Litim, ZainebBen Abdeljaoued, AmeniAbdelhamid, AmalBouraoui, AbderrahmanOzdemir, IsmailHamdi, NaceurSoussi, Mohamed Ali2026-04-042026-04-0420262046-2069https://doi.org/10.1039/d6ra01380ehttps://hdl.handle.net/11616/109306The N-acylsulfonamide functional group constitutes a key moiety in numerous successful drugs, primarily due to its high chemical stability and favorable human tolerance profile. Herein, we report the development of a new eco-friendly and highly efficient approach for the preparation of N-acylsulfonamides. This method involves the synthesis of N-sulfonyloxaziridines via oxidation of the corresponding N-sulfonylimines, followed by a facile rearrangement into N-acylsulfonamides under mild and green conditions. The methodology afforded a diverse range of N-acylsulfonamides in good yields and high atom economy (AE). The synthesized compounds were subsequently evaluated for their in vivo anti-inflammatory activity. Specifically, the fluorinated N-acylsulfonamides 3c, 3e, and 3f exhibited potent inhibitory activity against carrageenan-induced inflammation, surpassing the reference drug (diclofenac). Analysis of the structure-activity relationship (SAR) highlighted the critical role of fluorine in enhancing this anti-inflammatory potential. Molecular docking and ADME-T studies were undertaken to elucidate the molecular mechanisms of action and predict the pharmacokinetic profile of these compounds on their biological targets.eninfo:eu-repo/semantics/openAccessOne-Pot SynthesisEfficient MethodSolvent-FreeOrganic-ReactionsAcylsulfonamidesInhibitorsAldehydesCyclooxygenaseSulfonylationAmidationArticle1618159921600010.1039/d6ra01380eWOS:001720437500001Q2