Possible simple descriptors to predict relative activity of Antiepileptic Enaminones

JUAN GARRO MARTINEZ; MATÍAS ANDRADA,; ESTRADA MARIO; EDUARDO CASTRO; ZAMARBIDE GRACIELA; Z. MUCSI; IMRE G.CSIZMADIA

Los Cocos, Cordoba, Argentina

Conferencia; 9º Conferencia Latinoamericana de Físico Química Orgánica (; 2007

Recently, several enaminones, a group of organic compounds containing the conjugated system N-C=C-C=O (Figure 1), has been cited in the literature as antiepileptic agents 1, 2. There are some structural similarities among the known antiepileptics (Carbamazepine (CBZ), Phenytoin (PHYT)) and enaminones proposed as anticonvulsant drugs and their activity are comparable to that of class 1 anticonvulsants CBZ and PHYT 2-5. The present paper aims to establish a kind of relationship between the anticonvulsant activity of a certain set of compounds (Figure 1) and structural characteristics like distances (d), Taft steric constants (Es) and Hammett () parameters. A few of the set of compounds have been studied experimentally and the ED50 (mol/kg) were measure 1, 4, 6, 7. To explore this possibility, calculations were used to find the minimum energy conformations of 26 candidate molecules: 18 + 8 = 26 cyclic enaminones (Types I and II respectively in Figure 1).