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The pyridazinone core has emerged as a leading structure for fighting inflammation, with low ulcerogenic effects. Moreover, easy functionalization of various ring positions of the pyridazinone core structure makes it an attractive synthetic and therapeutic target for the design and synthesis of anti-inflammatory agents. The present review surveys the recent advances of pyridazinone derivatives as potential anti-inflammatory agents to provide insights into the rational design of more effective anti-inflammatory pyridazinones.

New cytotoxic agents based on benzothienopyrimidine scaffold were designed, synthesized, and evaluated against the MCF‐7 breast cancer line in comparison to erlotinib and letrozole as reference drugs. Eight compounds demonstrated up to 20‐fold higher anticancer activity than erlotinib, and five of these compounds were up to 11‐fold more potent than letrozole in MTT assay. The most promising compounds were evaluated for their inhibitory activity against EGFR and ARO enzymes. Compound 12, which demonstrated potent dual EGFR and ARO inhibitory activity with IC50 of 0.045 and 0.146 µM, respectively, was further evaluated for caspase‐9 activation, cell cycle analysis, and apoptosis. The results revealed that the tested compound 12 remarkably induced caspase‐9 activation (IC50 = 16.29 ng/ml) caused cell cycle arrest at the pre‐G1/G1 phase and significantly increased the concentration of cells at both early and late stage of apoptosis. In addition, it showed a higher safety profile on normal MCF‐10A cells, and higher antiproliferative activity on cancer cells (IC50 = 8.15 µM) in comparison to normal cells (IC50 = 41.20 µM). It also revealed a fivefold higher selectivity index than erlotinib towards MCF‐7 cancer cells. Docking studies were performed to rationalize the dual inhibitory activity of compound 12.