75059-22-2Relevant academic research and scientific papers
Synthesis and evaluation of 3′-fluorinated 7-deazapurine nucleosides as antikinetoplastid agents
Bouton, Jakob,Furquim d'Almeida, Arno,Maes, Louis,Caljon, Guy,Van Calenbergh, Serge,Hulpia, Fabian
, (2021/03/06)
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.
Bis 2′-5′-RR-(3′F-A)(3′F-A) cyclic dinucleotide compound and uses thereof
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Page/Page column 114-118, (2021/04/14)
The present invention provides the cyclic dinucleotide compound 2′2′-RR-(3′F-A)(3′F-A) as a highly active immune stimulator that activates DCs via the cytoplasmic receptor known as STING (Stimulator of Interferon Genes), and compositions and uses thereof.
Cyclic dinucleotide compound, preparation method and application thereof
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, (2019/05/11)
The invention discloses a cyclic dinucleotide compound, a preparation method and an application thereof, specifically, the invention relates to a compound of a formula (I), a pharmaceutically acceptable salt thereof, the preparation method thereof, and the application in the preparation of a medicine for treatment and/or prevention of a disease associated with activation of STING protein or as a vaccine adjuvant. The diseases associated with activation of the STING protein include viral infections, bacterial infections, cancers, diseases related to the immune system, and the like.
LOCKED NUCLEIC ACID CYCLIC DINUCLEOTIDE COMPOUNDS AND USES THEREOF
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Paragraph 0559; 0570-0571, (2019/07/03)
The present invention provides highly active locked nucleic acid cyclic-dinucleotide (LNA-CDN) immune stimulators that activate DCs via the cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the LNA-CDNs of the present in
3 the [...] -fluoro-substituted purine nucleoside analogues, its preparation process and its application
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, (2016/10/08)
The invention discloses a nucleoside analog, a preparation method and application thereof, relates to a 3'-fluorine-3'-deoxy-purine substituted nucleoside analog, a preparation method and application thereof, and belongs to the field of medical chemistry.
Synthesis of 3′-fluoro-trna analogues for exploring nonribosomal peptide synthesis in bacteria
Iannazzo, Laura,Laisné, Guillaume,Fonvielle, Matthieu,Braud, Emmanuelle,Herbeuval, Jean-Philippe,Arthur, Michel,Etheve-Quelquejeu, Mélanie
, p. 477 - 486 (2015/02/19)
Aminoacyl-tRNAs (aa-tRNAs) participate in a vast repertoire of metabolic pathways, including the synthesis of the peptidoglycan network in the cell walls of bacterial pathogens. Synthesis of aminoacyl-tRNA analogues is critical for further understanding the mechanisms of these reactions. Here we report the semi-synthesis of 3′-fluoro analogues of Ala-tRNAAla. The presence of fluorine in the 3′-position blocks Ala at the 2′-position by preventing spontaneous migration of the residue between positions 2′ and 3′. NMR analyses showed that substitution of the 3′-hydroxy group by fluorine in the ribo configuration favours the S-type conformation of the furanose ring of terminal adenosine A76. In contrast, the N-type conformation is favoured by the presence of fluorine in the xylo configuration. Thus, introduction of fluorine in the ribo and xylo configurations affects the conformation of the furanose ring in reciprocal ways. These compounds should provide insight into substrate recognition by Fem transferases and the Ala-tRNA synthetases.
Investigation and Conformational Analysis of Fluorinated Nucleoside Antibiotics Targeting Siderophore Biosynthesis
Dawadi, Surendra,Viswanathan, Kishore,Boshoff, Helena I.,Barry, Clifton E.,Aldrich, Courtney C.
