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 (IC(50)<4 microM) with high selectivity indices (SIs>40). Compounds 5b-e, g, j, and 9a were among the most prominent compounds, with IC(50)s of 0.70-2.0 microM and SIs of 41-274. The potent anti-HBV activity and safety profiles of the most promising compounds 5d and j (IC(50)s=0.70 microM, SIs>120) demonstrate the potential of this series of benzimidazoles for the development of new anti-HBV drugs.