Abstract

COMPUTATIONAL STUDY OF NAFIMIDONE: AN ANTIEPILEPTIC DRUG

Dr. M. Faiz Arshad*

ABSTRACT

Background: Nafimidone (CAS number 64212-22-2), a recently discovered and structurally different class of antiepileptic drugs is the derivative of imidazole. Nafimidone (2-(1H-imidazol-1-yl)-1-(2- naphthalenyl)ethanone) is undergoing clinical evaluation and up until now, the studies have revealed that nafimidone is a potent anticonvulsant than phenytoin and at the same time inhibitor of both carbamazepine and phenytoin metabolism. Because of this metabolic inhibition, nafimidone exhibited profound toxicity. Therefore, optimization of nafimidone as “lead” may produce a potent antiepileptic drug. Aim: The pharmacological and computational properties of nafimidone have been studied and discussed with aim to develop a drug candidate for the treatment of epilepsy by optimization of nafimidone with lesser toxicity. Materials and methods: Physico-chemical properties of nafimidone were established using ACD software free version downloaded from http://www.acdlabs.com/resources/freeware/ and Chem Draw Ultra (Version 8.0, Cambridge Soft Corporation, and USA). 1HNMR and 13CNMR spectra were generated by Chem Draw Ultra only. The chemical shift values were reported in δ part per million. The three dimensional structure of nafimidone was studied by using the software Ortep3v2. The correlation data were predicted on the basis of personal experience. Results and Conclusions: All the computational data and clinical trial results suggested that nafimidone derivatives may appear a potent drug candidate for the treatment of epilepsy if properly optimized.

Keywords: Nafimidone, anticonvulsant agent, epilepsy, ACD lab, 1HNMR, 13CNMR.