Design and synthesis of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles as benzodiazepine receptor agonists.
A series of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles was designed and synthesized as anticonvulsant agents. Conformational analysis and superimposition of energy minima conformers of the designed molecules on estazolam, a known benzodiazepine receptor agonist, revealed that the main proposed benzodiazepine pharmacophores were well matched. Electroshock and pentylenetetrazole-induced lethal convulsion tests showed that the introduction of an amino group in position 2 of 1,3,4-oxadiazole ring and a fluoro substituent at para position of benzylthio moiety had the best anticonvulsant activity. It seems this effect is mediated through benzodiazepine receptors mechanism.
Zarghi
Afshin
A
Department of Medicinal Chemistry, Faculty of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran 14155-6153, Iran. azarghi@yahoo.com
Faizi
Mehrdad
M
Shafaghi
Bijan
B
Ahadian
Avideh
A
Khojastehpoor
Hamid R
HR
Zanganeh
Vahideh
V
Tabatabai
Sayyed A
SA
Shafiee
Abbas
A
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology; D001569:Benzodiazepines / Q000737:chemistry / Q000378:metabolism*; D003292:Convulsants / Q000633:toxicity; D003975:Diazepam / Q000494:pharmacology; D015195:Drug Design; D004597:Electroshock; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000633:toxicity; D012640:Seizures / Q000209:etiology / Q000517:prevention & control; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D003292:Convulsants; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D010069:Oxadiazoles; D001569:Benzodiazepines; D005442:Flumazenil; D003975:Diazepam; D010433:Pentylenetetrazole