Synthesis of new 2,3-dihydroquinazolin-4(1H)-one derivatives for analgesic and anti-inflammatory evaluation.

ABSTRACT

Starting from isatoic anhydrides, several new 2,3-dihydroquinazolin-4(1H)-one derivatives bearing chalcone or pyrazole or thiazole moieties at the third position were synthesized. The analgesic and anti-inflammatory activities for most compounds were studied at a dose level of 50 mg/kg via the acetic-acid-induced writhing-response method and carrageenan-induced edema method, respectively. The study showed that the chalcones bearing a 4-chlorophenyl group 4c or 4-nitrophenyl group 4b were the most active ones as analgesics. Both chalcone 4c and N-phenyl pyrazole bearing 4-methoxy phenyl group 5b showed a higher anti-inflammatory activity than celecoxib but still lower than that of diclofenac sodium. Moreover, the chalcone 4c has nearly the same ulcerogenic index as the selective cyclooxygenase-2 inhibitor celecoxib.