Enaminones 9. Further studies on the anticonvulsant activity and potential type IV phosphodiesterase inhibitory activity of substituted vinylic benzamides

An improved method for the synthesis of benzamides via parallel solution-phase chemistry is presented. These compounds were evaluated for anticonvulsant activity as well as evaluation as potential inhibitors of phosphodiesterase type IV for use as antiasthmatics. 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).