Introduction Hepatitis B virus (HBV) is a global health concern that can cause acute and chronic liver diseases. Thus, there is an urgent need to research novel anti-HBV agents. Our previous reports show that N -phenylbenzamide derivatives exert broad-spectrum antiviral effects against HIV-1, HCV, and EV71 by increasing intracellular levels of APOBEC3G (A3G). As A3G is capable of inhibiting the replication of HBV, we screened the N -phenylbenzamide derivatives against HBV. Methods In this study, a new derivative, N -(4-chlorophenyl)-4-methoxy-3-(methylamino) benzamide (IMB-0523), was synthesized and its anti-HBV activity was evaluated in vitro and in vivo. The acute toxicity and pharmacokinetic profiles of IMB-0523 were also investigated. Results Our results show that IMB-0523 has higher anti-HBV activity in both wild-type HBV (IC 50 : 1.99 µM) and drug-resistant HBV (IC 50 : 3.30 µM) than lamivudine (3TC, IC 50 : 7.37 µM in wild-type HBV, IC 50 : >440 µM in drug-resistant HBV). The antiviral effect of IMB-0523 against HBV may be due to an increased level of intracellular A3G. IMB-0523 also showed low acute toxicity (LD 50 : 448 mg/kg) in mice and promising PK properties (AUC 0-t : 7535.10±2226.73 µg·h/L) in rats. Further, IMB-0523 showed potent anti-HBV activity in DHBV-infected ducks. Conclusion Thus, IMB-0523 may be a potential anti-HBV agent with different mechanisms than current anti-HBV treatment options.
The title compound, C17H17ClN2O3·0.5C6H12, was prepared by the condensation reaction of 4-methoxy-3-(propanamido)benzoic acid with 4-chloroaniline. The Cl atom, the propionyl CH3 group and the cyclohexyl CH2 group are disordered over two sets of sites of equal occupancy in both molecules. The cyclohexane solvent molecule is disordered over two orientations which were modelled with relative occupancies of 0.484 (4) and 0.516 (4). In the crystal, there are a number of N—H⋯O hydrogen bonds, forming layers perpendicular to (001).
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