Fluorinated Nucleosides as Antiviral and Antitumor Agents

Meng, Weidong; Qing, Feng‐Ling

doi:10.2174/156802606777951082

Cited by 69 publications

(33 citation statements)

References 49 publications

(60 reference statements)

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“…The crystal structures that were completely optimized using Gaussian 98 28 were used as starting points. Constrained optimizations (endocyclic torsion angles ν 0 and either ν 3 or ν 4 were held fixed to maintain conformations with desired values of P and ν max ) were carried out first in a semiempirical mode using AM1 followed by ab initio optimizations similar as described in the Computational Methods section above (RHF/6-31G* ⇒ B3LYP/6-31G* ⇒ B3LYP/6-311++G**). These calculations were repeated with the ν max fixed at 38° to compare to data sets with ν max values that are typical of standard nucleosides.…”

Section: Determination Of Coefficients a And Bmentioning

confidence: 99%

Comprehensive Structural Studies of 2′,3′-Difluorinated Nucleosides: Comparison of Theory, Solution, and Solid State

et al. 2008

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The conformations of three 2′,3′-difluoro uridine nucleosides were studied by X-ray crystallography, NMR spectroscopy, and ab initio calculations in an attempt to define the roles that the two vicinal fluorine atoms play in the puckering preferences of the furanose ring. Two of the compounds examined contained fluorine atoms in either the arabino or xylo dispositions at C2′ and C3′ of a 2′, 3′-dideoxyuridine system. The third compound also incorporated fluorine atoms in the xylo configuration on the furanose ring but was substituted with a 6-azauracil base in place of uracil. A battery of NMR experiments in D 2 O solution was used to identify conformational preferences primarily from coupling constant and NOE data. Both 1 H and 19 F NMR data were used to ascertain the preferred sugar pucker of the furanose ring through the use of the program PSEUROT. Compound-dependent parameters used in the PSEUROT calculations were newly derived from complete sets of conformations calculated from high-level ab initio methods. The solution and theoretical data were compared to the conformations of each molecule in the solid state. It was shown that both gauche and antiperiplanar effects may be operative to maintain a pseudodiaxial arrangement of the C2′and C3′ vicinal fluorine atoms. These data, along with previously reported data by us and others concerning monofluorinated nucleoside conformations, were used to propose a model of how fluorine influences different aspects of nucleoside conformations.

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Section: Determination Of Coefficients a And Bmentioning

confidence: 99%

Comprehensive Structural Studies of 2′,3′-Difluorinated Nucleosides: Comparison of Theory, Solution, and Solid State

et al. 2008

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“…A variety of strategies have been devised to design nucleoside analogues, involving several structural modifications on the sugar moiety of naturally occurring nucleosides [7]. Consequently, over the past two decades, extensive work has been conducted to search for new types of nucleosides with high activity and less toxicity, and those that are less prone to trigger drug resistance [8].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Antiviral and Cytostatic Evaluation of Unsaturated Exomethylene and Keto D‐Lyxopyranonucleoside Analogues

Tzioumaki¹,

Tsoukala²,

Manta³

et al. 2009

Archiv der Pharmazie

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This report describes the synthesis of unsaturated exomethylene lyxopyranonucleoside analogues as potential biologically active agents. Commercially available 1,2,3,4-tetra-O-acetyl-alpha-D-lyxopyranose 1 was condensed with silylated thymine and uracil, respectively, deacetylated and acetalated to afford 1-(2,3-O-isopropylidene-alpha-D-lyxopyranosyl)thymine 4a and 1-(2,3-O-isopropylidene-alpha-D-lyxopyranosyl)uracil 4b. The new derivatives 1-(2,3,4-trideoxy-4-methylene-alpha-pent-2-enopyranosyl)thymine 8a and 1-(2,3,4-trideoxy-4-methylene-alpha-pent-2-enopyranosyl)uracil 8b were prepared via two different key intermediates, 7a, b and 13a, b in order to elucidate the influence of 2',3'-unsaturation and to clarify the difference between the keto and exomethylene group on the biological activity of the target molecules. Compounds 7a, b, 8a, b, and 13a, b were evaluated for their antiviral and cytostatic activity using several virus strains and cell lines. Whereas no marked antiviral activity was noticed, 13a and 13b showed a cytostatic activity that ranged between 7 and 23 muM for 13a and 26 and 38 muM for 13b against murine leukemia L1210, human lymphocyte Molt4/C8 and CEM cells, and human breast carcinoma MCF7 cells.

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“…For example, fluorinated nucleosides are prevalent among inhibitors of human immunodeficiency viruses. [1] The electrophile-induced cyclization of fluorinated precursors has emerged as a suitable route to prepare these heterocycles. This strategy was applied successfully to homoallylic fluorides for the preparation of diverse a-fluoro-iodolactones.…”

Section: In Memory Of Charles Mioskowskimentioning

confidence: 99%

Fluorine‐Directed Diastereoselective Iodocyclizations

et al. 2007

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Fluorinated Nucleosides as Antiviral and Antitumor Agents

Abstract: The synthesis of nucleosides and analogues with fluoride modifications on the surgar moiety are reviewed, and their biological activities as potential antiviral and anti-tumor agents are also discussed.

Cited by 69 publications

References 49 publications

Comprehensive Structural Studies of 2′,3′-Difluorinated Nucleosides: Comparison of Theory, Solution, and Solid State

Comprehensive Structural Studies of 2′,3′-Difluorinated Nucleosides: Comparison of Theory, Solution, and Solid State

Synthesis, Antiviral and Cytostatic Evaluation of Unsaturated Exomethylene and Keto D‐Lyxopyranonucleoside Analogues

Fluorine‐Directed Diastereoselective Iodocyclizations

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