Synthesis of some new pyrimido[2′,1′:2,3]thiazolo[4,5-b]quinoxaline derivatives as anti-inflammatory and analgesic agents

Treatment of 6-aminothiouracil (1) with 2,3-dichloroquinoxaline (2) in ethanol/TEA afforded 6-amino-2-(3-chloroquinoxalin-2-ylthio)pyrimidin-4(3H)-one (3), which was refluxed in DMF to give 2-aminopyrimidoi[2',1':2,3]thiazolo[4,5-b]quinoxaline-4-one (4). Compound 4 was utilized as a key intermediate for the synthesis of a new pyrimido[2',1':2,3]thiazolo[4,5-b]quinoxaline derivatives 5-14 via the reaction with 2-chlorobenzaldehyde, 2-chlorocyclohex-1-enecarbaldehyde, 2-chlorobenzoic acid, 2,4-dichlorbenzoic acid, 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, 2-chloro-4,6-dimethylnicotinonitrile, a,alpha,beta-unsaturated ketones and isonicotinaldehyde, respectively. The chemical structures of the newly synthesized compounds were characterized by IR, NMR and mass spectral analysis. These compounds were also screened for their analgesic and anti-inflammatory activities. Some of these compounds (3, 4,9,10 and 12-14) exhibited promising activities. (C) 2010 Elsevier Masson SAS. All rights reserved.