Study On The Synthesis And Biological Activity Of Novel Pyrimidine Nucleoside Derivatives

A large number of modified nucleoside derivatives demonstrated variousanti-tumor, antiviral and other biological activity, and a number of new drugs havebeen approved for clinical studies or treatment HCV, HIV, HBV, anticancer and othercritical diseases, such as Gemcitabine, Capacitabine, Nelarabine, Decitabine,Azvudine and so on. Pyrimidine nucleoside derivatives represent an important classof biologically active compounds that have been extensively explored for theirantiviral, antitumor, and other properties such as Fluorouracil, Tegafur, Carmofur,Elacytarabine, Sapacitabine,5-Azacytidine,2’-Deoxy-2’,2’-difluorocytidine and soon. Despite various studies of modified Pyrimidine nucleosides, there is still a needfor the design of new analogues and development of novel nucleoside-basedtherapeutics. In particular, there is a need for new therapies for the treatment ofdrug-resistant tumors and viruses.Fluorine atom demonstrated its favorable physicochemical, pharmacokineticpharmacodynamics, pharmacological, safety and other in vivo and in vitro activitieson a number of drugs with anticancer, antiviral, anti-inflammatory, antibacterial,central nervous system (CNS) and other therapeutic applications. SomeN3-substituted uridines had been reported to be a sleep-promoting substance and werefound to have CNS-depressant effects. It would be essential to investigate thecharacteristic combination of N3-substitution and2’-fluorine, and to explore thecorresponding biological potential.Herein, we report the synthesis of forty six N3-modified pyrimidine nucleosidederivatives, of which forty three are novel compounds, including N3-substituteduridines1a-1n (Scheme2-1),2’-deoxy-2’-fluoro-N3-substituted uridines2a-2p(Scheme3-1) and2’-deoxy-2’-fluoro-N3-substituted-beta-D-arabinouridines3a-3p(Scheme4-1). The evaluations of their in vitro antitumor and antiviral activities werein progress.