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Assessing the oral bioavailability of difluorosialic acid prodrugs, potent viral neuraminidase inhibitors, using a snapshot PK screening assay.

Abstract：

:Difluorosialic acids (DFSAs) are potent inhibitors of viral neuraminidase that demonstrate activity against oseltamivir- and zanamivir-resistant strains of influenza. Unfortunately, low oral bioavailability precludes their development as second generation neuraminidase inhibitors for treating influenza as this leaves them unsuitable for use in an oral formulation. Herein is described the preparation of a series of DFSA prodrugs designed to increase oral bioavailability. These prodrugs were evaluated using a snapshot PK screen and stability tests, with successful candidates being further assessed with a full pharmacokinetic workup. These new prodrugs increased oral bioavailability by up to three times that seen for the parent DFSAs.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Arns S,Tan J,Sun S,Galey A,Zisman N,Ross F,Udechukwu J,Dercho S,Gusti V,Paquette J,Webb M,Bourque E,Withers SG,Liggins R

doi

10.1016/j.bmcl.2015.04.059

subject

Has Abstract

pub_date

2015-06-15 00:00:00

pages

2505-9

issue

12

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(15)00391-1

journal_volume

25

pub_type

杂志文章

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