83159-91-5Relevant articles and documents
Synthesis and anti-HCV activity of a series of β-D-2′-deoxy-2′-dibromo nucleosides and their corresponding phosphoramidate prodrugs
Chen, Zhe,Cox, Bryan D.,Garnier-Amblard, Ethel C.,McBrayer, Tamara R.,Coats, Steven J.,Schinazi, Raymond F.,Amblard, Franck
, p. 5296 - 5299 (2017)
Several β-D-2′-deoxy-2′-substituted nucleoside analogs have displayed potent and selective anti-HCV activities and some of them have reached human clinical trials. In that regard, we report herein the synthesis of a series of 2′-deoxy,2′-dibromo substituted U, C, G and A nucleosides 10a–d and their corresponding phosphoramidate prodrugs 13a–d. The synthesized nucleosides 10a–d and prodrugs 13a–d were evaluated for their inhibitory activity against HCV as well as cellular toxicity. The results showed that the most potent compound was prodrug 13a, which exhibited micromolar inhibitory activity (EC50 = 1.5 ± 0.8 μM) with no observed toxicity. In addition, molecular modeling and free energy perturbation calculations for the 5′-triphosphate formed from 13a and related 2′-modified nucleotides are discussed.
Synthesis of isomeric analogues of S-ribosylhomocysteine analogues with homocysteine unit attached to C2 of ribose
Chbib, Christiane
supporting information, p. 1681 - 1685 (2017/04/04)
LuxS (S-ribosylhomocysteinase; EC 4.4.1.21) is an enzyme that catalyzes the cleavage of the thioether linkage in the catalytic pathway of S-ribosylhomocysteine (SRH) which produces homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD). DPD is the precursor of the signaling molecules known as autoinducer 2 (AI-2) responsible for the bacterial quorum sensing (QS) identified as cell to cell communication. Inhibitors of LuxS should be able to interfere with its catalytic pathway thus preventing the formation of the autoinducer molecules. In this work, the synthesis of 2-deoxy-2-bromo-SRH analogues was attempted by the coupling of the corresponding 2-bromo-2-deoxypentafuranosyl sugars with the homocysteinate anion. The displacement of the bromide from C2 rather than the expected substitution of the mesylate group from C5 was observed leading to a novel isomeric analogue of SRH in which Hcy moiety is attached to a ribose ring via C2-sulfur bond.
2'-DICHLORO AND 2'-FLUORO-2'-CHLORO NUCLEOSIDE ANALOGUES FOR HCV INFECTION
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Paragraph 00292, (2015/06/11)
Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2'-dichloro or 2'-fluoro-2'-chloro nucleoside analogue compounds which display remarkable efficacy and bioavailability for the treatment of, for example, HCV infection in a human. In certain embodiments, the compounds are of Formula (I):or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof; wherein each of RA and RB is independently Cl or F, wherein at least one of RA and RB is C1; and Base, PD and Z are as described herein.
