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Chem Biol Drug Des. 2014 Jun 20. doi: 10.1111/cbdd.12382. [Epub ahead of print]
Synthesis and biological evaluation of 2-oxo-pyrazine-3-carboxamide-yl nucleoside analogues and their epimers as inhibitors of influenza A viruses.
Gao J1, Luo X, Li Y, Gao R, Chen H, Ji D.
Author information
Abstract
Novel 2-oxo-pyrazine-3-carboxamide-yl nucleoside analogues and their epimers were designed, synthesized and evaluated for their activities against influenza A viruses H1N1 and H3N2 in MDCK cells. All the compounds showed low cytotoxicities in these anti-influenza tests. One of the epimers, 4-[(1S, 3R, 4R,7R)-7-hydroxy-1-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl]-3-oxo-3,4-dihydropyrazine -2-carboxamide 8a, with high antiviral activities (IC50 = 7.41, 5.63 μM for H3N2 and H1N1, respectively) and remarkable low cytotoxicity (TC50 >200 μM), has great potential for further development as a novel anti-influenza A agent. Molecular docking of compound 8a with RNA-dependent RNA polymerase was performed to understand the binding mode between these inhibitors and the active site of RdRp and to rationalize some SARs. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
Pyrazinecarboxamide derivatives; binding mode; influenzena A H1N1; influenzena A H3N2; nucleoside analogues
PMID:
24954298
[PubMed - as supplied by publisher]
Synthesis and biological evaluation of 2-oxo-pyrazine-3-carboxamide-yl nucleoside analogues and their epimers as inhibitors of influenza A viruses.
Gao J1, Luo X, Li Y, Gao R, Chen H, Ji D.
Author information
Abstract
Novel 2-oxo-pyrazine-3-carboxamide-yl nucleoside analogues and their epimers were designed, synthesized and evaluated for their activities against influenza A viruses H1N1 and H3N2 in MDCK cells. All the compounds showed low cytotoxicities in these anti-influenza tests. One of the epimers, 4-[(1S, 3R, 4R,7R)-7-hydroxy-1-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl]-3-oxo-3,4-dihydropyrazine -2-carboxamide 8a, with high antiviral activities (IC50 = 7.41, 5.63 μM for H3N2 and H1N1, respectively) and remarkable low cytotoxicity (TC50 >200 μM), has great potential for further development as a novel anti-influenza A agent. Molecular docking of compound 8a with RNA-dependent RNA polymerase was performed to understand the binding mode between these inhibitors and the active site of RdRp and to rationalize some SARs. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
Pyrazinecarboxamide derivatives; binding mode; influenzena A H1N1; influenzena A H3N2; nucleoside analogues
PMID:
24954298
[PubMed - as supplied by publisher]
