Design and synthesis of 4H-3-(2-phenoxy)phenyl-1,2,4-triazole derivatives as benzodiazepine receptor agonists

Bioorg Med Chem. 2003 Mar 6;11(5):769-73. doi: 10.1016/s0968-0896(02)00469-8.

Abstract

A series of new 5-substituted analogues of 4H-3-(2-phenoxy)phenyl-1,2,4-triazole and its chlorinated derivatives was designed and prepared. Conformational analysis and superimposition of energy minima conformers of the compounds on estazolam, a known benzodiazepine receptor agonist, revealed that the main proposed benzodiazepine pharmacophores were well matched. Rotarod and pentylenetetrazole-induced lethal convulsion tests showed that the introduction of an amino group in position 5 of 1,2,4-triazole ring especially in chlorinated derivatives had the best effect which was comparable with diazepam.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / chemical synthesis
  • Anticonvulsants / pharmacology
  • Convulsants / toxicity
  • Diazepam / pharmacology
  • Drug Design
  • GABA-A Receptor Agonists*
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • Pentylenetetrazole / antagonists & inhibitors
  • Pentylenetetrazole / toxicity
  • Postural Balance / drug effects
  • Seizures / chemically induced
  • Seizures / prevention & control
  • Spectrophotometry, Infrared
  • Spectrophotometry, Ultraviolet
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / pharmacology*

Substances

  • 4H-3-(2-phenoxy)phenyl-1,2,4-triazole
  • Anticonvulsants
  • Convulsants
  • GABA-A Receptor Agonists
  • Indicators and Reagents
  • Triazoles
  • Diazepam
  • Pentylenetetrazole