Investigations of New Pyridazinone Derivatives for the Synthesis of Potent Analgesic and Anti‐Inflammatory Compounds with Cyclooxygenase Inhibitory Activity

In this study we describe the synthesis of two novel 4‐phenyl‐and 4‐(2‐chlorophenyl)‐6‐(5‐chloro‐2‐oxo‐3H‐benzoxazol‐7‐yl)‐3(2H)‐pyridazinone derivatives (compounds 8a and b) and their testing as inhibitors of cyclooxygenases (COX‐1 and COX‐2). Both compounds inhibited COX‐1 (by 59 % and 61 % for compounds 8a and 8b respectively and COX‐2 (by 37 % and 28 % for compounds 8a and 8b spectively) at a concentration of 10 μM. Furthermore, we tested the analgesic and anti‐inflammatory activities of the synthesized compounds in vivo by using the pbenzoquinone‐induced writhing test and the carrageenan‐induced hind paw edema model, respectively. Compounds 8a and 8b showed potent analgesic and anti‐inflammatory activities without causing gastric lesions in the tested animals.