Synthesis, and Pharmacological Screening of Novel Sulfamoylphenylcarbamoylquinoxaline Derivatives as Anti-Inflammatory, Analgesic and Antitumour Agents

Abstract

Treatment of quinoxaline-2,3-dicarboxylic acid anhydride with some sulfonamides gave 3-sulfamoylphenylcarbamoylquinoxaline-2-carboxylic acid derivatives. While fusing the anhydride with the same sulfonamides produced the corresponding 3-sulfamoylphenylcarbamoylquinoxalines. On refluxing 3-sulfamoylphenylcarbamoyl derivatives with acetic anhydride gave the pyrrolo[3,4- d]quinoxaline derivatives. The imide linkage in the latter compound was opened via its reaction with amines under fusion conditions and quinoxalin-2,3-diamides were obtained. The pharmacological evaluation for some of the synthesised compounds revealed that in anti-inflammatory activity in chronic models, 3-{[4-(N-pyrimidin-2-ylsulfamoyl)phenyl]carbamoyl}quinoxaline-2-carboxylic acid was equipotent to the reference drug, indomethacin as well as having nonulcerogenic effect. All tested compounds showed moderate analgesic activity compared to the reference drug. The antitumour activity for the tested compounds showed that 3-{[4-(N-(5-methylisoxazol-3-yl)sulfamoyl)phenyl]carbamoyl}quinoxaline-2-carboxylic acid, 4-(1,3-dioxo-1H-pyrrolo[3,4-b]quinoxalin-2(3H)-yl)-N-(pyrimidin-2-yl)-benzenesulfonamide and N-carbamimidoyl-4-(1,3-dioxo-1H-pyrrolo[3,4-b]quinoxalin-2(3H)-yl)benzenesulfonamide were the most effective against the liver carcinoma cell line showing IC50 values 0.5, 0.79 and 1.84 IC50 μg mL−1, respectively.