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.
Highlights
Amine derivatives of for probing the Results indicated that the introamine derivatives of oseltamivir carboxylate (OC) for probing the 150-cavity [17]
In silico ADME prediction suggest that the four compounds have drug-like pharmacokinetic properties
Parameters for oral absorption and cell permeability indicated the prospect of direct oral administration of the derivatives, such as 6i, 12c, 24b, and 26b
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Russel et al disclosed that group-1 neuraminidases a 150-cavity so-called adjacent to theirobservations, active sites, suggests a new binding pocket forcontain drug design. Adjacent to their active sites, which suggests a new binding pocket for drug design. 150-cavity adjacent to their active sites, which suggests a new binding pocket for drug. Was alsothat reported thatcould be induced to anposition open position binding of oseltamivir carboxylate to NA [13]. Reported as binders, including second amine derivatives been reportedbinders, as150-cavity. These derivatives inhibited at the nM level, and most of them possessed the selectivity.
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