?A preliminary theoretical study antiepileptic drugs?.

JUAN GARRO, MATÍAS ANDRADA, MARIO ESTRADA, EDUARDO CASTRO AND GRACIELA ZAMARBIDE.

Hungría

Simposio; 2nd Internacional Szent-Györgyi Symposium (Suspendido); 2006

University of Szeged-Hungary

Recently, several enaminones, a group of organic compounds containing the conjugated system N-C=C-C=O, has been cited in the literature as antiepileptic agents [1-2]. There are structural similarities among the known antiepileptics and enaminones proposed as anticonvulsant drugs. Interestingly enough, all of the above compounds have ring structures (Figure 1), while open-ring enaminones proved to be excellent prodrugs of model primary amines because of their transportability through biological membranes. In the process of drug discovery, the relationship between drug structure, drug receptor affinity and drug bio-availability plays a significant role in the viability of a drug candidate. The present paper aims to investigate the structural characteristics of open chain enaminones (Figure 2), with the assumption that they possess both characteristics: transportability through biological membranes and pharmacological effects as antiepileptics by binding to the voltage-gated sodium ion channel. To explore this possibility, density functional calculations were used to find the minimum energy conformations of nine candidate molecules. The conformational analysis was followed by the comparison of the characteristics of the structures based on graphical and superposition techniques.