Some novel non‐ulcerogenic N‐substitutedphenyl‐6‐oxo‐3‐phenylpyridazines as COX‐2 inhibitors have been developed (Supplementary material Appendix 1). The novel aldehyde 3 was prepared by reacting 6‐phenylpyridazin‐3(2H)‐one with 4‐fluorobenzaldehyde. The aldehyde 3 was reacted with different hydrazines and thiazolidin‐4‐ones to obtain the novel N‐substitutedphenyl‐6‐oxo‐3‐phenylpyridazine derivatives. These were assessed for their anti‐inflammatory potential and gastric ulcerogenic effects. The molecular docking investigations were also undertaken. The spectroscopic data were coherent with the allocated structures of the compounds. The compounds 4a (IC₅₀ = 17.45 nm; p < .05), 4b (IC₅₀ = 17.40 nm; p < .05), 5a (IC₅₀ = 16.76 nm; p < .05), and 10 (IC₅₀ = 17.15 nm; p < .05) displayed better COX‐2 inhibitory activity than celecoxib (IC₅₀ = 17.79 nm; p < .05). These findings were consistent with the molecular docking investigations of 4a, 4b, 5a, and 10. The in vivo anti‐inflammatory profile of 4a, 4b, 5a, and 10 was also superior to celecoxib and indomethacin. The compounds 4b, 5a, and 10 revealed no gastric ulcerogenic effects, wherein the compound 4a produced almost negligible gastric ulcerogenic effects than celecoxib and indomethacin. The compounds 4a, 4b, 5a, and 10 have been postulated as promising non‐ulcerogenic COX‐2 inhibitors.

中文翻译：

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作为环氧合酶 2 抑制剂的新型 N-取代苯基-6-氧代-3-苯基哒嗪衍生物的合成。

一些新型的非致溃疡性 N-取代苯基-6-氧代-3-苯基哒嗪作为 COX-2 抑制剂被开发出来（补充材料附录 1）。通过 6-苯基哒嗪-3( 2H )-one 与 4-氟苯甲醛反应制备了新型醛3。醛3与不同的肼和噻唑啉-4-酮反应得到新型N-取代苯基-6-氧代-3-苯基哒嗪衍生物。评估了它们的抗炎潜力和胃溃疡形成作用。还进行了分子对接研究。光谱数据与化合物的分配结构一致。化合物4a (IC ₅₀ = 17.45 nm；p < .05)，4b (IC ₅₀ = 17.40 nm; p < .05)、5a (IC ₅₀ = 16.76 nm; p < .05) 和10 (IC ₅₀ = 17.15 nm; p < .05) 比塞来昔布（IC ₅₀ = 17.79 nm；p < .05）。这些发现与4a、4b、5a和10的分子对接研究一致。在体内的抗炎轮廓图4a，图4b，图5a，和10也优于塞来昔布和吲哚美辛。化合物4b、5a和10未显示出胃溃疡作用，其中化合物4a产生的胃溃疡作用与塞来昔布和吲哚美辛相比几乎可以忽略不计。化合物4a、4b、5a和10已被假定为有前景的非致溃疡性 COX-2 抑制剂。