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 IC(50) 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.
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Authors | Deju Ye, Woo-Jin Shin, Ning Li, Wei Tang, Enguang Feng, Jian Li, Pei-Lan He, Jian-Ping Zuo, Hanjo Kim, Ky-Youb Nam, Weiliang Zhu, Baik-Lin Seong, Kyoung Tai No, Hualiang Jiang, Hong Liu |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 54
Pg. 764-70
(Aug 2012)
ISSN: 1768-3254 [Electronic] France |
PMID | 22795831
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Antiviral Agents
- Enzyme Inhibitors
- Neuraminidase
- Zanamivir
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Topics |
- Animals
- Antiviral Agents
(chemical synthesis, chemistry, pharmacokinetics, pharmacology)
- Chemistry Techniques, Synthetic
- Dogs
- Enzyme Inhibitors
(chemical synthesis, chemistry, pharmacokinetics, pharmacology)
- Influenza A Virus, H3N2 Subtype
(drug effects, enzymology)
- Influenza A Virus, H5N1 Subtype
(drug effects, enzymology)
- Madin Darby Canine Kidney Cells
- Male
- Neuraminidase
(antagonists & inhibitors)
- Rats
- Zanamivir
(chemical synthesis, chemistry, pharmacokinetics, pharmacology)
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