Design, Synthesis, Biological Evaluation and In Silico Studies of Pyrazole-Based NH₂-Acyl Oseltamivir Analogues as Potent Neuraminidase Inhibitors.

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 bot

SUBMITTER: Ye J 

PROVIDER: S-EPMC8073777 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature