RESUMEN
Enaminones, enamines of beta-dicarbonyl compounds, have been known for many years. Their early use has been relegated to serving as synthetic intermediates in organic synthesis and of late, in pharmaceutical development. Recently, the therapeutic potential of these entities has been realized. This review provides the background and current research in this area with emphasis of these agents as potential anticonvulsants, their proposed mechanisms of action, and as potential modulators of multidrug resistance (MDR).
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Aminas/farmacología , Anticonvulsivantes/farmacología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Epilepsia/tratamiento farmacológico , Neuronas/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Aminas/síntesis química , Aminas/metabolismo , Aminas/uso terapéutico , Animales , Anticonvulsivantes/síntesis química , Anticonvulsivantes/metabolismo , Anticonvulsivantes/uso terapéutico , Barrera Hematoencefálica/metabolismo , Cristalografía por Rayos X , Resistencia a Múltiples Medicamentos/genética , Epilepsia/genética , Epilepsia/metabolismo , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Humanos , Modelos Químicos , Estructura Molecular , Neuronas/metabolismo , Polimorfismo de Nucleótido Simple , Relación Estructura-Actividad Cuantitativa , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Structure-activity relationship studies were employed to synthesize a series of 3- and 3,4-substituted benzamides from 3-amino-2-cyclohexenones. An improved method for the synthesis of benzamides from 3-amino-2-cyclohexenones is presented which provided significantly higher yields (71-79%) for the reported compounds. NMR and X-ray structural analyses were undertaken to note the possible intra- and intermolecular interactions of the synthesized analogs. Molecular modeling studies were used to determine the minimized configuration and were compared to their X-ray structures for correlation. These new entities were evaluated as potential anticonvulsants and type IV phosphodiesterase inhibitors (PDE4).