Design And Synthesis Of New Aldose Reductase Inhibitors Based On Quinoxalinones

Diabetes mellitus(DM)as one of the common diseases troubled people.It is the same as cancer,cardiovascular disease threaten human death.It is relatively complex to what causes DM,but DM made the patients have long-term hyperglycemia.When the body is in the long-term hyperglycemia,diabetic complications are caused such as retinal diseases,nervous system diseases.But the market short of drugs for treating diabetic complications,the pharmaceutical industry still faces huge challenge.In experiment data,it is widely accepted that glucose enters into polyol pathway leading to the abnormal accumulation of sorbitol,which result in diabetic complications.Aldose reductase is the rate-limiting enzyme in the metabolism.Based on the research,oxidative stress is also one of prominent pathogenic mechanism.so our goal is to design and synthesize effectively aldose reductase to restrain accumulation of sorbitol and oxidative stress level.We designed an novel and simple way to synthesis target compound based on 3-choro-6-fluoro-quinoxalin-2(1H)-ones and 3-choro-7-fluoro-quinoxalin-2(1H)-ones structure.For the synthetized compounds,we have detected the biological activity in vitro and evluate molecular docking(FlexX Docking)using the Molegro Virtual Docker software.According to the experimental data,compound 50?51?52?53 are proved to be potential and high-efficient ARIs.In addition to compound 50 have resistance to oxidation.It is further proved that only hydroxyl groups can show better resistance to oxidation.In short,aldose reductase inhibitors are potential drug precursors and have the value for further study.