Design, Synthesis of Novel Quinoxaline Derivatives and their Antinociceptive Activity

Quinoxaline derivatives constitute an important class of heterocycles in drug discovery and it acts as important structural motif for the discovery of biologically efficient compounds. A series of novel quinoxaline derivatives of Schiff bases were synthesized and evaluated by antinociceptive activity. Initiation of reaction by reacting orthophenylene diamine [1] and α-ketoglutaric acid [2] and a intermediate [3] is obtained. Further refluxion of intermediate [3] yields the formation of 3-(3-Oxo-3,4dihydro-quinoxalin-2-yl)-propionic acid methyl ester[4] which was on refluxion with substituted aromatic amines results a formation of Schiff base derivatives of aromatic amines. Promoting the scheme by further refluxion of [4] and hydrazine hydrate yields the 3-(3-Oxo-3,4dihydro-quinoxalin-2-yl)-propionic acid hydrazide [11] which was condensed with different aldehydes resulted a formation of Schiff base derivatives of aldehyde. The structures of the synthesized compounds were confirmed by spectral data and elemental analysis. The synthetic compounds were screened for the analgesic activities.The compounds DIA-2 is the most potent and DIA-5, ACP-3 showed significant analgesic activity (central) comparable with pethidine. The compound ACP-4 were found to be most active and DIA-3,ACP-1,ACP-3 also shows considerable protection against writhing test (peripheral) comparable with diclofenac sodium. Quinoxaline nucleus due to its high degree of diversity has been proven useful for the development of newer pain relieving agents having improved potency and lesser toxicity.