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  3. Design, synthesis, and structure-activity relationships of a novel class of quinazoline derivatives as coronavirus inhibitors

Design, synthesis, and structure-activity relationships of a novel class of quinazoline derivatives as coronavirus inhibitors

  • Eur J Med Chem. 2023 Dec 5:261:115831. doi: 10.1016/j.ejmech.2023.115831.
Shengchao Zhou 1,  Kun Wang 2,  Ziwei Hu 1,  Tao Chen 1,  Yao Dong 1,  Rongmei Gao 2,  Mengyuan Wu 2,  Yuhuan Li 3,  Xingyue Ji 4
Affiliations

Affiliations

  • 1 College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu, 15021, China.
  • 2 CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 3 CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: liyuhuan@imb.pumc.edu.cn.
  • 4 College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu, 15021, China. Electronic address: jixy@suda.edu.cn.
PMID: 37813064 DOI: 10.1016/j.ejmech.2023.115831
Abstract

There remain great unmet needs to treat coronavirus infections in clinic, and the development of novel Antiviral agents is highly demanded. In this work, a phenotypic screening against our in-house compound library identified several cajanine derivatives with moderate Antiviral activity against HCoV-OC43. Based on the scaffold of cajanine, a series of quinazoline derivatives were designed employing a scaffold-hopping strategy. After an iterative structural optimization campaign, several quinazoline derivatives with potent Antiviral efficacy (EC50: ∼0.1 μM) and high selectivity (SI > 1000) were successfully identified. The preliminary mechanism of action study indicated that such quinazoline derivatives functioned at the early stage of Infection. In aggregate, this work delivered a new chemical type of coronavirus inhibitors, which could be employed not only for further development of Antiviral drugs but also as important chemical tools to delineate the target of action.

Keywords

Anticoronavirus; Quinazoline; Scaffold-hopping; Virus entry inhibitors.

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