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Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities
- Source :
-
European Journal of Medicinal Chemistry . Aug2012, Vol. 54, p764-770. 7p. - Publication Year :
- 2012
-
Abstract
- Abstract: With the introduction of bioisosteres of the guanidinium group together with scaffold hopping, 35 zanamivir analogs with C-4-modification were synthesized, and their inhibitory activities against both group-1 and group-2 neuraminidase (H5N1 and H3N2) were determined. Compound D26 exerts the most potency, with IC50 values of 0.58 and 2.72 μM against N2 and N1, respectively. Further preliminary anti-avian influenza virus (AIV, H5N1) activities against infected MDCK cells were evaluated, and D5 exerts ∼58% protective against AIV infection, which was comparable to zanamivir (∼67%). In a rat pharmacokinetic study, compound D5 showed an increased plasma half-life (t 1/2) compared to zanamivir following either intravenous or oral administration. This study may represent a new start point for the future development of improved anti-AIV agents. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 02235234
- Volume :
- 54
- Database :
- Academic Search Index
- Journal :
- European Journal of Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 78164971
- Full Text :
- https://doi.org/10.1016/j.ejmech.2012.06.033