Synthesis and evaluation of 3-phenylisoxazoline derivatives as non-nucleoside hepatitis B virus inhibitors

A series of new 3-phenylisoxazoline derivatives were designed and synthesized. These compounds were assayed with HepG2 2.15 cell to evaluate their anti-hepatitis B virus (HBV) activities. Results of evaluation showed that most of the compounds were effective to inhibit HBV and more effective than 3 TC (Lamivudine). Compound 33, 34, 36 and 27 among them showed strong anti-HBV activities on inhibiting secretion of HBsAg with IC50 in 4.87 μM (SI = 11.71), 7.36 μM (SI = 25.25), 37.00 μM (SI = 8.69) and 37.30 μM (SI = 13.98) respectively. Compounds 23, 37, 39 and 36 strongly inhibited secretion of HBeAg with IC50 in 12.03 μM (SI = 2.91), 15.3 μM (SI = 1.36), 16.22 μM (SI = 1.60) and 47.99 μM (SI = 6.71) respectively. As non-nucleoside agents, these compounds inhibited replication of HBV DNA. Results of molecular docking study revealed bioactive compounds bound to HBV core protein with strong interaction. Our work may provide a new group of non-nucleoside compounds as anti-HBV agents.