Design, Synthesis and Anticonvulsant Activity of 2-(2-Phenoxy) phenyl-1,3,4-oxadiazole Derivatives

Document Type: Research article

Authors

1 1- Department of Medicinal Chemisty School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

3 Department of Chemistry, Faculty of Basic Science, Semnan University, Semnan, Iran.

4 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Benzodiazepines are useful drugs for treatment of sleep disorders, anxiety, seizure cases and skeletal muscle cramps. Some derivatives of 2-(2-Phenoxy) phenyl-1, 3, 4-oxadiazole were synthesized as benzodiazepine receptor agonists. Conformational analysis and superimposition of energy minima conformers of the compounds on estazolam, a known benzodiazepine agonist, reveal that the main proposed benzodiazepine pharmacophores were well matched. Anticonvulsant activity of the synthesized compounds, determined by pentylenetetrazole-induced lethal convulsion test, showed that the introduction of an amino substituent in position 5 of 1,3,4- oxadiazole ring generates compound 9 which has a respectable effect. The results are in agreement with SAR of benzodiazepine receptor ligands since the elimination of electronegative substituent in position 2 of phenoxy ring or position 4 of phenyl ring reduces the anticonvulsant activity.

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