Design, Synthesis and Biological Evaluation of Novel Trifluoromethylated Dipeptide Mimetics of Matijin‐Su as Potent Anti‐HBV Agents

A series of Matijin‐Su (MTS) derivatives were designed, synthesized and the anti‐HBV activity evaluated in vitro. Twelve compounds displayed good inhibition on HBV DNA replication with micromolar IC50 values (0.14 – 4.81 μM), among them, compounds 13d, 13n, and 13o were selected for further study. Compound 13d suppressed the HBeAg secretion with IC50 value of 2.57 μM (SI = 4.31), while had no effect on HBsAg. However, compounds 13n and 13o showed no effect to both HBeAg and HBsAg. The molecular docking studies indicated that compound 13d could form H‐bond interaction with protein residues of HBV core protein.