Design, Synthesis, and Evaluation of a Set of Carboxylic Acid and Phosphate Prodrugs Derived from HBV Capsid Protein Allosteric Modulator NVR 3-778.

ABSTRACT: Hepatitis B virus (HBV) capsid protein (Cp) is necessary for viral replication and the maintenance of viral persistence, having become an attractive target of anti-HBV drugs. To improve the water solubility of HBV capsid protein allosteric modulator (CpAM) NVR 3-778, a series of novel carboxylic acid and phosphate prodrugs were designed and synthesized using a prodrug strategy. In vitro HBV replication assay showed that these prodrugs maintained favorable antiviral potency (EC₅₀ = 0.28-0.42 µM), which was comparable to that of NVR 3-778 (EC₅₀ = 0.38 µM). More importantly, the cytotoxicity of prodrug N8 (CC₅₀ > 256 µM) was significantly reduced compared to NVR 3-778 (CC₅₀ = 13.65 ± 0.21 µM). In addition, the water solubility of prodrug <

SUBMITTER: Ji X 

PROVIDER: S-EPMC9505734 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature