55612-11-8Relevant articles and documents
Optimized synthesis of 3′-O-aminothymidine and evaluation of its oxime derivative as an anti-HIV agent
Solyev, Pavel N.,Jasko, Maxim V.,Martynova, Tatiana A.,Kalnina, Ludmila B.,Nosik, Dmitry N.,Kukhanova, Marina K.
, p. 291 - 295 (2015/10/28)
The synthesis and isolation of 3′-O-aminothymidine oximes have been optimized. Synthesized compounds were characterized by NMR and UV spectral and analytical data. A mixture of previously not reported syn and anti isomers of acetaldoximes was assessed for anti-HIV activity and the prevention of syncytia formation caused by HIV-1 infection.
Antiviral activity of various 1-(2′-Deoxy-β- d -lyxofuranosyl), 1-(2′-Fluoro-β- d -xylofuranosyl), 1-(3′-Fluoro-β- d -arabinofuranosyl), and 2′-fluoro-2′,3′-didehydro-2′, 3′-dideoxyribose pyrimidine nucleoside analogues against duck hepatitis B virus (DHBV) and human hepatitis B virus (HBV) replication
Srivastav, Naveen C.,Shakya, Neeraj,Mak, Michelle,Agrawal, Babita,Tyrrell, D. Lorne,Kumar, Rakesh
experimental part, p. 7156 - 7166 (2010/12/19)
Despite the existence of successful vaccine and antiviral therapies, infection with hepatitis B virus (HBV) continues to be a major global cause of acute and chronic liver disease and high mortality. We synthesized and evaluated several lyxofuranosyl, 2′-fluoroxylofuranosyl, 3′- fluoroarabinofuranosyl, and 2′-fluoro-2′,3′-didehydro- 2′,3′-dideoxyribose pyrimidine nucleoside analogues for antiviral activities against hepatitis B virus. Among the compounds examined, 1-(2-deoxy-β-d-lyxofuranosyl)thymine (23), 1-(2-deoxy-β-d- lyxofuranosyl)-5-trifluoromethyluracil (25), 1-(2-deoxy-2-fluoro-β-d- xylofuranosyl)uracil (38), 1-(2-deoxy-2-fluoro-β-d-xylofuranosyl)thymine (39), 2′,3′-dideoxy-2′,3′-didehydro-2′- fluorothymidine (48), and 2′,3′-dideoxy-2′,3′-didehydro- 2′-fluoro-5-ethyluridine (49) were found to possess significant anti-HBV activity against DHBV in primary duck hepatocytes with EC50 values of 4.1, 3.3, 40.6, 3.8, 0.2, and 39.0 μM, respectively. Compounds 23, 25, 39, 48, and 49 (EC50 = 41.3, 33.7, 19.2, 2.0-4.1, and 39.0 μM, respectively) exhibited significant activity against wild-type human HBV in 2.2.15 cells. Intriguingly, 25, 39, 48, and 49 retained sensitivity against lamivudine-resistant HBV containing a single mutation (M204I) and 48 emerged as an effective inhibitor of drug-resistant HBV with an EC50 of 4.1 μM. In contrast, 50% inhibition could not be achieved by lamivudine at 44 μM concentration in the drug-resistant strain. The compounds investigated did not show cytotoxicity to host cells up to the highest concentrations tested.
Method for sequencing DNA and RNA by synthesis
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Page/Page column 12, (2009/06/27)
This invention relates to the field of nucleic acid chemistry, more specifically to the field of compositions and processes that are nucleic acid analogs. More specifically, this invention relates to compositions that allow the sequencing of oligonucleotides by synthesis, and processes for sequencing by synthesis that exploit these compositions. Most specifically, the instant invention discloses compositions of matter that are 5′-triphosphates of ribo- and 2′-deoxyribonucleosides wherein the 3′-OH group is replaced by a 3′-ONHR group in the alpha configuration, wherein R is either a H or CH3 group. Also disclosed are these triphosphates where the nucleobase carries, via a linker, a reporter groups, such as a fluorescent species that can be used in single- or multi-copy DNA sequencing, or a tag that can be visualized by ultramicroscopy. Also disclosed are processes that use these compositions to do sequencing by synthesis.
Synthesis and Antiviral Activity of Novel Fluorinated 2′,3′ -Dideoxynucleosides
Kumar, Piyush,Ohkura, Kazue,Balzarini, Jan,De Clercq, Erik,Seki, Koh-Ichi,Wiebe, Leonard I.
