SYNTHESIS AND CHARACTERIZATION OF SOME NEW OXADIAZOLE DERIVATIVES AS ANTICONVULSANT AGENTS

Kalpana Divekar*, Murugan Vedigounder, Anita Kurup and Rama Sharma

ABSTRACT

Oxadiazole have often been described as bio-isosters for amide & esters. Due to increased hydrolytic & metabolic stability of oxadiazole ring an improved, pharmacokinetic and in-vivo performance is often observed, which makes these heterocyclic ring as an important structural motif for the pharmaceutical Industry. Due to these characteristics oxadiazoles have impacted numerous areas of drug discovery like muscarinic antagonists, benzodiazepines receptor partial agonists, dopamine transporters, antirhinovirals, growth hormone secretagogues, 5-HT antagonists, antispasmodics, nematocidals, fungicidal & microbicides, analgesics, anti- inflammatory, anticonvulsant, antibacterial, immunosuppressants, antiplatelet & antithrombics. In the present work, an attempt was made to synthesize some novel oxadiazole derivatives by converting the Aromatic carboxylic acids into acid esters by conventional esterification. The esters obtained were treated with hydrazine hydrate to give aromatic hydrazides. Those hydrazides on refluxing with carbon di sulfide in presence of potassium hydroxide yielded different oxadiazole derivatives. Then those oxadiazole derivatives were subjected to acetylation and aromatic group attachment. The synthesized compounds were characterized and confirmed by IR and 1HNMR spectroscopy and then screened for anticonvulsant activity. The anticonvulsant activity of newly synthesized oxadiazole derivatives was carried out by maximal electro-shock-induced convulsion method (MES) using ear electrodes in mice. Diazepam was used as positive control and normal saline served as solvent control. The investigation revealed that out of twelve newly synthesized derivatives six were found to possess anticonvulsant activity.

Keywords: Bioisosters, oxadiazoles, anticonvulsants.