Study on 2-arylthio-5-iodo pyrimidine derivatives as novel nonnucleoside inhibitors against hepatitis B virus DNA
Jianxiong Zhao1, Jing Tu2, Ningning Fan1
1Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Background:
Novel nonnucleoside hepatitis B virus inhibitors have been recently developed for the reason of drug-resistant mutations and adverse effects of nucleoside analogs. In this study, two series of 2-arylthio-5-iodo pyrimidine analogs were firstly reported as potential anti-HBV agents.
Methodology:
Target compounds were prepared according to two high-yielded synthetic routes, and their anti-HBV activities were evaluated on Hep2.2.15 and HepAD38 cell lines, respectively. To probe the mechanism of active agents, a cell-based (Huh-7) study of biochemical markers (e.g., HBeAg, HBsAg, intracellular HBV DNA and pgRNA) was performed. Furthermore, the pharmacophore models were constructed for future optimization of lead compounds.
Conclusion:
2-Arylthio-5-iodo pyrimidine derivatives firstly proved to be effective against HBV, which paves the way for future development of nonnucleoside anti-HBV agents.
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