Eur J Med Chem Discovery of a Non-Zwitterionic Oseltamivir Analogue as a Potent Influenza a Neuraminidase Inhibitor

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Eur J Med Chem


. 2020 May 12;200:112423.
doi: 10.1016/j.ejmech.2020.112423. Online ahead of print.
Discovery of a Non-Zwitterionic Oseltamivir Analogue as a Potent Influenza a Neuraminidase Inhibitor


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

• 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.