Design, synthesis and in vitro anti-influenza A virus evaluation of novel quinazoline derivatives containing S-acetamide and NH-acetamide moieties at C-4

It is an urgent need to develop more effective anti-influenza agents due to the emergence of highly pathogenic and drug-resistant influenza viruses. Herein, a series of 2,4-disubstituted quinazoline derivatives were designed, synthesized and their antiviral activities against influenza A virus were evaluated. Nine compounds (10a2, 16a, 16e, 16i, 16j, 16n, 16o, 16p and 16r) showed potent activity against influenza A virus (IAV) with IC50 at the low-micromole level (1.29–9.04 μM). Particularly, 16e and 16r possess good anti-IAV activity (IC50: 1.29 μM and 3.43 μM, respectively) and acceptable cytotoxicity, and inhibit the transcription and replication of viral RNA. Together with reasonable PK profiles of 16e, these results suggest their promising potential as candidates for further investigation. [Display omitted] •Novel quinazolines containing S-acetamide and NH-acetamide moieties were synthesized.•Most of compounds showed strong anti-influenza A activities and low cell cytotoxicity.•These compounds might inhibit the transcription and replication of viral RNA.•Compounds 16e with reasonable PK profiles shows better anti-IAV activity and acceptable cytotoxicity.