Two groups of hybrid compounds: the quinazolinone-dihydropyrimidines and quinazolinone-pyrimidines, were synthesized. The starting derivative 3 was reacted with chloroacetyl chloride to give intermediate 5 which was condensed with the 2-mercaptopyrimidines 4a-c affording compounds 6a-c. These latter compounds underwent hydrolysis and N-alkylation reactions to give the dihydropyrimidine derivatives 7a-c and 8a-f, respectively. The chloro derivatives 9a-c subsequently reacted with various anilines furnishing compounds 10a-i. 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 10 g (IC(50) = 116.73 μmol/kg; ulcer index = 11.38). Compound 10 g was also 2-fold more selective inhibitor of COX-2 than COX-1.