Synthesis And Studying Of Prodrugs Of PMEA And Derivatives Of Ribavirin

PMEA, 9-[2'-(phosphonomethoxy)ethyl]adenine, as a nucleotide analogue, is one kind of reverse transcriptase inhibitors. The oral prodrug of PMEA, that is its bis(pivaloyloxymethyl)ester (also named Adefovir dipivoxil or Preveon), has being evaluated in patients infected with human immunodeficiency viruses (HIV-1 and HIV-2) or the hepatitis B virus (HBV), and shown great advantages. Inevitabiely, there are some flaws with it, cytotoxinic, low bioavailablity, difficulty in permeating membrane. So, a new prodrug of PMEA, bis(5-undecyloxopentanoyloxymethyl)ester of PMEA ,was designed and synthesized, which is expected to overcome the disadvantages of other prodrugs of PMEA for adopting long-chain substitutes.In addition, we want to change PMEA to a new kind of drug with low side-effect, good absorbability, and long-life controlled releasing feature by condensed polymerization with diols. With the help of computer, a positive conclusion of the feasibility of the esterification process was drawn through the results of quantum chemical calculation.As to Ribavirin , inhibitor of inosine 5'-monophosphate dehydrogenase, the first synthetic drug with broad antiviral spectrum. It is used in combination with interferon a to treat HCV patient. Recently, it is used to against SARS and has found favorable response at the early stage of infection. Here several kinds of analogues of Ribavirin were synthesized . And we expect some of them having more antiviral bioactivity.Meantime, several derivatives of 1,2,4-trizole were synthesized, which are highly expected to be used as biomedical intermediates.