Design, synthesis and anti-influenza A virus activity of novel 2,4-disubstituted quinazoline derivatives

Abstract Four 2,4-disubstituted quinazoline series containing various amide moieties were designed and synthesized as new anti-influenza A virus agents using the strategies of bio-isosterism and scaffold hopping. Many of them exhibit potent in vitro anti-influenza A virus activity and low cytotoxicity (CC50: > 100 μM). Particularly, compounds 10a5 and 17a show better activity (IC50: 3.70–4.19 μM) and higher selective index (SI: > 27.03, >23.87, respectively) against influenza A/WSN/33 virus (H1N1), opening a new direction for quinazoline derivatives in anti-influenza A virus field.