title: Design, Synthesis and Pharmacological Evaluation of Novel 2-[2-(2-Chlorophenoxy) phenyl]-1,3,4-oxadiazole Derivatives as Benzodiazepine Receptor Agonists.
abstract: New derivatives of 2-[2-(2-Chlorophenoxy)phenyl]-1,3,4-oxadiazole as candidates for agonistic effect on benzodiazepine receptors were synthesized. Conformational analysis and superimposition of energy minima conformers of the novel compounds on estazolam, a known benzodiazepine agonist, revealed that the main proposed benzodiazepine pharmacophores were well matched. In pharmacological evaluation, anticonvulsant activity of the compounds determined by pentylenetetrazole-induced lethal convulsion and maximal electroshock tests. The results showed that the introduction of an amino substituent in position 5 of 1,3,4- oxadiazole ring generates compound 6 that has a considerable effect. Compound 8 with a hydroxyl substituent on position 5 of 1,3,4- oxadiazole ring showed a relatively mild anticonvulsant activity, which was significantly weaker than that of diazepam and compound 6. Anticonvulsant effects of active compounds were antagonized by flumazenil, an antagonist of benzodiazepine receptors, indicating the involvement of benzodiazepine receptors in these effects.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Faizi
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Sheikhha
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Nematollah
authors.initials: N
authors.lastname: Ahangar
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Tabatabaei Ghomi
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Bijan
authors.initials: B
authors.lastname: Shafaghi
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Seyyed Abbas
authors.initials: SA
authors.lastname: Tabatabai
keywords: 1,3,4-Oxadiazoles; Anticonvulsant; Benzodiazepine receptors; Conformational analysis; Synthesis