New pyrazole-pyridazine hybrids as selective COX-2 inhibitors: Design, synthesis, molecular docking, in silico studies and investigation of the anti-inflammatory potential by evaluation of TNF-α, IL-6, PGE-2 and NO in LPS-induced RAW264.7 macrophages

Trimethoxy derivatives 5f (IC 50 = 1.50 μM) and 6f (IC 50 = 1.15 μM) demonstrated higher COX-2 inhibitory activity than celecoxib. Also, they showed the highest inhibition of NO, TNF-α, IL-6, and PGE-2 production in LPS-induced RAW264.7 macrophages.