Synthesis and antiviral activity evaluation of acyclic 2′-azanucleosides bearing a phosphonomethoxy function in the side chain

Koszytkowska‐Stawińska, Mariola; Clercq, Erik De; Balzarini, Jan

doi:10.1016/j.bmc.2009.04.054

Cited by 16 publications

(7 citation statements)

References 32 publications

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“…The starting diethyl 2‐chloroethoxymethylphosphonate 11 54 and diethyl 2‐chloroethoxyethylphosphonate 12 55 were prepared according to the literature procedures in 83% and 80% yields, respectively. The conversion of phosphonate 11 to azidophosphonate was carried out by reaction with sodium azide in the presence of tetrabutylammonium bromide in toluene at 90°C to give diethyl 2‐azidoethoxymethylphosphonate 13 56, 57 in 73% yield. Diethyl 2‐azidoethoxyethylphosphonate 14 was prepared according to a similar procedure from diethyl 2‐chloroethoxyethylphosphonate 12 in 78% yield (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Novel 1,2,3‐Triazolonucleotides

Głowacka

Balzarini

Wróblewski

2013

Archiv der Pharmazie

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A general procedure for the preparation of 1,2,3-triazole analogs of nucleosides from diethyl 2-azidoethoxymethyl- and 2-azidoethoxyethylphosphonates was elaborated. The application of microwave irradiation shortened the reaction time to 10 min in comparison to ca. 48 h when 1,3-dipolar cycloadditions were performed under standard conditions. All compounds were evaluated in vitro for inhibitory activity against a broad variety of DNA and RNA viruses. None of the compounds were antivirally active at subtoxic concentrations. Compound 17k exhibited moderate inhibitory effects on the proliferation of human T-lymphocyte cells (IC50=64 µM for CEM).

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Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Novel 1,2,3‐Triazolonucleotides

Głowacka

Balzarini

Wróblewski

2013

Archiv der Pharmazie

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“…The starting azidophosphonates 12a , 12b , 12c , 12d , 12e , 12f , 12g , and 12h are known and were prepared according to the literature methods except for 12a , since the existing methods for the synthesis of this compound are rather discouraging in terms of application of highly toxic hydrazoic acid and lack of commercial availability of tetramethylguanidinium azide . Our experience with in situ generated ammonium azides prompted us to apply this approach also in the synthesis of 12a via displacement of a nosyl group (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of a New Series of Phosphonylated 1,2,3‐Triazoles as Acyclic Analogs of Ribavirin

Głowacka

Balzarini

Wróblewski

2013

Archiv der Pharmazie

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A novel series of phosphonylated 1,2,3-triazoles as structural acyclic analogs of ribavirin, in which the 1,2,3-triazole ring was substituted at C4' with COOMe, CONH2, CONHOH, and CH2 NHBoc groups, were synthesized from diethyl azidomethyl-, 2-azidoethyl-, 3-azidopropyl-, 4-azidobutyl-, 2-azido-1-hydroxyethyl-, 3-azido-2-hydroxypropyl-, 2-azidoethoxymethyl- and 2-azidoethoxyethylphosphonate. The efficient synthesis of diethyl azidomethylphosphonate from diethyl 4-nitrobenzenesulfonylmethylphosphonate employing the in situ formed azides is described. All synthesized compounds were evaluated in vitro for their inhibitory activity against a broad variety of RNA and DNA viruses. No antiviral activity was observed at 100 µM. Only compound 13g exhibited inhibitory effects on the proliferation of HeLa cells (IC50=169±45 µM).

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“…) was moderately active against HIV‐1 (EC 50 = 27.8 μM) together with a certain level of cytotoxicity (CC 50 = 98 μM), while the aza‐nucleoside analogue 134 (Fig. ) did not exhibit any antiviral activity against DNA and RNA viruses at subtoxic concentrations . The unsaturated derivative 135 (Fig.…”

Section: Acyclic Nucleoside Phosphonatesmentioning

confidence: 98%

“…35) did not exhibit any antiviral activity against DNA and RNA viruses at subtoxic concentrations. 152 The unsaturated derivative 135 (Fig. 35), prepared by Topalis et al, 153 was reported as a substrate for human TMP kinase, 154 but data supporting its antiviral activity were not given.…”

Section: B Anps With Fluorinated Heterocyclic Basementioning

confidence: 99%

Medicinal Chemistry of Fluorinated Cyclic and Acyclic Nucleoside Phosphonates

Baszczyňski

Janeba

2013

Medicinal Research Reviews

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The fluorine atom plays an important role in medicinal chemistry because fluorine substitution has a strong impact on the physical, chemical, and biological properties of bioactive compounds. Such fluorine modifications have also been extensively studied among the pharmaceutically important class of nucleoside phosphonates, nucleotide analogues in which the phosphate group is replaced by the enzymatically and chemically stable phosphonate moiety. The fluorinated nucleoside phosphonates abound with antiviral, antiparasitic, and anticancer properties because they are able to act as inhibitors of important enzymes of nucleoside/nucleotide metabolism. In this paper, we review the biological properties of cyclic and acyclic nucleoside phosphonates modified by the attachment of one or more fluorine atoms to various parts of the molecule, namely to nucleobases, alkylphosphonate groups, cyclic or acyclic linkers, or to prodrug moieties.

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Synthesis and antiviral activity evaluation of acyclic 2′-azanucleosides bearing a phosphonomethoxy function in the side chain

Cited by 16 publications

References 32 publications

Synthesis and Biological Evaluation of Novel 1,2,3‐Triazolonucleotides

Synthesis and Biological Evaluation of Novel 1,2,3‐Triazolonucleotides

Synthesis of a New Series of Phosphonylated 1,2,3‐Triazoles as Acyclic Analogs of Ribavirin

Medicinal Chemistry of Fluorinated Cyclic and Acyclic Nucleoside Phosphonates

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