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The First 5'-Phosphorylated 1,2,3-Triazolyl Nucleoside Analogues with Uracil and Quinazoline-2,4-Dione Moieties: A Synthesis and Antiviral Evaluation
- Source :
- Molecules; Volume 27; Issue 19; Pages: 6214
- Publication Year :
- 2022
-
Abstract
- A series of 5′-phosphorylated (dialkyl phosphates, diaryl phosphates, phosphoramidates, H-phosphonates, phosphates) 1,2,3-triazolyl nucleoside analogues in which the 1,2,3-triazole-4-yl-β-D-ribofuranose fragment is attached via a methylene group or a butylene chain to the N-1 atom of the heterocycle moiety (uracil or quinazoline-2,4-dione) was synthesized. All compounds were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1). Antiviral assays revealed three compounds, 13b, 14b, and 17a, which showed moderate activity against influenza virus A (H1N1) with IC50 values of 17.9 μM, 51 μM, and 25 μM, respectively. In the first two compounds, the quinazoline-2,4-dione moiety is attached via a methylene or a butylene linker, respectively, to the 1,2,3-triazole-4-yl-β-D-ribofuranosyl fragment possessing a 5′-diphenyl phosphate substituent. In compound 17a, the uracil moiety is attached via the methylene unit to the 1,2,3-triazole-4-yl-β-D-ribofuranosyl fragment possessing a 5′-(phenyl methoxy-L-alaninyl)phosphate substituent. The remaining compounds appeared to be inactive against influenza virus A/PR/8/34/(H1N1). The results of molecular docking simulations indirectly confirmed the literature data that the inhibition of viral replication is carried out not by nucleoside analogues themselves, but by their 5′-triphosphate derivatives.
- Subjects :
- Organic Chemistry
Organophosphonates
Pharmaceutical Science
Nucleosides
Alkenes
Triazoles
Antiviral Agents
nucleoside analogues
nucleotides
1,2,3-triazole
antivirals
influenza virus
click chemistry
Analytical Chemistry
Phosphates
Molecular Docking Simulation
Structure-Activity Relationship
Influenza A Virus, H1N1 Subtype
Chemistry (miscellaneous)
Drug Discovery
Quinazolines
Molecular Medicine
Physical and Theoretical Chemistry
Uracil
Subjects
Details
- ISSN :
- 14203049
- Volume :
- 27
- Issue :
- 19
- Database :
- OpenAIRE
- Journal :
- Molecules (Basel, Switzerland)
- Accession number :
- edsair.doi.dedup.....ae8534726535f70572fc60e94e69f2f7