Discovery of benzimidazole substituted 1, 2, 4-oxadiazole compounds as novel anti-HBV agents with TLR8-agonistic activities.

Hepatitis B virus (HBV) infection is a public health threat worldwide and characterized by a dysfunctional immune response. In the present work, a new series of benzimidazole substituted 1, 2, 4-oxadiazole compounds were designed as immunomodulatory anti-HBV agents. Data showed compound 11o displayed significant in vitro anti-HBV activities against wild-type and nucleos(t)ide analogues-resistant HBV with IC50 values of 0.53 and 0.44 µM, respectively. In contrast, nucleos(t)ide analogue lamivudine is only effective for wild-type HBV (IC50 < 0.1 µM) but not effective for resistant HBV (IC50 > 100 µM). Dual-luciferase reporter gene and ELISA assay revealed that 11o exhibited a dose-dependent effect on inducing TLR8-regulated NF-κB activity, and could promote the secretion of cytokines TNF-α and IL-12 in supernatant from human PBMC cells. Molecular docking studies found that 11o formed tight interactions with binding pocket residues located at the dimer interface of TLR8. Considering the potent in vitro anti-HBV activity, effective TLR8-agonistic potency, and relatively safe profile with a selectivity index (SI) value high above 37, compound 11o deserves further investigation as a potential immunomodulatory anti-HBV agent.

Organocatalytic asymmetric syntheses of 3-fluorooxindoles containing vicinal fluoroamine motifs.

An organocatalytic Mannich reaction of 3-fluorooxindoles has been developed. Using a commercially available cinchona alkaloid catalyst, a wide range of 3-fluorooxindoles was successfully reacted with N-sulfonyl aldimines to give biologically important 3-fluorooxindoles containing vicinal fluoroamine motifs with high efficiency and good enantioselectivity. This protocol uses readily available reactants and cheap organocatalysts, and it is operationally simple.

Crystal structure of 1-fluoro-1,3-di-hydro-benzo[c]thio-phene 2,2-dioxide.

In the title compound, C8H7FO2S, the thio-phene ring has an envelope conformation, with the S atom bearing the two O atoms being the flap. In the crystal, mol-ecules are linked by C-H⋯O and C-H⋯F inter-actions, generating a three-dimensional network structure.