Synthesis and anticonvulsant activity of novel 2- and 3-[4-(trisubstituted pyridyl)-phenylamino]- and 2-[3- and 4-(trisubstituted pyridyl)-phenoxy]-quinoxaline derivatives

Abstract

A series of novel quinoxaline derivatives linked to a pyridine moiety through phenylamino or phenoxy residue was synthesized and evaluated as candidate anticonvulsants. The synthesis was achieved through reaction of 2,3-dichloroquinoxaline (1) with an equimolar amount of 4-aminoacetophenone to give compound 2 which is considered as an important synthon for the construction of a pyridine ring via several synthetic routs. Some compounds were synthesized through formation of the intermediate α,β-unsaturated compounds which, in turn, were allowed to react with malononitrile to give the corresponding alkoxypyridines (8-17). Compounds 18-21 were synthesized by a one-pot simple reaction between 2, the appropriate aldehyde, and malononitrile in sodium alkoxide solution. Moreover, they can be synthesized through reaction of compound 2 and arylidenemalononitrile in sodium alkoxide. The phenoxy analogues were prepared by reaction of 1 with 4-hydroxyacetophenone or 3-hydroxybenzaldehyde to give 22 and 27, respectively. These compounds, in turn, were allowed to react with malononitrile and the proper carbonyl compound in presence of sodium alkoxide in a one-pot reaction technique to give the target compounds. Biological evaluation of the prepared compounds showed that some of them are potent anticonvulsant agents. The detailed synthesis, spectroscopic and biological data are reported.