Design, synthesis, biological evaluation and in silico studies of pyrazole‐based nh2‐acyl oseltamivir analogues as potent neuraminidase inhibitors

Jiqing Ye, Lin Lin, Jinyi Xu, Paul Kay Sheung Chan, Xiao Yang, Cong Ma (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

Abstract

Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti‐influenza therapy. The 150‐cavity of NA was identified as an additional binding pocket, and novel NA inhibitors have been designed to occupy the 150‐cavity based on the structure information of oseltamivir carboxylate (OC) in complex with NA. In this study, a series of C‐5‐NH2‐acyl derivatives of OC containing the pyrazole moiety were synthesized. Several derivatives exhibited substantial inhibitory activity against NA. Moreover, in silico ADME evaluation indicated that the derivatives were drug‐like with higher oral absorption rates and greater cell permeability than OC. Additionally, molecular docking studies revealed that the derivatives interacted with both the NA enzyme active site and 150‐cavity as expected. The results provided useful information for further structural optimization of OC.

Original languageEnglish
Article number371
JournalPharmaceuticals
Volume14
Issue number4
DOIs
Publication statusPublished - Apr 2021

Keywords

  • 150‐cavity
  • Influenza virus
  • Neuraminidase inhibitor
  • Oseltamivir derivatives
  • Pyrazole

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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