SYNTHESIS OF NOVEL 2,6-DISUBSTITUTED PYRIDAZIN-3-ONE DERIVATIVES WITH POTENTIAL ANALGESIC AND ANTI-INFLAMMATORY ACTIVITY

Non-steroid anti-inflammatory drugs (NSAIDs) which inhibit the activity of cyclooxygenases (COXs) are widely used medications for the treatment of pain an d inflammation. Cyclooxygenase catalyzes the conversion of arachidonic acid int o prostaglandin H2 as the first committed step of prostaglandin biosynthesis. This enzyme has b een known as the target of non-steroidal anti-inflammatory drugs (NSAIDs). Pyridazinone-ba sed compounds were considered to be promising candidates in the field of design an d synthesis of potent analgesic and anti-inflammatory agents esp ecially selective COX-2 inhibit ors. The diarylheterocylic structure was assumed to be important for the anti-inflammatory activity and the N-substitution pattern was absolutely required for good in vitro COX-2 inhibit ory potency. Here, we report the synthesis of novel 2,6-Disubstituted pyridazin-3-one deriva tives that are expected to have potential in vitro COX inhibiting effect resulting in analgesic and anti-inflammatory activity based on the above findings.