- Synthesis and evaluation of 3′-fluorinated 7-deazapurine nucleosides as antikinetoplastid agents
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Kinetoplastid parasites are the causative agents of neglected tropical diseases with an unmet medical need. These parasites are unable to synthesize the purine ring de novo, and therefore rely on purine salvage to meet their purine demand. Evaluating purine nucleoside analogs is therefore an attractive strategy to identify antikinetoplastid agents. Several anti-Trypanosoma cruzi and anti-Trypanosoma brucei 7-deazapurine nucleosides were previously discovered, with the removal of the 3′-hydroxyl group resulting in a significant boost in activity. In this work we therefore decided to assess the effect of the introduction of a 3′-fluoro substituent in 7-deazapurine nucleosides on the anti-kinetoplastid activities. Hence, we synthesized two series of 3′-deoxy-3′-fluororibofuranosyl and 3′-deoxy-3′-fluoroxylofuranosyl nucleosides comprising 7-deazaadenine and -hypoxanthine bases and assayed these for antiparasitic activity. Several analogs with potent activity against T. cruzi and T. brucei were discovered, indicating that a fluorine atom in the 3′-position is a promising modification for the discovery of antiparasitic nucleosides.
- Bouton, Jakob,Caljon, Guy,Furquim d'Almeida, Arno,Hulpia, Fabian,Maes, Louis,Van Calenbergh, Serge
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- Phosphoramidate derivatives of nucleoside compounds and uses of derivatives
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The invention belongs to the technical field of medicines, and relates to phosphoramidate derivatives of nucleoside compounds, uses of the phosphoramidate derivatives, and a pharmaceutical compositioncontaining the compounds. The derivatives and pharmaceu
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Paragraph 0166; 0193-0197
(2020/12/14)
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- Studies on the synthesis of nicotinamide nucleoside and nucleotide analogues and their inhibitions towards CD38 nadase
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Nicotinamide adenine dinucleotide (NAD) analogues inhibit the NADase activity of CD38. In the current study, efficient protocols for the synthesis of substituted-nicotinamide nucleosides and nucleotides were developed. The one-pot phosphorylation-esterification strategy provides a convenient way of obtaining nicotinamide nucleoside phosphodiesters from the corresponding nucleosides. Structure-activity relationship information revealed that replacement of 3'-hydroxy group with F or N3 led to the considerably decrease of activity as compared with ara-F NMN. Phosphodiesterification of nicotinamide nucleosides lowers their inhibitory activities in some extent.
- Chen, Zhe,Kwong, Anna Ka Yee,Yang, Zhenjun,Zhang, Liangren,Lee, Hon Cheung,Zhang, Lihe
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experimental part
p. 2837 - 2850
(2012/02/13)
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- Aplysia californica mediated cyclisation of novel 3′-modified NAD+ analogues: A role for hydrogen bonding in the recognition of cyclic adenosine 5′-diphosphate ribose
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Cyclic ADP-ribose mobilizes intracellular Ca2+ in a variety of cells. To elucidate the nature of the interaction between the C3′ substituent of cADP-ribose and the cADPR receptor, three analogues of NAD + modified in the adenosine ri
- Mort, Christopher J. W.,Migaud, Marie E.,Galione, Antony,Potter, Barry V. L.
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p. 475 - 487
(2007/10/03)
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- Synthesis of a 2,3-dideoxy-2,3-difluorofuranose with the D-lyxo configuration. An intramolecular rearrangement of methyl 5-O-benzoyl-2,3-dideoxy-2,3-difluoro-D-lyxofuranoside observed during the attempted synthesis of 1-(2,3-dideoxy-2,3-difluoro-β-D-lyxof
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A new sugar, methyl 5-O-benzoyl-2,3-dideoxy-2,3-difluoro-D-lyxofuranoside (8), which features fluorine substituents on adjacent carbon positions above the plane of the tetrahydrofuran ring, was synthesized from 1,2:5,6-di-O-isopropylidene-α-D-allofuranose
- Jeong,Lim,Marquez
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p. 103 - 114
(2007/10/02)
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- 1,2-Di-O-acetyl-5-O-benzoyl-3-deoxy-3-fluoro-D-xylofuranose. A versatile precursor for the synthesis of 3-deoxy-3-fluoro-β-D-xylofuranosyl nucleosides as potential antiviral agents
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The title compound has been synthesized from D-xylose for use in the preparation of 3-deoxy-3-fluoro-β-D-xylofuranosyl nucleoside analogues and their 2-deoxy derivatives, as exemplified in the guanine and thymine series. The title compound has been synthe
- Gosselin,Puech,Genu-Dellac,Imbach
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- SYNTHESIS OF 9-(3-DEOXY- AND 2,3-DIDEOXY-3-FLUORO-β-D-XYLOFURANOSYL)GUANINES AS POTENTIAL ANTIVIRAL AGENTS
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The first synthesis of the title compounds 8 and 10 was accomplished by a multi-step approach involving prior preparation of a suitably protected fluorosugar 6.
- Puech, Frederic,Gosselin, Gilles,Imbach, Jean-Louis
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p. 3171 - 3174
(2007/10/02)
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