title: Synthesis, receptor affinity and effect on pentylenetetrazole-induced seizure threshold of novel benzodiazepine analogues: 3-Substituted 5-(2-phenoxybenzyl)-4H-1,2,4-triazoles and 2-amino-5-(phenoxybenzyl)-1,3,4-oxadiazoles.
abstract: The new series of 5-(2-phenoxybenzyl)-4H-1,2,4-triazoles, possessing C-3 thio, alkylthio and ethoxy substituents, and 2-amino-5-(2-phenoxybenzyl)-1,3,4-oxadiazoles were designed and synthesized as novel benzodiazepine analogues. Most of them revealed similar to superior binding affinity to the GABAA/benzodiazepine receptor complex, relative to diazepam as the reference drug. Among them, 5-(4-chloro-2-(2-fluorophenoxy)benzyl)-3-benzylthio-4H-1,2,4-triazole (8l) showed the highest affinity (IC₅₀=0.892 nM) relative to diazepam (IC₅₀=2.857 nM) and also showed the most increase in pentylenetetrazole-induced seizure threshold relative to diazepam as the reference drug.
authors: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors: Siavash
authors: S
authors: Mashayekh
authors: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors: Narges
authors: N
authors: Rahmanipour
authors: Pharmacology and Toxicology Department, Pharmaceutical Sciences Branch and Pharmaceutical Sciences Research Center, Islamic Azad University, Tehran, Iran.
authors: Behnaz
authors: B
authors: Mahmoodi
authors: Department of Radiopharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors: Fatemeh
authors: F
authors: Ahmadi
authors: Pharmacology and Toxicology Department, Pharmaceutical Sciences Branch and Pharmaceutical Sciences Research Center, Islamic Azad University, Tehran, Iran.
authors: Dina
authors: D
authors: Motaharian
authors: Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: Soraya
authors: S
authors: Shahhosseini
authors: Pharmacology and Toxicology Department, Pharmaceutical Sciences Branch and Pharmaceutical Sciences Research Center, Islamic Azad University, Tehran, Iran.
authors: Hamed
authors: H
authors: Shafaroodi
authors: Department of Physiology & Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
authors: Hamid R
authors: HR
authors: Banafshe
authors: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors: Abbas
authors: A
authors: Shafiee
authors: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran; Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: navidpur@sina.tums.ac.ir.
authors: Latifeh
authors: L
authors: Navidpour
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008958:Models, Molecular; D015394:Molecular Structure; D010069:Oxadiazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000008:administration & dosage; D011963:Receptors, GABA-A / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D010069:Oxadiazoles; D011963:Receptors, GABA-A; D014230:Triazoles; D010433:Pentylenetetrazole
keywords: 1,2,4-Triazole; 1,3,4-Oxadiazole; Flexible benzodiazepines; PTZ-induced clonic seizure threshold; Receptor binding affinity