Synthesis and antidepressant properties of novel 2-substituted 4,5-dihydro-1H-imidazole derivatives

J Med Chem. 1987 Aug;30(8):1482-9. doi: 10.1021/jm00391a034.

Abstract

A unique combination of alpha 2-adrenoreceptor antagonist and serotonin-selective reuptake inhibitory activities has been identified in a series of 2-substituted 4,5-dihydro-1H-imidazole derivatives. This combination of blocking activities has provided one of these derivatives, napamezole hydrochloride (2), with potential as an antidepressant. A discussion of the syntheses of these compounds includes a convenient method for the conversion of nitriles to imidazolines with ethylenediamine and trimethylaluminum.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antidepressive Agents*
  • Blepharoptosis / chemically induced
  • Brain / drug effects
  • Brain / metabolism
  • Chemical Phenomena
  • Chemistry
  • Dioxanes / metabolism
  • Dioxanes / pharmacology
  • Dopamine / metabolism
  • Idazoxan
  • Imidazoles / chemical synthesis
  • Imidazoles / metabolism
  • Imidazoles / pharmacology*
  • Male
  • Mice
  • Muscle Contraction / drug effects
  • Muscle, Smooth / physiology
  • Norepinephrine / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / drug effects*
  • Receptors, Adrenergic, alpha / physiology
  • Serotonin / metabolism*
  • Structure-Activity Relationship
  • Tetrabenazine / antagonists & inhibitors
  • p-Chloroamphetamine / antagonists & inhibitors

Substances

  • Antidepressive Agents
  • Dioxanes
  • Imidazoles
  • Receptors, Adrenergic, alpha
  • Serotonin
  • p-Chloroamphetamine
  • Dopamine
  • Norepinephrine
  • Idazoxan
  • Tetrabenazine