Synthesis Of The Nucleoside Phosphonates With 9-[(2-phosphonomethoxy)Ethyl] Purine For Antiviral New Drugs

Though many antiviral drugs have come out in resent years, the incidence of viral infection is still high. Especially, with the appearance of HIV and HIV virus in 1980s there set an urgent high standard for development and research of new antiviral agents. Nucleoside antiviral drugs are in the lead in research and application of the antiviral drugs. Acyclovir is first acyclic nucleoside antiviral drugs applied to clinic test, antiviral new compound (Adefovir), which belong to acyclic nucleoside phosphonates (ANPs), is found out in mechanism study of acyclovir. ANPs molecule directly link to phosphonate group, so when it come into body could avoid phosphorylation of rate-limiting step. At the same time, ANPs arouse peoples' attentions for simple structure and low toxicity. ANPs are one kind of nucleotide analogues, which a phosphonate group is linked to a purine or pyrimidine through an aliphatic chain via an ether linkage. A variety of ANPs are inhibitory to DNA virus and retrovirus infections. Adefovir Dipivoxil, which is based on Adefovir, has strong inhibitory action in vitro and vivo for hepadnavirus, retroviruses and herpes virus. The more important is Adefovir Dipivoxil has heightened sensitivity to Laminvudine resistance virus strain, so it could overcome drug resistance for long-term taking classic nucleotide medicine. In September in 2002, USA FDA authorized Adefovir Dipivoxil to cure chronic hepatitis B.We choose ADV and MCC-478 as leading compounds, keeping the fundamental pharcophore of (ANP), and substituting group are leaded to purine at 2, 6 positions such as heterocyclic, benzylamine and 4-substituted benzylamine radical. Nineteen2,6-substituted-9-[(2-phosphonomethoxy)ethyl] (PME)-purine were designed and synthesized for higher bioavailability and less toxicity which are hoped possess antiviral activity, and overcome the resistance brought by...