Influenza A virus (IAV), a highly pathogenic virus to human beings, is most susceptible to mutation and thus causes rapid, severe global pandemics resulting in millions of fatalities worldwide. Since resistance to the existing anti-influenza drugs is developing, innovative inhibitors with a different mode of action are urgently needed. The lead compound 6092B-E5 has proven to be an effective antiviral reagent in our previous work. Using the principles of substitution and bioisosterism of the indole ring, six series of novel anti-IAV target products were designed, synthesized and evaluated for their antiviral effect in this work. Compounds D 1 , D 3 , D 9 , G 1 , G 3 , G 12 and G 23 were identified as promising anti-IAV candidates with excellent anti-IAV efficacy (IC 50 values of 3.06 -5.77 μM) and low cytotoxicity (CC 50 values up to and beyond 100 μM). This work represents a successful application of the substitution and bioisosteric replacement strategy for the discovery of novel antiviral molecules that can be used for further structural optimization. Figure 3. IAV inhibition effect of selected compounds at different concentrations. IAV inhibition rate is the average of three independent sets of data and the values were shown as mean � SD. -1-yloxy)acetamide (G 7 ). The synthesis method is the same as that for G 1 . Column chromatography (petroleum ether/ethyl acetate = 10 : 1) to give G 7 (72 % yield). 1 H-NMR (600 MHz, CDCl 3 ): 8.34 (s, 1H), 8. 28 -8.22 (m, 1H), 7.93 -7.82 (m, 1H), 7.62 -7.54 (m, 3H), 7.52 -7.45 (m, 4H), 7.40 (t, J = 8.0, 1H), 6.87 (d, J = 7.6, 1H), 4.80 (s,
N-(4-Bromophenyl)-2-(naphthalen