Design and synthesis of pyrazolo[3,4-d]pyridazine 5,6-dioxides as novel NO-donors

A simple and effective protocol for the synthesis of 2H-pyrazolo[3,4-d]pyridazine 5,6-dioxides includes a transformation of accessible 3,4-diacetyl-5-methyl-1H-pyrazoles into the corresponding 1,4-dioximes followed by their N₂O₄- mediated oxidative cyclization. All transformations proceed under mild conditions in good to high yields. According to the Griess assay, synthesized 2H-pyrazolo[3,4-d]pyridazine 5,6-dioxides showed promising NO-donor profiles producing NO in a wide range of concentrations.