Affiliation:
1. Departamento de Química Orgánica Escuela Nacional de Ciencias Biológicas Instituto Politécnico Nacional Prolongación Manuel Carpio y Plan de Ayala 11350 Ciudad de México, México
2. Laboratorio de Bioquímica y Microbiología Escuela Superior de Medicina Instituto Politécnico Nacional Plan de San Luis y Díaz Mirón 11340 Ciudad de México México
3. Laboratorio de Química Orgánica CICATA Unidad Legaria Instituto Politécnico Nacional Legaria No. 694 11500 Ciudad de México México
Abstract
AbstractN‐Arylenaminones are highly versatile compounds which can be synthesized in relatively simple ways. In this work we explored the synthesis of the four monosubstituted N‐(4‐R‐phenyl)enaminones 3 a (R=NO2), 3 b (R=F), 3 c (R=H), and 3 d (R=OMe) with the goal of determining the influence of the substituents′ electronic effects on tautomer stability and biological activity. These compounds were analyzed by means of Density Functional Theory calculations (DFT), to evaluate the relative stability of the possible tautomers. We found that the enaminone structure is the most stable with respect to the ketoimine and iminoenol forms. In addition, all four compounds display anticonvulsant activity, with 3 d being the one that mostly increased latency and mostly decreased the number of convulsions with respect to the control group. The suggested mechanism of action involves blockage of the voltage‐dependent Na+ channels, considering that these molecules meet the structural characteristics needed to block the receptor, as is the case of the positive control molecules phenytoin (PHT) and valproic acid (VPA).