The Study For Key Intermediates Synthesis Process Of PSI-7977

BackgroundPSI-7977(sofosbuvir) is a once-daily oral nucleoside analogue inhibitors,developed for chronic hepatitis C virus(HCV) infections,experimental drug sofosbuvir(PSI-7977) discovered by Pharmasset.Although once the bid is too high and has been criticized,sofosbuvir in clinical trials have shown excellent efficacy and safety,the making of Gilead Sciences Incis expected to become the market leader in HCV therapy. Studies have shown that for a wide range of broad HCV [3]genotype,PSI-7977 exhibits high potency of antiviral activity and can effectively reduce the development of drug resistance;the drug shortened half HCV treatment time. The discovery of the hepatitis C provides a shorter course of treatment without interferon therapy, and even the treatment of patients might have a cure,this is a new era in the treatment of hepatitis C.For the preparation of PSI-7977,there are three recognized patent preparation,through comparative analysis found that the advantages and disadvantages of its patent preparation focused on synthesis of a key intermediate,intermediate in the synthesis process research therefore propose to PSI-7977 key.The purposeTo investigate the synthesis of PSI-7977 line has been patented,found that there may be flaws in the design, improvement of existing patents,innovative research and new synthetic route to carry out the test preparation process,the synthetic route design is reasonable,do not even expected to achieve a partial response,simple operation high yield,low impurity final product,suitable for industrial production.MethodsBy inverse synthetic analysis,comparative analysis of select existingpatent process selection advantages and disadvantages,choose a preferred improvement patent innovation,new technology research andexperiments,and discuss the results.ConclusionThis study was to improve the preparation of a keyintermediate[4],Innovative new synthetic route and preparation, Mass production is not only better for industrialization,but also makes preparation simple and stable and controllable process route, produced significantly less impurity, reduces cost, conducive to industrial scale production,the yield is greatly improved.