Screening and evaluation of rat kidney aldose reductase inhibitory activity of some pyridazine derivatives

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