Design, Synthesis And QSAR Of Novel Selective Cyclooxygenase-2 Inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) remain among the most widely prescribed drugs worldwide for their analgesic, antipyretic and anti-inflammatory activity. The identification and characterization of the isoenzyme cyclooxygenase-2 (COX-2) stimulated investigations to develop efficient NSAIDs with reduced side effects compared to classical NSAIDs. Till now three selective COX-2 inhibitors (e.g. Celecoxib) have been marketed and billions dollar sales are completed.The works below have been done: 1. Reviewed the development of COX-2 selective inhibitors and designed twoseries of target compounds with one common scaffold: sulfonyl-containing2.3-diaryl-indole.2. Synthesized 42 target compounds, all of which were identified by ~1HNMR and elemental analysis. The compound HWH8-2 was also identified by X-ray crystallography.3. Most of the analogs were evaluated in vitro and in vivo. All the compounds evaluated in vitro show good inhibition to COX-2 and selectivity, 12 of the compounds were found possessing higher activity to COX-2 and selectivity than Celecoxib. Half of the compounds evaluated in vivo were also found to be more potent than Celecoxib. Several candidates have been selected for further development.4. The 2D-QSAR studies were carried out within the inhibitors, and the Hansch equation was obtained. Compounds with the possibility of higher activity and selectivity were suggested.