Synthesis Of Neuraminidase Inhibitors Related To Zanamivir

The influenza is an acute respiratory infection caused by the influenza virus that is harmful to human health, so to develop new and effective drug against influenza virus is immediate.Influenza virus neuraminidase inhibitors(NAI) is an important type of anti-influenza drug developed in recent years, based on rational drug design. Several neuraminidase inhibitors have been widely used in clinic practice such as zanamivir and oseltamivir, peramivir, etc. This work refered to the structure of zanamivir, carried out the designing synthesis and structure-activity study research, work mainly included the following several parts:(1) literature search glucosamine hydrochloride used as the starting material;(2) synthesis, through glycosidation, selective protection and deprotection, oxidation, beta elimination, ring opening,and reduction, a series of reactions, obtained the above derivatives, the reaction conditions were optimized to impove the reaction yield;(3)established a small analogue library, all new compound were characeterizaed by NMR and MS;(4) studied the structure-activity relationship, the inhibition activity to neuraminidase was detected by fluorescence assay. The synthesis of seven zanamivir analogs and the study of structure-activity relationship could provide materials and information for the further study of influenza virus drugs. The innovation of this paper is using high tolerance and high sensitiveity of zanamivir tovirus mutation to seek new influenza A neuraminidase innhibitos.