123606-62-2Relevant academic research and scientific papers
Independent generation and study of 5,6-dihydro-2′-deoxyuridin-6-yl, a member of the major family of reactive intermediates formed in DNA from the effects of γ-radiolysis
Carter, K. Nolan,Greenberg, Marc M.
, p. 4275 - 4280 (2003)
Nucleobase radicals are the major family of reactive intermediates formed when nucleic acids are exposed to γ-radiolysis. Elucidation of their reactivity is complicated by the formation of multiple species randomly throughout the biopolymers. 5,6-Dihydro-2′-deoxyuridin-6-yl (1) was generated upon photolysis (350 nm) of the respective tert-butyl ketone (2). The radical abstracts hydrogen atoms from β-mercaptoethanol (k = 8.8 ± 0.5 × 106 M-1 s-1) and 2,5-dimethyltetrahydrofuran (k = 31 ± 2.5 M-1 s-1). The latter was used as a model for the 2-deoxyribose component of DNA. The major product formed in the presence of O2 was 6-hydroxy-5,6-dihydro-2′-deoxyuridine (11), which is believed to be formed directly from the peroxy precursor and not via elimination of superoxide. Small amounts of 2-deoxyribonolactone (13) were also formed under aerobic conditions. This product is believed to result from intramolecular hydrogen atom abstraction by the C6-peroxyl radical (14) and suggests that γ-radiolysis may indirectly result in oxidation of the C1′-position of nucleotides, despite the inaccessibility of this hydrogen in duplex DNA.
In search of flavivirus inhibitors: Evaluation of different tritylated nucleoside analogues
Chatelain, Grégory,Debing, Yannick,De Burghgraeve, Tine,Zmurko, Joanna,Saudi, Milind,Rozenski, Jef,Neyts, Johan,Van Aerschot, Arthur
supporting information, p. 249 - 255 (2013/10/01)
Following up on a hit that was identified in a large scale cell-based antiviral screening effort, a series of triphenylmethyl alkylated nucleoside analogues were synthesized and evaluated for their in vitro antiviral activities against the dengue virus (DENV) and the yellow fever virus (YFV). Hereto, trityl moieties were attached at various positions of the sugar ring combined with subtle variations of the heterocyclic base. Several triphenylmethyl modified nucleosides were uncovered being endowed with submicromolar in vitro antiviral activity against the YFV. The most selective inhibitor in this series was 3′,5′-bis-O-tritylated-5-chlorouridine (1b) affording a selectivity index of over 90, whereas the 3′,5′-bis-O-tritylated inosine congener (5b) displayed the highest activity, but proved more toxic. The finding of these lipophilic structures being endowed with high antiviral activity for flaviviruses, should stimulate the interest for further structureeactivity research.
Deoxyuridine triphosphate nucleotidohydrolase as a potential antiparasitic drug target
Nguyen, Corinne,Kasinathan, Ganasan,Leal-Cortijo, Isabel,Musso-Buendia, Alexander,Kaiser, Marcel,Brun, Reto,Ruiz-Pérez, Luis M.,Johansson, Nils G.,González-Pacanowska, Dolores,Gilbert, Ian H.
, p. 5942 - 5954 (2007/10/03)
This paper describes a structure-activity study to identify novel, small-molecule inhibitors of the enzyme deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) from parasitic protozoa. The successful synthesis of a variety of analogues of dUMP is de
Selective deprotection of fully benzoylated nucleoside derivatives
Zerrouki, Rachida,Roy, Vincent,Hadj-Bouazza, Amel,Krausz, Pierre
, p. 299 - 303 (2007/10/03)
Selective deprotection of benzoylated hydroxyl groups is one of the crucial problems in the synthesis of nucleoside analogues as well as of other polyfunctional molecules. Copyright
Direct measurement of pyrimidine C6-hydrate stability
Nolan Carter,Greenberg, Marc M.
, p. 2341 - 2346 (2007/10/03)
Pyrimidine C6-hydrates are produced via UV-irradiation and undergo dehydration upon standing. The stability of these compounds has a direct bearing on their genotoxicity. The rate constants for elimination from 5' -benzyoylated derivatives of 5,6-dihydro- 5-hydroxythymidine (6) and 5,6-dihydro-5-hydroxy-2' -deoxyuridine (9) were measured directly via HPLC. The rate constants for dehydration increase from pH 6.0 to 8.0. The half-lives for 6 and 9 at pH 7.4 and 37°C are 46.5 and 24.4 h, respectively. Deglycosylation is not observed, even upon heating at 90°C. These observations reinforce proposals that pyrimidine hydrates are sufficiently long-lived that they can exert significant effects on biological systems. Copyright
Synthesis of 4'-cyanothymidine and analogs as potent inhibitors of HIV
O-Yang,Wu,Fraser-Smith,Walker
, p. 37 - 40 (2007/10/02)
4'-Cyanothymidine inhibits HIV in A301 (Alex) cells with an IC50 of 0.002 μM. The uridine and cytidine analogs show similar potencies.
CONVENIENT SYNTHESIS OF 5'-METHYL-2'-DESOXYURIDINES
Mikhailov, S.N.,Padyukova, N.Sh.,Panov, K.I.
, p. 203 - 205 (2007/10/02)
A convenient method has been developed for the synthesis of 5'-methyl-2'-desoxyuridines.Chlorination of 5'-O-benzoyl-5'-methyluridines with a mixture of Ph3P and CCl4 in DMF affords the 2'-desoxy-2'-chloro-derivatives, which are then reduced with tributyl
