关键词: 核苷（酸）类似物, 抗病毒前药, 磷酸化修饰, 稳定性, 亲脂性

Abstract:

Nucleoside and nucleotide analogs are a class of antiviral prodrugs. After entering the human cells,they are gradually phosphorylated to generate nucleoside triphosphate analogues to serve as the antimetabolites. The resulted triphosphate analogues achieve the effect of disease treatment mainly by inhibiting virus replication and promoting apoptosis of infected cells. During the phosphorylation,the metabolic conversion process of nucleoside analogs activated by kinases in the cell is usually insufficient,resulting in a lower concentration of the final nucleoside triphosphate analogues,thus reducing the antiviral effect. Therefore,by directly preparing nucleotide analogs as antiviral prodrugs,the lipophilic and cleavable groups are modified on the phosphate groups to increase its stability and enhance the absorption capacity of cells,which can avoid the rate-limiting step of phosphorylation in the cell. In the end,it can effectively increase the final active nucleoside triphosphate concentration and exert a better antiviral effect. This article summarizes the development process of nucleotide analogs,and lists and analyzes the synthesis and modification methods of different types of nucleotide analogs,aiming to provide useful references for the further development of efficient and safe antiviral nucleotide analogs in the future.

Key words: nucleoside（nucleotide）analogs, antiviral prodrug, phosphorylation modification, stability, lipophilicity