Synthesis of 1,2,3-triazolo-nucleosides via the post-triazole N-alkylation

Koszytkowska‐Stawińska, Mariola; Mironiuk‐Puchalska, Ewa; Rowicki, Tomasz

doi:10.1016/j.tet.2011.10.067

Cited by 21 publications

(9 citation statements)

References 92 publications

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“…The applicability of a 1,2,3-triazole ring as a replacement of sugar [17][18][19] or nucleobase moieties 17,[19][20][21] as well as an additional linker between a phosphonoalkyl unit and a nucleobase has been widely explored [22][23][24][25][26][27][28] including our achievements. The applicability of a 1,2,3-triazole ring as a replacement of sugar [17][18][19] or nucleobase moieties 17,[19][20][21] as well as an additional linker between a phosphonoalkyl unit and a nucleobase has been widely explored [22][23][24][25][26][27][28] including our achievements.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, antiviral and cytostatic activity of ω-(1H-1,2,3-triazol-1-yl)(polyhydroxy)alkylphosphonates as acyclic nucleotide analogues

Głowacka

Balzarini

Andrei

et al. 2014

Bioorganic & Medicinal Chemistry

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The efficient synthesis of a new series of polyhydroxylated dibenzyl ω-(1H-1,2,3-triazol-1-yl)alkylphosphonates as acyclic nucleotide analogues is described starting from dibenzyl ω-azido(polyhydroxy)alkylphosphonates and selected alkynes under microwave irradiation. Selected O,O-dibenzylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses and for cytostatic activity against murine leukemia L1210, human T-lymphocyte CEM and human cervix carcinoma HeLa cells. Compound (1S,2S)-16b exhibited antiviral activity against Influenza A H3N2 subtype (EC50=20μM-visual CPE score; EC50=18μM-MTS method; MCC >100μM, CC50 >100μM) in Madin Darby canine kidney cell cultures (MDCK), and (1S,2S)-16k was active against vesicular stomatitis virus and respiratory syncytial virus in HeLa cells (EC50=9 and 12μM, respectively). Moreover, compound (1R,2S)-16l showed activity against both herpes simplex viruses (HSV-1, HSV-2) in HEL cell cultures (EC50=2.9 and 4μM, respectively) and feline herpes virus in CRFK cells (EC50=4μM) but at the same time it exhibited cytotoxicity toward uninfected cell (MCC⩾4μM). Several other compounds have been found to inhibit proliferation of L1210, CEM as well as HeLa cells with IC50 in the 4-50μM range. Among them compounds (1S,2S)- and (1R,2S)-16l were the most active (IC50 in the 4-7μM range).

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Section: Introductionmentioning

confidence: 99%

Design, synthesis, antiviral and cytostatic activity of ω-(1H-1,2,3-triazol-1-yl)(polyhydroxy)alkylphosphonates as acyclic nucleotide analogues

Głowacka

Balzarini

Andrei

et al. 2014

Bioorganic & Medicinal Chemistry

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“…20. Diethyl 3-{4-[(1,3-dimethyl-2,6-dioxopurin-7-yl)methyl]-1H-1,2,3-triazol-1-yl}propylphosphonate 22i.…”

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The synthesis, antiviral, cytostatic and cytotoxic evaluation of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker

Głowacka

Balzarini

Wróblewski

2013

European Journal of Medicinal Chemistry

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The efficient synthesis of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker is described starting from diethyl azidomethyl-, 2-azidoethyl-, 3-azidopropyl-, 4-azidobutyl-, 2-azido-1-hydroxyethyl-, 3-azido-2-hydroxypropyl- and 3-azido-1-hydroxypropylphosphonates and selected alkynes under microwave irradiation. Several O,O-diethylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses and cytostatic activity against murine leukaemia L1210, human T-lymphocyte CEM and human cervix carcinoma HeLa cells. Acyclonucleotide 22e exhibited activity against both herpes simplex viruses (HSV-1, HSV-2) in HEL cell cultures (EC₅₀ = 17 μM) and feline herpes virus (EC₅₀ = 24 μM) in CRFK cell cultures, while compounds 20k, 21k, 22k and 23k preferentially inhibited proliferation of human T-lymphocyte CEM cells at IC₅₀ in the 2.8-12 μM range.

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“…Detectable amounts of the isomeric products 13 and 14 (total 13–14 %) were isolated only for the small and highly active methyl iodide (Scheme ). The regiochemistry of the substitution was unambiguously determined through a combination of NMR spectroscopy experiments involving 1 H– 1 H NOESY, 1 H– 19 F HOESY, and 1 H– 15 N HMBC (see Scheme and Supporting Information) . Thus, isomer 13 showed a Me–Ar cross‐peak in its 1 H– 1 H NOESY spectrum and two 1 H– 15 N HMBC interactions (Me–N1 and Me–N2).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Regioselective N‐2 Functionalization of 4‐Fluoro‐5‐aryl‐1,2,3‐NH‐triazoles

et al. 2017

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A new efficient synthetic route to 4‐fluoro‐5‐aryl‐1,2,3‐NH‐triazoles was elaborated. The reactions of NaN3 with aryl‐substituted α‐fluoronitroalkenes resulted in the domino construction of the target fluorinated triazoles. Sulfamic acid is an effective promoter for this heterocyclization. The subsequent functionalization reactions of the obtained triazoles proceed highly regioselectively at the N‐2 position. The observed regioselectivity was supported by DFT calculations.

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Synthesis of 1,2,3-triazolo-nucleosides via the post-triazole N-alkylation

Cited by 21 publications

References 92 publications

Design, synthesis, antiviral and cytostatic activity of ω-(1H-1,2,3-triazol-1-yl)(polyhydroxy)alkylphosphonates as acyclic nucleotide analogues

Design, synthesis, antiviral and cytostatic activity of ω-(1H-1,2,3-triazol-1-yl)(polyhydroxy)alkylphosphonates as acyclic nucleotide analogues

The synthesis, antiviral, cytostatic and cytotoxic evaluation of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker

Synthesis and Regioselective N‐2 Functionalization of 4‐Fluoro‐5‐aryl‐1,2,3‐NH‐triazoles

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