationships depended on πx, MR or Es and Hammett σ values. The hydrophobicity term is negative for σ1 binding but positive for σ2 binding, indicating a major difference between the pharmacophores.

Original languageEnglish (US)
Pages (from-to)755-761
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number2
DOIs
StatePublished - Jan 15 2008
Externally publishedYes

Fingerprint

Quantitative Structure-Activity Relationship
Phenytoin
Structure-Activity Relationship
Hydrophobicity
Hydrophobic and Hydrophilic Interactions
Assays
Ligands
N-benzylpiperazine

Keywords

  • (+)-(5α,7α,8β)-N-methyl-N-[7-(pyrrolidin-1-yl)-1-oxaspiro[4,5]dec-8-yl]benzeneacetamide
  • (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine
  • (+)PPP
  • 1-(2-(3,4-dimethoxy-phenyl)ethyl)-4-(3-phenylpropyl)piperazine
  • [d-Ala,N-MePhe,Gly-ol]enkephalin
  • DAMGO
  • Phenylpiperazines
  • QSAR
  • Quantitative structure-activity relationship
  • SA4503
  • Sigma receptor
  • Structure-activity relationships
  • U69,593

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Synthesis and structure-activity relationships of N-(3-phenylpropyl)-N′-benzylpiperazines : Potent ligands for σ1 and σ2 receptors. / Nahas, Roger I.; Lever, John R.; Lever, Susan Z.

In: Bioorganic and Medicinal Chemistry, Vol. 16, No. 2, 15.01.2008, p. 755-761.

Research output: Contribution to journalArticle

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