2. Academic Validation
  3. Discovery of a non-zwitterionic oseltamivir analogue as a potent influenza a neuraminidase inhibitor

Discovery of a non-zwitterionic oseltamivir analogue as a potent influenza a neuraminidase inhibitor

  • Eur J Med Chem. 2020 Aug 15;200:112423. doi: 10.1016/j.ejmech.2020.112423.
Huicong Zhang 1,  Kuanglei Wang 2,  Hongxi Zhu 3,  Xiaodi Zhao 4,  Hongqian Zhao 3,  Zaiqiang Lei 3,  Binfeng Chen 3,  Fei Yang 3,  Kemin Liu 3,  Kun Zhang 5,  Jian Wang 6,  Yongshou Tian 7
Affiliations

Affiliations

  • 1 Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China.
  • 2 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China; School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, PR China; School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, PR China.
  • 3 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, PR China.
  • 4 School of Pharmacy, Sungkyunkwan University, Suwon, 16419, South Korea.
  • 5 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China; School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, PR China. Electronic address: kzhang@gdut.edu.cn.
  • 6 School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, PR China. Electronic address: wangjian2012@mail.tsinghua.edu.cn.
  • 7 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, PR China. Electronic address: tianys@syphu.edu.cn.
PMID: 32512482 DOI: 10.1016/j.ejmech.2020.112423
Abstract

The most of potent neuraminidase inhibitors as zwitterions with poor lipophilicity suffered from the poor oral bioavailability. Herein, we describe a rational journey to discover a non-zwitterionic neuraminidase inhibitor 24a containing urea. It showed potent inhibitions against neuraminidases from group 1(H5N1 and H1N1) and group 2 (H3N2) subtypes and exhibited more strong inhibitory activities against neuraminidases from H274Y mutants than oseltamivir carboxylate. Whether administrated by orally or intravenous injection, the pharmacokinetic profile of compound 24a in SD rats were improved compared to oseltamivir carboxylate.

Keywords

Influenza; Neuraminidase inhibitors; Oral bioavailability; Oseltamivir analogues; Urea.

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