The Synthesis Of Nucleoside Antiviral Drugs

Virus were harmful to our health and even dangerous to our life. There has been more and more success in developing antiviral agents for decreasing the mortality of virus infection in clinic. But most of current antiviral agents have some disadvantages and limitations, which included the existence of reservoirs or sanctuaries for the virus(such as HIV, HBV and HCV) in vivo,toxicity, resistance issues and low oral bioavailability etc.To obtain better oral activity, three novel series total 17 analogs derived from PMPA, PMEA and GCV were synthesized and verified by MS and NMR in this thesis. The activities of compounds 1-12 were evaluated in cell models, the results demonstrated that most of them have good activities against HIV and HBV. Among them, compounds HDP-PMPA/PMEA and ODE-PMPA/PMEA showed better activities than PMPA/PMEA against HIV/HBV, the activities of compounds TDP-PMPA/PMEA were greater than PMPA against HIV, and showed similar activities against HBV.In vivo activities of compound 2, 4 and 6 were evaluated in animal models against HIV, they all showed more powerful and obviously prolonged activities than Tenofovir DF. Their bioavailability has been approved to be better than PMPA. So they had potential to be developed into clinical drugs.