Synthesis of novel N-substitutedphenyl-6-oxo-3-phenylpyridazine derivatives as cyclooxygenase-2 inhibitors

Some novel non-ulcerogenic N-substitutedphenyl-6-oxo-3-phenylpyridazines as COX-2 inhibitors have been developed (Supplementary material Appendix1). The novel aldehyde3was prepared by reacting 6-phenylpyridazin-3(2H)-one with 4-fluorobenzaldehyde. The aldehyde3was 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 compounds4a(IC50= 17.45 nm;p< .05),4b(IC50= 17.40 nm;p <.05),5a(IC50= 16.76 nm;p< .05), and10(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 of4a,4b,5a, and10. Thein vivoanti-inflammatory profile of4a,4b,5a, and10was also superior to celecoxib and indomethacin. The compounds4b,5a, and10revealed no gastric ulcerogenic effects, wherein the compound4aproduced almost negligible gastric ulcerogenic effects than celecoxib and indomethacin. The compounds4a,4b,5a, and10have been postulated as promising non-ulcerogenic COX-2 inhibitors.