Synthesis of 1,2-Diarylethylidene hydrazone derivatives as potential antiseizure agents

A design of new antiepileptics is based on the existence of different pharmacophores that were established through the analysis of structural characteristics of clinically effective drugs as well as other antiepileptic compounds [1]. In the literatures [2] it is well documented that one of the important core fragments is defined by presence of: i) hydrogen donor/acceptor unit,ii) one electron donor atom and iii) a hydrophobic domain (aryl ring substituted/unsubstituted). This common template was found in the structures of first generation, however well-established antiepileptics such as carbamazepine or phenytoin, among the newest drugs e.g. Felbamate or in the second generation antiepileptic drugs and the drugs in clinical trial. Much efforts devoted in the recent years based on the pharmacophore model for the development of novel therapeutics resulted in the availability of several newer drugs (such astiagabine, lamotrigine) as promising antiepileptics[3].Therefore, continued search for novel antiepileptic drugs with less toxicity and more selectivity to be an area of investigation in the field of medicinal chemistry. In this article the aim of synthesizing derivatives of 1,2-diarylethylidene hydrazone derivatives 4 by thioanisol 1 and aryl acetic acid derivatives 2during the two-step reaction as potential antiseizure agents (Figure 1). Structure of compounds and intermediates have been identified to instrumental analysis techniques such as Mass, IR, 1H and 13C NMR.