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

Abstract

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 on cyclisation with substituted aromatic carboxylic acids in the presence of phosphorous oxychloride give 3-methyl-7-substituted-1-[(5-aryl-1,3, 4-oxadiazol-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)-1,3,4-oxadiazol-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, 1H NMR, 13C 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.