Synthesis of some new 2-(3-methyl-7-substituted-2-oxoquinoxalinyl)-5-(aryl)1,3,4-oxadiazoles as potential non-steroidal anti-inflammatory and analgesic agents

摘要

Ethyl (3-methyl-7-substituted-2-oxoquinoxalin-1(2H)-yl) acetates 2a-c are prepared by the condensation of ethyl chloroacetate with 3-methyl-7-substituted quinoxalin-2(1H)-ones 1a-c. The reaction of 2a-c with hydrazine hydrate furnished 2-(3-methyl-7-substituted-2-oxoquinoxalin-1(2H)-yl) acetohydrazides 3a-c, which oil cyclisation with substituted aromatic carboxylic acids in the presence of phosphorous oxychloride give 3-methyl-7-substituted-1-[(5-aryl-1,3,4oxadiazol-2-yl)methyl]quinoxalin-2(1H)-ones 4a-y. Further, the compounds 3a-c on cyclisation with carbon disulphide in methanolic potassium hydroxide yielded 1-[(5-mercapto-1,3,4-oxadiazol-2-yl)methyl]-3-methyl-7-substituted quinoxalin-2(1H)-ones 5a-c. Finally, the compounds 5a-c are converted to 3-methyl-7-substituted-1-{[5-(alkylsulfanyl)-1,3,4oxadiazol-2-yl]methyl}quinoxalin-2(1H)-ones 6a-i by reacting them with different alkyl halides. The newly synthesized compounds have been characterized by IR, H-1 NMR, C-13 NMR and mass spectral data and elemental analysis. Selected compounds are screened for in vivo anti-inflammatory and analgesic activity. Few of them exhibited promising activity.