New substituted pyrazole derivatives targeting COXs as potential safe anti-inflammatory agents.

Aim: Everyday studies prove the increasing need for newer and safer agents to control cellular inflammatory response, an underlying cause for the pathophysiology of many other clinical cases. Results: Two newly designed sets of schiff 5a-h and chlacone 6a-f substituted pyrazoles were synthesized and evaluated for their in vivo/vitro anti-inflammatory activities. Most potent representatives were chosen for investigation of ulcerogenic and molecular docking properties. Conclusion: The synthesized compounds showed considerable edema inhibition percentage range if compared with celecoxib (13-93% and 58-93%, respectively) at different time intervals. Compound 6e showed the best screening results if compared with celecoxib (inhibition % = 93.62 and 93.51% at 5 h, COX-1/COX-2 selectivity index SI = 215.44 and 308.16 and ulcer index = 7.25 and 8, respectively).

Anti-inflammatory indomethacin analogs endowed with preferential COX-2 inhibitory activity.

Aim: The undeniable indomethacin potency has always suffered serious obstacles such as gastric damage. Continuous attempts to develop potent yet safe indomethacin analogs have never ceased. Results: Herein are new indole derivatives 4a-h and 5a-c, which were synthesized via Fisher indole reaction, evaluated for both their in vivo anti-inflammatory activities using rat paw edema method and their in vitro cyclooxygenase inhibitory activities. Then ulcerogenic liability, physicochemical parameters and molecular docking modeling were performed for the most potent ones. Conclusion: Promising results were obtained, where compound 4f was the best anti-inflammatory agent and preferential COX-2/COX-1 inhibitor (90.5% edema inhibition, selective index = 65.71, ulcer index = 7.3), if compared with indomethacin (86.7% edema inhibition, selective index = 0.079, ulcer index = 20.20).

Novel 4-methylsulfonylphenyl derivatives as NSAIDS with preferential COX-2 inhibition.

AIM: There has been an enormous commercial development following the introduction of selective COX-2 inhibitors. Efforts are continuously done to discover efficient and safe COX-2 inhibitors. RESULTS: A series of 4-methylsulfonylphenyl derivatives was designed, synthesized and screened for preferential inhibition of COX-2 over COX-1 isoforms and in vivo anti-inflammatory activity using the rat paw edema method. The most active ones were investigated via ulcerogenic liability and molecular docking. Physicochemical parameters were calculated for all the newly synthesized compounds. CONCLUSION: The new compounds showed clear preferential COX-2 over COX-1 inhibition. Selective indices for compounds 4, 6b and 6e were 124, 131 and 119, respectively. Compound 4 reached 71% in vivo anti-inflammatory inhibition. The compounds obeyed 'Lipinski's rule of five'.