Discovery and biological evaluation of 2-((3-phenylisoxazol-5-yl) methoxy) benzamide derivatives as potent nucleocapsid inhibitors

A series of 2-((3-phenylisoxazol-5-yl) methoxy) benzamides derivatives were designed and synthesized, and their anti-hepatitis B virus (HBV) activities were evaluated with HepG2.2.15 cells. The results showed that compounds 10a, 10c, 10d and 10f strongly inhibited secretion of HBeAg (IC50 = 0.20, 0.07, 0.30 and 0.12 mu M, respectively, 3TC in 119.87 mu M). Compounds 8a, 8b, 10c, 10f effectively inhibited HBV DNA replication with IC50 in 7.61, 8.92, 0.10 and 1.49 mu M, respectively and were more effective than 3TC (IC50(DNA) = 13.02 mu M). Result of docking studies indicated that compounds interacted to HBV core protein and coincided to their inhibitions on HBV. This work provided new compounds with significant inhibition on HBV for further optimization and development as potential non-nucleoside anti-virus agents. Mean-while, chlorination on phenyl ring of dimethoxybenzaldehyde oxime occurred and did not follow Friedel -Crafts substitution when the oxime reacted with excess NCS.(c) 2022 Elsevier B.V. All rights reserved.