Study Of Novel Benzimidazole Derivatives As Inhibitors Of Hepatitis B Virus

Hepatitis B Virus (HBV) is the seventh leading global cause of death. According to the WHO, about a half of people in the world are living in the high prevalent area and350-400million people are chronically infected. Appropriately0.75million people die from the diseases caused by HBV annually. The antiviral therapy displays a key role for treatment of chronic hepatitis B. There are several antiviral agents are currently available in clinical application for the treatment of chronic HBV, such as interferon, nucleoside analogues. While they have limited efficacy in a significant proportion of patients and have severe adverse effects. Therefore, there is a pressing need to develop novel classes of antiviral agents for the treatment of HBV infection.Our research group had carried out a lot of work on this topic. The results showed that benzimidazoles have a high antiviral activity. But many synthesized compounds are not soluble, they have poor biological activated. In this paper, further study has been done. Through modified the different part of the starting points, we synthesized a series of compounds and studied the impact of the different structures or functional groups. We hope to find some factors to overcome this shortcoming.In the first part of this assay, we choosed compound with good biological activity (IC5o<1.37μM and SI>131.8) as the new benchmark compound for further optimization. A number of good antiviral activities benzimidazole derivatives with low cytotoxicity were synthesized, in which the most potent compound showed good biological activity (IC50<0.41μM and SI>81.2).We found that benzimidazole derivatives exhibited good anti-HBV activities. Recently, a large body of work reported that a set of heterocyclic benzimidazole analogues showed promising anti-HCV activity. However, there is very scarce data on the anti-HBV activity for these heterocyclic benzimidazole compounds.In the light of the above reports and our continued interest in the study of anti-HBV activity of benzimidazole compounds, a library of two structural related thiazolylbenzimidazole derivatives was designed and prepared in the second part of this assay. Their anti-HBV activity and cytotoxicity were investigated in vitro. A number of them proved to keeping potential antiviral activities (IC5o=1.1～6.1μM), with low cytotoxicity (CC50>33.3or>100μM). In summary, these compounds have simple synthetic routes and prospects for further study.