In this study, a series of α,β-unsaturated ketone intermediates were synthesized and subsequently converted into the corresponding oxime derivatives via reaction with hydroxylamine. During the synthesis of the ketone intermediates, alongside various isomers of the main products, bivinyl ketone was consistently obtained as a by-product. The by-products were identified using GC-MS analysis, and efforts were made to minimize their formation. The intermediates were synthesized from different benzaldehyde derivatives and ketones (including diethyl ketone and methyl ethyl ketone) under reflux in 37% HCl, 24h, yielding 60–90%. Conversion to the corresponding oximes was achieved by treatment with hydroxylamine hydrochloride and sodium hydroxide in ethanol for 7 h, affording yields of 60–85%. Finally, the synthesized oximes were evaluated for their potential biological activity by investigating their antagonistic effects on BALB/c mice. This study showed that oxime compounds, especially fluorine-based analogues, show significant potential in the resolution of CR-induced inflammation. The chemical structure of oxime with fluorine derivatives showed better performance than chlorine. Both intranasal and intraperitoneal administration showed good efficacy in pre-exposure prophylaxis and post-exposure treatment of CR.