Structure-Based Design, Synthesis And Screening Of The Xanthine Oxidase Inhibitors

Gout is due to the excessive of uric acid owing to the metabolism disorder of purine in vivo. According to Chinese Disease Control Center's latest survey, with the improvement of people's living standard and the speeding up of people's living pace, the incidence rate of gout is rising year by year, which is higher than the average level of the World's. Gout has become the leader of the twenty obstinate diseases in the 21st century. The metabolism disorder of purine and intaking excessive purine both cause the excessive of purine in vivo, which cause excess of uric acid, depositing in joints and thus causing gout. The statistics shows that 90% of the patients can suffer from sexual impotence, nephritis, calculus, heart disease and so on; 50% of the patients can easily become disabled because of the joint's deformation cauesd by the disease; 30% of the patients can easily cause uremia and exhaustion of kidney which result in death. Therefore, the therapy of gout has important reality significance.The direct cause of gout is the high level of uric acid in vivo, so decreasing the level of uric acid can cure gout. The study shows that xanthine oxidase inhibitors can cure gout and have bright prospect. It can inhibit the activity of xanthine oxidase and prevent purine from conversing uric acid, and decrease the level of uric acid, thus curing gout.This essay bases on the structures of xanthine oxidase crystal and inhibitor TEI-6720. The program DOCK and FLEXX were used to simulate the interaction between compounds and ligand binding domain to design a series of compounds.In this study, 15 of two series of compounds were synthesized. All of their structures were identified by ~1H-NMR and MS spectra.