, p. 4835 - 4850 (2015/05/27)
(Chemical Equation Presented) Antibiotic resistance represents one of the greatest threats to public health. The adenylation inhibitor 5′-O-[N-(salicyl)sulfamoyl]adenosine (SAL-AMS) is the archetype for a new class of nucleoside antibiotics that target iron acquisition in pathogenic microorganisms and is especially effective against Mycobacterium tuberculosis, the causative agent of tuberculosis. Strategic incorporation of fluorine at the 2′ and 3′ positions of the nucleoside was performed by direct fluorination to enhance activity and improve drug disposition properties. The resulting SAL-AMS analogues were comprehensively assessed for biochemical potency, whole-cell antitubercular activity, and in vivo pharmacokinetic parameters. Conformational analysis suggested a strong preference of fluorinated sugar rings for either a 2′-endo, 3′-exo (South), or a 3′-endo,2′-exo (North) conformation. The structure-activity relationships revealed a strong conformational bias for the C3′-endo conformation to maintain potent biochemical and whole-cell activity, whereas improved pharmacokinetic properties were associated with the C2′-endo conformation.
Aplysia californica mediated cyclisation of novel 3′-modified NAD+ analogues: A role for hydrogen bonding in the recognition of cyclic adenosine 5′-diphosphate ribose
Mort, Christopher J. W.,Migaud, Marie E.,Galione, Antony,Potter, Barry V. L.
, p. 475 - 487 (2007/10/03)
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
Synthesis of 8-substituted analogs of 3'-deoxy-3'-fluoroadenosine
Maruyama, Tokumi,Sato, Yoshiko,Sakamoto, Takeshi
, p. 115 - 122 (2007/10/03)
After 2',5'-di-O-protection of 8-bromoadenosine, the product was converted to the xyloside, which was successively treated with diethylaminosulfur trifluoride (DAST) and acid to afford 8-bromo-3'-deoxy- 3'-fluoroadenosine. 8-Mercapto and 8-oxy analogs wer
Synthesis of 2'-β-Fluoro- and 3'-α-Fluoro-Substituted Guanine Nucleosides. Effects of Sugar Conformational Shifts on Nucleophilic Displacement of the 2'-Hydroxy and 3'-Hydroxy Group with DAST
Pankiewicz, Krzysztof W.,Krezeminski, Jacek,Watanabe, Kyoichi A.
, p. 7315 - 7321 (2007/10/02)
Tritylation of 2-N-acetyl-6-O-((4-nitrophenyl)ethyl)guanosine (4) with TrCl/DMAP followed by TrCl/AgNO3 afforded a mixture of isomeric 3',5'-di-O-trityl and 2',5'-di-O-trityl derivatives 6 and 7, which were separated on a silica gel column to give 6 and 7 in 40percent and 50percent yield, respectively.Upon treatment with DAST, 6 was converted into the corresponding 2'-β-fluoro nucleoside 8 in 43percent yield.Deprotection of the 2-N-acetyl group occurred during the reaction.Removal of the 6-O-NPE group from 8 with DBU/pyridine, followed by detritylation with CF3COOH/CHCl3, gave F-ara-G (1b) in good yield.The same treatment of 7 with DAST did not lead to nucleophilic substitution with fluoride ion, but only decomposition took place.Treatment of the 2',5'-di-O-trityl nucleoside 7 with CF3SO2Cl/DMAP in CH2Cl2, followed by PhCO2K/HMPA, afforded the corresponding xylofuranosyl derivative 16 along with 6-O-deprotected nucleoside 19.The 6-O-NPE group was completely removed in the reaction of triflate nucleoside 15 with CH3CO2Na/HMPA.The obtained diacetyl nucleoside 20 under hydrolysis with Et3N/MeOH/H2O gave 9-(2,5-di-O-trityl-β-D-xylofuranosyl)guanine (22).Upon reaction of derivative 22 with DAST no formation of the desired 3'-fluoro nucleoside 23 was observed, but only decomposition took place.When, however, the triflate nucleoside 15 was treated with CH3COONa in DMF instead of HMPA the corresponding diacetyl nucleoside 17 with intact 6-O-NPE group was obtained.This compound was hydrolyzed with Et3N/MeOH/H2O to give the 2-N-acetyl derivative 18, which was smoothly converted into the desired 3'-α-fluoro-substituted nucleoside 24 in 76percent yield.Again, removal of the 2-N-acetyl group occured during the reaction with DAST.Compound 24 was deprotected with DBU/pyridine followed by CF3COOH/CHCl3 to give 3'-fluoro-3'-deoxyguanosine in good yield (3b).In a similar manner the O2,O5,N6-tritrityladenosine (25) was converted into the corresponding 3'-deoxy-3'-fluoroadenosine (3a).
