Three novel series of nitroso derivatives (11-15), isoxazolopyrazoles (17a-c) and isoxazolo[3,4-d]pyridazines (18a-c) were prepared from the hydroxyimoyl chloride 10. In vitro COX1⧹2 inhibition activities were evaluated, both of 17b and 18a proved a promising inhibitory activity with IC50=1.12, 0.78μM in sequent. Carrageenan induced Paw edema, ulcer liability, nitric oxide (NO) release and histopathological study were determined. Most of the prepared compounds showed excellent activities. Reactions of 2-aminopyridine and enaminone with hydroxyimoyl chloride 10 were investigated and proved by 2D NMR. Molecular docking for most active compounds was operated giving a hint for compound-receptor interactions.