Synthesis, Characterization and Anticonvulsant Activity of Some Novel 4, 5-Disubstituted-1, 2, 4-Triazole Derivatives

Abstract

The current therapy of epilepsy is associated with a number of side effects including sedation and hypnosis. Newer improved molecules are needed with lesser side effects and with improved physical properties. In view of these facts, a series of novel 4, 5-disubstituted-1,2,4-triazoles (6a-o) were synthesized on refluxing hydrazinecarbothiomides with an aqueous solution of sodium hydroxide starting from methyl-4-hydroxy benzoate via synthesis of an intermediate methyl 3-amino-4-hydroxybenzoate, methyl 2-substitutedphenyl-1,3-benzoxazole-5-carboxylates and 2-substitutedphenyl-1,3-benzoxazole-5-carbohydrazides. The structure of synthesized compounds was confirmed on the basis of their elemental analysis and spectral data results. All these compounds were screened for anticonvulsant activity using Maximal Electroshock and subcutaneous pentylenetetrazole method. Among the tested compounds 6g, 6h and 6m showed potent activity comparable to that of standard drugs phenytoin and carbamazepine. Compounds 6g, 6h, 6i, 6kand 6m successfully passed the rotarod test without any sign of neurological deficit.

Design, Synthesis,In Vivo, andIn SilicoEvaluation of Benzothiazoles Bearing a 1,3,4-Oxadiazole Moiety as New Antiepileptic Agents

“… 32 The standard drug phenytoin and phenobarbital are considered as references for designing the pharmacophore model of newly synthesized compounds ( Figure 1 ). 33 , 34 …”