New quinazolinoneepyrimidine hybrids: Synthesis, anti-inflammatory, and ulcerogenicity studies

Research Abstract

Two groups of hybrid compounds: the quinazolinoneedihydropyrimidines and quinazolinoneepyrimidines, were synthesized. The starting derivative 3 was reacted with chloroacetyl chloride to give intermediate 5 which was condensed with the 2-mercaptopyrimidines 4aec affording compounds 6aec. These latter compoundsunderwent hydrolysis andN-alkylation reactions to give the dihydropyrimidine derivatives 7aec and 8aef, respectively. The chloro derivatives 9aec subsequently reacted with various anilines furnishing compounds 10aei. The anti-inflammatory activity of the synthesized compounds were evaluated using the carrageenan-induced rat paw oedema model and ulcer indices for the most active compounds were calculated. Five compounds were found more active and less ulcerogenic than diclofenac particularly compound 10g (IC50¼116.73 mmol/kg; ulcer index¼ 11.38). Compound 10g was also 2-fold more selective inhibitor of COX-2 than COX-1.

Research Keywords

quinazolinone-pyrimidine-anti-inflammatory-