, p. 7 - 29 (2007/10/03)
A series of 5-(trifluoroethoxymethyl)-2′,3′-dideoxyuridines and 5-[bis(trifluormethoxy)-methyl]-2′,3′-dideoxyuridines have been prepared and screened for antiviral activity. The conformations of these compounds are discussed on the bases of NOE studies and the MO calculations. Modelling and NOE studies suggest both syn- and anti conformations for these 5-(2,2,2-trifluoroethoxymethyl)- and 5-[bis(2,2,2-trifluoroethoxy)-methyl]-derivatives. The NOE parameters are also suggested to be more attributable to the nature of the fluorine atom than to structural or conformational changes. Compounds 17, 26 and 30 showed some activity in anti-HIV-1 and anti-HIV-2 assays, but the compounds were devoid of activity against HSV and human rhinovirus. The compounds tested exhibited low cytotoxicity and were inactive against a bank of cancer cells in vitro.
Synthesis and evaluation of thymidine-5′-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase
Vanheusden, Veerle,Munier-Lehmann, Helene,Pochet, Sylvie,Herdewijn, Piet,Van Calenbergh, Serge
, p. 2695 - 2698 (2007/10/03)
A number of 2′- and 3′-modified thymidine 5′-O-monophosphate analogues were synthesized as potential leads for new anti-mycobacterial drugs. Evaluation of their affinity for Mycobacterium tuberculosis thymidine monophosphate kinase showed that a 2′-halogeno substituent and a 3′-azido function are the most favorable leads for further development of potent inhibitors of this enzyme.
Stereocontrolled synthesis of β-2'-deoxypyrimidine nucleosides via intramolecular glycosylations
Xia, Xiaoyang,Wang, Jianying,Hager, Michael W.,Sisti, Nicholas,Liotta, Dennis C.
, p. 1111 - 1114 (2007/10/03)
A pyrimidine moiety was tethered at the 3'-β-position of D-threo-furanosides. By carefully controlling the reaction conditions, pyrimidine bases can be delivered to the anomeric center to give of β-pyrimidine nucleosides in good yield and with complete stereocontrol.
Synthesis of 3'-Fluoromethylthio-, 3'-Fluoromethylsulfinyl- and 3'-Fluoromethylsulfonyl-substituted 3'-Deoxythymidine
Herdewijn, Piet,Bruyn, Andre De,Wigerinck, Piet,Hendrix, Chris,Kerremans, Luk,et al.
, p. 249 - 256 (2007/10/02)
3'-Deoxy-3'-(fluoromethylthio)thymidine 2 is synthesized from 5'-O-benzoyl-3'-deoxy-3'-(methylsulfinyl)thymidine 9 by using DAST. 5'-O-Benzoyl-3'-deoxy-3'-(fluoromethylthio)thymidine is used as starting material for the synthesis of the sulfoxide 3 and the sulfone 4.Both sulfoxides 3A and 3B show a C3'-endo sugar conformation.
Synthesis of 1-(3'-azido-2',3'-dideoxy-α-L-threo-pentofuranosyl)thymine as a potential anti-HIV agent
Czernecki,Le Diguarher
, p. 683 - 686 (2007/10/02)
Starting from methyl 2,3,5-tri-O-benzoyl-α-L-arabinofuranoside, a multistep synthesis of the C-4' epimer of AZT is described. Glycosylation of silylated thymine with 2,3,5-tri-O-benzoyl-L-arabinofuranosyl acetate (5) affords the α-nucleoside 7 after debenzoylation. Deoxygenation at C-2' of the selectively protected 8, followed by displacement of a 3'-methanesulfonyl group by lithium azide leads to the title compound which did not exhibit antiviral activity against HIV-1.
Synthesis of 3'-fluoro-3'-deoxythymidine and studies of its 18F-radiolabeling, as a tracer for the noninvasive monitoring of the biodistribution of drugs against AIDS
Wilson, I. K.,Chatterjee, S.,Wolf, W.
, p. 283 - 289 (2007/10/02)
3'-Fluoro-3'-deoxy-thymidine (FDT), a fluorinated analog of 3'-azido-thymidine (AZT), is both more active against the HIV virus but also more toxic than AZT.Because of its fluorine atom, it can be labeled with 18F to be used to monitor this drug's biodistribution and targeting.A new synthesis for FDT, suited for 18F labeling, has been developed.After protecting the 5'-hydroxy group with a trityl group, the 3'-hydroxy group was substituted with a mesyl group in the lyxo configuration.Treatment with 18F potassium fluoride and crown-18 ether yielded the 18F-labeled fluoro derivative which on detritylation afforded 18F FDT with 7percent labeling efficiency.This is the first reported synthesis of 3'-fluoro-5'-O-trityl deoxythymidine using potassium fluoride and preparing its 18F labeled analog.The time required to incorporate 18F in the intermediate compound and isolate the end-product is reasonably short (approximately 2 h) which will allow sufficient time to conduct biological studies with this short-lived radionuclide.
