Novel Acyclic Phosphonylated 1,2,3-Triazolonucleosides with an Acetamidomethyl Linker: Synthesis and Biological Activity

A new series of 4‐substituted [(1,2,3‐triazol‐1‐yl)acetamido]methylphosphonates as acyclic nucleotide analogs were synthesized from diethyl (2‐chloroacetamido)methylphosphonate via azidation followed by 1,3‐dipolar cycloaddition with selected alkynes derived from natural nucleobases or their mimetic...

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Bibliographic Details
Published in:Archiv der Pharmazie (Weinheim) 2014-07, Vol.347 (7), p.506-514
Main Authors: Głowacka, Iwona E., Balzarini, Jan, Wróblewski, Andrzej E.
Format: Article
Language:English
Subjects:
Acetamides - chemistry
Animals
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antiviral
Antiviral Agents - chemical synthesis
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Cats
Cell Line
Cell Survival - drug effects
Cycloaddition
Cycloaddition Reaction
Cytopathogenic Effect, Viral
DNA Viruses - drug effects
HeLa Cells
Humans
Molecular Structure
Nucleotides - chemical synthesis
Nucleotides - chemistry
Nucleotides - pharmacology
Organophosphonates - chemical synthesis
Organophosphonates - chemistry
Organophosphonates - pharmacology
RNA Viruses - drug effects
Synthesis
Triazoles
Triazoles - chemical synthesis
Triazoles - chemistry
Triazoles - pharmacology
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Summary:A new series of 4‐substituted [(1,2,3‐triazol‐1‐yl)acetamido]methylphosphonates as acyclic nucleotide analogs were synthesized from diethyl (2‐chloroacetamido)methylphosphonate via azidation followed by 1,3‐dipolar cycloaddition with selected alkynes derived from natural nucleobases or their mimetics. All compounds were tested for their antiviral activities against DNA and RNA viruses as well as for cytostatic activity or cytotoxicity. Among all tested compounds, [(1,2,3‐triazol‐1‐yl)acetamido]methylphosphonate 6e substituted with the N3‐Bz‐benzuracil moiety showed activity against the vesicular stomatitis virus (EC50 = 45 µM) in HeLa cell cultures. New 4‐substituted [(1,2,3‐triazol‐1‐yl)acetamido]methylphosphonates were synthesized as acyclic nucleotide analogs and tested for their antiviral activities against DNA and RNA viruses. [(1,2,3‐Triazol‐1‐yl)‐acetamido]methylphosphonate 6e (n  = 1; R = N3‐Bz‐benzuracil) was found to be active against the vesicular stomatitis virus (EC50 = 45  µM) in HeLa cells.
ISSN:0365-6233
1521-4184
DOI:10.1002/ardp.201300468