Investigations of new pyridazinone derivatives for the synthesis of potent analgesic and anti-inflammatory compounds with cyclooxygenase inhibitory activity

Abstract

In this study we describe the synthesis of two novel 4-phenyl- and 4-(2-chlorophen-yl)-6-(5-chloro-2-oxo-3H-benzoxazol-7-yl)-3(2H)-pyridazinone derivatives (compounds 8 a 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 8 a and 8 b respectively) and COX-2 (by 37% and 28% for compounds 8 a and 8 b respectively) at a concentration of 10 μM. Furthermore, we tested the analgesic and anti-inflammatory activities of the synthesized compounds in vivo by using the p-benzoquinone-induced writhing test and the carrageenan-induced hind paw edema model, respectively. Compounds 8 a and b showed potent analgesic and anti-inflammatory activities without causing gastric lesions in the tested animals.