Identification of 1-isopropylsulfonyl-2-amine benzimidazoles as a new class of inhibitors of hepatitis B virus

A series of 1-isopropylsulfonyl-2-amine benzimidazole derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity and cytotoxicity in the HepG2.2.15 cell line. In general, these derivatives are potent HBV inhibitors (IC50 < 4 μM) with high selectivity indices (SIs > 40). Compounds 5b–e, g, j, and 9a were among the most prominent compounds, with IC50s of 0.70–2.0 μM and SIs of 41–274. The potent anti-HBV activity and safety profiles of the most promising compounds 5d and j (IC50s = 0.70 μM, SIs > 120) demonstrate the potential of this series of benzimidazoles for the development of new anti-HBV drugs.

Graphical abstractSynthesis of a series of 1-isopropylsulfonyl-2-amine benzimidazoles and their significant inhibitory activities against hepatitis B virus in vitro is presented.Figure optionsDownload full-size imageDownload as PowerPoint slide