Research of potential antidepressant drugs with α2-adrenoreceptor antagonist and NA-uptake inhibiting properties: synthesis of 2-(1-hydroxy-2-phenoxy-2-phenyl)ethyl-4,5-dihydro-1H-imidazole derivatives

P. Dostert, P. Melloni, A. Della Torre, M. Varasi, L. Merlini, A. Bonsignori, S. Ricciardi

Research output: Contribution to journalArticlepeer-review

Abstract

A series of 2-(1-hydroxy-2-phenoxy-2-phenyl)ethyl-4,5-dihydro-1H-imidazole derivatives has been synthesized with the aim of finding potential antidepressant drugs endowed with both NA-uptake and α2-antagonist properties. The structure of the new compounds was designed by mixing the common elements present in reboxetine and α-aryloxy-benzyl derivatives of ethanolamine, both having NA-uptake inhibitory properties in vitro, and in idazoxan, a potent and selective α2-adrenoreceptor antagonist. The new hybrids allow a good fitting of the common features without the strong steric interactions occurring when the structure of reboxetine is superimposed on that of idazoxan. However, the new derivatives did not display significant interaction with the NA-uptake system and the α2-adrenoreceptors and proved inactive in the antireserpine test taken as a model of potential antidepressant activity. The possible relationship between the structural changes made in the parent molecules and the complete loss of activity on both systems is discussed.

Original languageEnglish
Pages (from-to)757-763
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume25
Issue number9
DOIs
Publication statusPublished - 1990

Keywords

  • idazoxan
  • NA-uptake inhibitors
  • reboxetine
  • α-adrenoreceptor antagonists

ASJC Scopus subject areas

  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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