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

  • Bioorg Med Chem Lett. 2020 Jun 1;30(11):127143. doi: 10.1016/j.bmcl.2020.127143.
Minghua Wang  1 ,  Guoning Zhang  1 ,  Yujia Wang  1 ,  Juxian Wang  1 ,  Mei Zhu  1 ,  Shan Cen  2 ,  Yucheng Wang  3
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].
PMID: 32273213 DOI: 10.1016/j.bmcl.2020.127143
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.

Keywords
Anti-influenza A virus activity; Design; Quinazoline derivatives; Synthesis.