Synthesis of Some Novel 2,6 ‐Disubstituted Pyridazin‐3(2H)‐one Derivatives as Analgesic, Anti‐Inflammatory, and Non‐Ulcerogenic Agents

Some novel 2,6‐disubstituted pyridazine‐3(2H)‐one derivatives were synthesized and evaluated for in vitro cyclooxygenase‐2 (COX‐2) inhibitory efficacy. Compounds 2‐{[3‐(2‐methylphenoxy)‐6‐oxopyridazin‐1(6H)‐yl]methyl}‐1H‐isoindole‐1,3(2H)‐dione (5a), 2‐propyl‐6‐(o‐tolyloxy)pyridazin‐3(2H)‐one (6a), and 2‐benzyl‐6‐(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)pyridazin‐3(2H)‐one (16a) showed the most potent COX‐2 inhibitory activity with IC50 values of 0.19, 0.11, and 0.24 μM, respectively. The synthesized compounds with the highest COX‐2 selectivity indices were evaluated for their anti‐inflammatory, analgesic, and ulcerogenic activities. Compounds 6a and 16a demonstrated the most potent and consistent anti‐inflammatory activity over the synthesized compounds, which was significantly higher than that of celecoxib in the carrageenin rat paw edema model and with milder ulcer scoring than that of indomethacin in the ulcerogenicity screening. Novel 2,6‐disubstituted pyridazine‐3(2H)‐one derivatives were synthesized and evaluated for their in vitro COX‐2 inhibitory efficacy. The three most potent compounds showed IC50 values of 0.19, 0.11, and 0.24 μM, respectively. In addition, compounds 6a and 16a demonstrated anti‐inflammatory activities higher than that of celecoxib, with milder ulcer scoring than that of indomethacin.
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research