RESUMO
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.
Assuntos
Anticonvulsivantes , Benzodiazepinas/metabolismo , Desenho de Fármacos , Agonistas de Receptores de GABA-A , Oxidiazóis/síntese química , Oxidiazóis/farmacologia , Animais , Anticonvulsivantes/síntese química , Anticonvulsivantes/farmacologia , Benzodiazepinas/química , Convulsivantes/toxicidade , Diazepam/farmacologia , Eletrochoque , Flumazenil/farmacologia , Moduladores GABAérgicos/farmacologia , Camundongos , Modelos Moleculares , Estrutura Molecular , Oxidiazóis/química , Pentilenotetrazol/toxicidade , Convulsões/etiologia , Convulsões/prevenção & controle , Relação Estrutura-AtividadeRESUMO
A series of new 2-substituted-5-(2-benzyloxyphenyl)-1,3,4-oxadiazoles have been synthesized and evaluated as anticonvulsant agents. Compound 4b shows considerable anticonvulsant activity both in PTZ and MES models. It seems this effect is mediated through benzodiazepine receptors mechanism.
Assuntos
Anticonvulsivantes/síntese química , Compostos de Benzil/síntese química , Oxidiazóis/síntese química , Animais , Anticonvulsivantes/farmacologia , Compostos de Benzil/farmacologia , Eletrochoque/métodos , Oxidiazóis/farmacologia , Pentilenotetrazol , Receptores de GABA-A/metabolismo , Relação Estrutura-AtividadeRESUMO
A series of new 2-substituted-5-[2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles has been synthesized and screened for their anticonvulsant activities. Compound 3 shows considerable anticonvulsant activity both in PTZ and MES models. It seems that this effect is mediated by benzodiazepine receptors and other unknown mechanism, respectively.
Assuntos
Anticonvulsivantes , Oxidiazóis , Triazóis , Anticonvulsivantes/síntese química , Anticonvulsivantes/farmacologia , Avaliação Pré-Clínica de Medicamentos , Estrutura Molecular , Oxidiazóis/síntese química , Oxidiazóis/farmacologia , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/farmacologiaRESUMO
A series of new 5-substituted analogues of 4H-3-(2-phenoxy)phenyl-1,2,4-triazole and its chlorinated derivatives was designed and prepared. Conformational analysis and superimposition of energy minima conformers of the compounds on estazolam, a known benzodiazepine receptor agonist, revealed that the main proposed benzodiazepine pharmacophores were well matched. Rotarod and pentylenetetrazole-induced lethal convulsion tests showed that the introduction of an amino group in position 5 of 1,2,4-triazole ring especially in chlorinated derivatives had the best effect which was comparable with diazepam.
