title: Design and synthesis of 4H-3-(2-phenoxy)phenyl-1,2,4-triazole derivatives as benzodiazepine receptor agonists.
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.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Tahmineh
authors.initials: T
authors.lastname: Akbarzadeh
authors.forename: Sayyed A
authors.initials: SA
authors.lastname: Tabatabai
authors.forename: Mohammad J
authors.initials: MJ
authors.lastname: Khoshnoud
authors.forename: Bijan
authors.initials: B
authors.lastname: Shafaghi
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology; D003292:Convulsants / Q000633:toxicity; D003975:Diazepam / Q000494:pharmacology; D015195:Drug Design; D058785:GABA-A Receptor Agonists; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors / Q000633:toxicity; D004856:Postural Balance / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: C476638:4H-3-(2-phenoxy)phenyl-1,2,4-triazole; D000927:Anticonvulsants; D003292:Convulsants; D058785:GABA-A Receptor Agonists; D007202:Indicators and Reagents; D014230:Triazoles; D003975:Diazepam; D010433:Pentylenetetrazole