design, synthesis and pharmacological evaluation of novel 2-[2-(2-chlorophenoxy) phenyl]-1,3,4-oxadiazole derivatives as benzodiazepine receptor agonists

نویسندگان

mehrdad faizi department of pharmacology and toxicology, school of pharmacy, shahid beheshti university of medical sciences, tehran, iran.

majid sheikhha department of medicinal chemistry, school of pharmacy, shahid beheshti university of medical sciences, tehran, iran.

nematollah ahangar pharmaceutical sciences research center and department of toxicology/pharmacology, faculty of pharmacy, mazandaran university of medical sciences, sari, iran

hamed tabatabaei ghomi department of medicinal chemistry, school of pharmacy, shahid beheshti university of medical sciences, tehran, iran.

چکیده

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.

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Design, Synthesis and Pharmacological Evaluation of Novel 2-[2-(2-Chlorophenoxy) phenyl]-1,3,4-oxadiazole Derivatives as Benzodiazepine Receptor Agonists

     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 eval...

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Design, Synthesis and Pharmacological Evaluation of Novel 2-[2-(2-Chlorophenoxy) phenyl]-1,3,4-oxadiazole Derivatives as Benzodiazepine Receptor Agonists

     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 eval...

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Design, Synthesis and Pharmacological Evaluation of Novel 2-[2-(2-Chlorophenoxy) phenyl]-1,3,4-oxadiazole Derivatives as Benzodiazepine Receptor Agonists

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 evaluatio...

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design, synthesis and anticonvulsant activity of 2-(2-phenoxy) phenyl-1,3,4-oxadiazole derivatives

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عنوان ژورنال:
the iranian journal of pharmaceutical research

جلد ۱۱، شماره ۱، صفحات ۸۳-۹۰

کلمات کلیدی
[ ' a n t i c o n v u l s a n t ' , ' b e n z o d i a z e p i n e r e c e p t o r s ' , ' s y n t h e s i s ' , 1 , 3 , 4 , ' o x a d i a z o l e s ' , ' c o n f o r m a t i o n a l a n a l y s i s ' ]

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