Antioxidants are compounds that can delay, inhibit, or prevent the oxidation of materials that can be oxidized by scavenging free radicals and help in diminishing oxidative stress. They belong to different chemical classes. Recently there are studies related to pyridazinone derivatives for their antioxidant activities. Since there are evidences implicates reactive oxygen species and nitric oxide as mediators of inflammation and/or tissue damage in inflammatory and arthritic disorders it was though that compounds that have both antioxidant and anti-inflammatory activities would have been essential for the inflammatory diseases. Based on these findings a series of 2H-pyridazine-3-one and 6-chloropyridazine analogues that have antiinflammatory activity was tested in vitro on superoxide formation and effects on lipid peroxidation were determined against atocopherol. Most of the compounds have strong inhibitory effect on superoxide anion (between 84% -99%) at 10 23 M concentration. In addition, these compounds showed similar activity to a-tocopherol at 10 23 M concentrations.

Aldose reductase (AR) is an enzyme that catalyzes the conversion of glucose to sorbitol, which is in turn converted to fructose by sorbitol dehydrogenase. The increased glucose flux through this metabolic pathway has been linked to the development of diabetic complications such as neuropathy, nephropathy, retinopathy, and cataract. Inhibitors of AR thus seem to have the potential to prevent or treat diabetic complications. AR inhibitors belong to different chemical classes, one of which comprises pyridazinone analogues. At present, however, side effects and/or insufficient pharmacokinetic profiles have made most of the drug candidates undesirable. We evaluated a series of 2H-pyridazine-3-one and 6-chloropyridazine analogues via an in vitro spectrophotometric assay for their ability to inhibit rat kidney AR. The study showed that the introduction of a pyrazole ring on pyridazinone led to a marked decrease in AR inhibitory potency. Moreover, introduction of an acetic acid side chain on 2H-pyridazine-3-one and 6-chloropyridazine did not improve the AR inhibitory activity, which was an unexpected result. On the basis of preliminary AR inhibitory screening results on 2H-pyridazine-3-one and 6-chloropyridazine derivatives, we embarked on the synthesis of more derivatives to discover more active molecules.