Synthesis of new fenmetazole analogues with potential mixed α2-adrenergic antagonistic activity and noradrenaline-uptake inhibiting properties

P. Melloni, A. Della Torre, M. Meroni, P. Pevarello, M. Varasi, A. Bonsignori, M. Cini, F. Vaghi, P. Dostert

Research output: Contribution to journalArticlepeer-review

Abstract

In the search for new antidepressants with a rapid onset of action, fenmetazole analogues, bearing a second phenyl ring in a position previously shown not to be detrimental to affinity and selectivity for the α2-adrenoreceptors, were synthesized in an attempt to combine NA-uptake inhibition and blockade of the α2-adrenoreceptors in the same molecule. Some of the new molecules showed enhanced affinity and selectivity for the α2-adrenoreceptors compared to fenmetazole. Surprisingly, introduction of a phenyl ring in the structure of fenmetazole changed the agonistic action of the parent compound toward the α1-adrenoreceptors into an antagonistic effect. However, none of the new derivatives showed in vitro NA-uptake inhibitory potency substantially different from the low activity of fenmetazole in this test.

Original languageEnglish
Pages (from-to)207-213
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume26
Issue number2
DOIs
Publication statusPublished - 1991

Keywords

  • antidepressant activity
  • fenmetazole analogues
  • NA-uptake inhibition
  • α and α-adrenoreceptors
  • α-antagonism

ASJC Scopus subject areas

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

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