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

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

  • Eur J Med Chem. 2020 Nov 15;206:112706. doi: 10.1016/j.ejmech.2020.112706.
Guoning Zhang 1,  Minghua Wang 1,  Jianyuan Zhao 1,  Yujia Wang 1,  Mei Zhu 1,  Juxian Wang 2,  Shan Cen 3,  Yucheng Wang 4
Affiliations

Affiliations

  • 1 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, PR China.
  • 2 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, PR China. Electronic address: [email protected].
  • 3 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, PR China. Electronic address: [email protected].
  • 4 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, PR China. Electronic address: [email protected].
PMID: 32805550 DOI: 10.1016/j.ejmech.2020.112706
Abstract

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.

Keywords

Anti-influenza A virus activity; Quinazoline derivatives; Structure-activity relationships; Synthesis.

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