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

Overview

Journal Iran J Pharm Res

Publisher Brieflands

Specialty Pharmacology

Date 2013 Nov 20

PMID 24250678

Citations 14

Authors

Sayyed Abbas Tabatabai

Saoka Barghi Lashkari

Mohammad Reza Zarrindast

Mohammadreza Gholibeikian

Abbas Shafiee

Affiliations

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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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References

Huang Q, He X, Ma C, Liu R, Yu S, Dayer C . Pharmacophore/receptor models for GABA(A)/BzR subtypes (alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2) via a comprehensive ligand-mapping approach. J Med Chem. 2000; 43(1):71-95. DOI: 10.1021/jm990341r. View

Almasirad A, Tabatabai S, Faizi M, Kebriaeezadeh A, Mehrabi N, Dalvandi A . Synthesis and anticonvulsant activity of new 2-substituted-5- [2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles and 1,2,4-triazoles. Bioorg Med Chem Lett. 2004; 14(24):6057-9. DOI: 10.1016/j.bmcl.2004.09.072. View

Clayton T, Chen J, Ernst M, Richter L, Cromer B, Morton C . An updated unified pharmacophore model of the benzodiazepine binding site on gamma-aminobutyric acid(a) receptors: correlation with comparative models. Curr Med Chem. 2007; 14(26):2755-75. DOI: 10.2174/092986707782360097. View

Zhang W, Koehler K, Zhang P, Cook J . Development of a comprehensive pharmacophore model for the benzodiazepine receptor. Drug Des Discov. 1995; 12(3):193-248. View

Zarghi A, Faizi M, Shafaghi B, Ahadian A, Khojastehpoor H, Zanganeh V . Design and synthesis of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles as benzodiazepine receptor agonists. Bioorg Med Chem Lett. 2005; 15(12):3126-9. DOI: 10.1016/j.bmcl.2005.04.018. View

Faizi M, Sheikhha M, Ahangar N, Tabatabaei Ghomi H, Shafaghi B, Shafiee A . Design, Synthesis and Pharmacological Evaluation of Novel 2-[2-(2-Chlorophenoxy) phenyl]-1,3,4-oxadiazole Derivatives as Benzodiazepine Receptor Agonists. Iran J Pharm Res. 2014; 11(1):83-90. PMC: 3876560. View

Zarghi A, Tabatabai S, Faizi M, Ahadian A, Navabi P, Zanganeh V . Synthesis and anticonvulsant activity of new 2-substituted-5-(2-benzyloxyphenyl)-1,3,4-oxadiazoles. Bioorg Med Chem Lett. 2005; 15(7):1863-5. DOI: 10.1016/j.bmcl.2005.02.014. View

MORPURGO C . A new design for the screening of CNS-active drugs in mice. A multi-dimensional observation procedure and the study of pharmacological interactions. Arzneimittelforschung. 1971; 21(11):1727-34. View

Mohler H, Fritschy J, Rudolph U . A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2001; 300(1):2-8. DOI: 10.1124/jpet.300.1.2. View

10.

Mahdavi M, Akbarzadeh T, Sheibani V, Abbasi M, Firoozpour L, Tabatabai S . Synthesis of Two Novel 3-Amino-5-[4-chloro-2-phenoxyphenyl]-4H-1,2,4-triazoles with Anticonvulsant Activity. Iran J Pharm Res. 2013; 9(3):265-9. PMC: 3863441. View

11.

Lager E, Nilsson J, Nielsen E, Nielsen M, Liljefors T, Sterner O . Affinity of 3-acyl substituted 4-quinolones at the benzodiazepine site of GABA(A) receptors. Bioorg Med Chem. 2008; 16(14):6936-48. DOI: 10.1016/j.bmc.2008.05.049. View

12.

Sieghart W . Structure and pharmacology of gamma-aminobutyric acidA receptor subtypes. Pharmacol Rev. 1995; 47(2):181-234. View

13.

Akbarzadeh T, Tabatabai S, Khoshnoud M, Shafaghi B, Shafiee A . Design and synthesis of 4H-3-(2-phenoxy)phenyl-1,2,4-triazole derivatives as benzodiazepine receptor agonists. Bioorg Med Chem. 2003; 11(5):769-73. DOI: 10.1016/s0968-0896(02)00469-8. View

14.

Filizola M, Harris D, Loew G . Development of a 3D pharmacophore for nonspecific ligand recognition of alpha1, alpha2, alpha3, alpha5, and alpha6 containing GABA(A)/benzodiazepine receptors. Bioorg Med Chem. 2000; 8(7):1799-807. DOI: 10.1016/s0968-0896(00)00112-7. View

15.

Zarghi A, Hajimahdi Z, Mohebbi S, Rashidi H, Mozaffari S, Sarraf S . Design and synthesis of new 2-substituted-5-[2-(2-halobenzyloxy)phenyl]-1,3,4-oxadiazoles as anticonvulsant agents. Chem Pharm Bull (Tokyo). 2008; 56(4):509-12. DOI: 10.1248/cpb.56.509. View