1956-30-5Relevant academic research and scientific papers
Synthesis and Antiviral Activity of 5-Thien-2-yl-2'-deoxyuridine Analogues
Wigerinck, Piet,Kerremans, Luc,Claes, Paul,Snoeck, Robert,Maudgal, Prabhat,et al.
, p. 538 - 543 (1993)
A number of 5-heteroaromatic-substituted 2'-deoxyuridines were synthesized from 5-iodo-2'-deoxyuridine using tetraorganotin reagents and palladium complexes as catalyst.The palladium-catalyzed cross-coupling reaction between 5-iodo-2'-deoxyuridine and stannylated heteroaromatics was optimized for the synthesis of the 5-thien-3-yl-2'-deoxyuridine and 5-furan-3-yl-2'-deoxyuridine. 5-(5-Iodothien-2-yl)-2'-deoxyuridine was used as starting material for the synthesis of 5-(5-methylthien-2-yl)-2'-deoxyuridine, 5-(5-vinylthien-2-yl)-2'-deoxyuridine, and 5-(5-ethynylthien-2-yl)-2'-deoxyuridine. 5-(5-Nitrothien-2-yl)-2'-deoxyuridine was synthesized using ceric ammonium nitrate as reagent. 5-(Isoxazol-5-yl)-2'-deoxyuridine was synthesized from 5-(3-oxopropyn-1-yl)-2'-deoxyuridine.Finally, 5-(5-chlorothien-2-yl)-β-D-arabinofuranosyluracil and 5-(5-bromothien-2-yl)-β-D-arabinofuranosyluracil were obtained by halogenation of 5-thien-2-yl-β-D-arabinofuranosyluracil.Introduction of an alkyl substitutent in the 5-position of the thienyl group of 5-thien-2-yl-2'-deoxyuridine or substitution of the 2-deoxyribofuranose ring by an arabinofuranose moiety gave decreased activity against HSV-1 and VZV replication when compared with the 5''-halogenated-5-thien-2-yl-2'-deoxyuridines. 5-(5-Bromothien-2-yl)-2'-deoxyuridine caused prompt healing of HSV-1 keratitis when administered as eye drops (0.2percent) to rabbits.
NMR conformational analysis of p-tolyl furanopyrimidine 2′-deoxyribonucleoside and crystal structure of its 3′,5′-di- O-acetyl derivative
Esho, Noor,Desaulniers, Jean-Paul,Davies, Brian,Chui, Helen M.-P.,Rao, Meneni Srinivasa,Chow, Christine S.,Szafert, Slawomir,Dembinski, Roman
, p. 1231 - 1238 (2005)
The conformation of a representative molecule of a new, potent class of antiviral-active modified nucleosides is determined. A bicyclic nucleoside, 3-(2′-deoxy-β-d-ribofuranosyl)-6-(4-methylphenyl)-2,3-dihydrofuro[2, 3-d]pyrimidin-2-one, shows C2′-endo and C3′-endo ribose conformations in solution (63:37, 37°C; DMSO-d6), as determined by 1H NMR studies. The crystal structure of a 3′,5′-di-O- acetyl-protected derivative (monoclinic, P21, a/b/c = 6.666(1)/12.225(1)/24.676(2) A, β = 90.24(1)°, Z = 4) shows exclusively C2′-endo deoxyribose puckering. The base is found in the anti position both in solution and in crystalline form.
Radiosynthesis of the anticancer nucleoside analogue Trifluridine using an automated 18F-trifluoromethylation procedure
King, Alice,Doepner, Andreas,Turton, David,Ciobota, Daniela M.,Da Pieve, Chiara,Wong Te Fong, Anne-Christine,Kramer-Marek, Gabriela,Chung, Yuen-Li,Smith, Graham
, p. 2986 - 2996 (2018)
Trifluoromethyl groups are widespread in medicinal chemistry, yet there are limited 18F-radiochemistry techniques available for the production of the complementary PET agents. Herein, we report the first radiosynthesis of the anticancer nucleoside analogue trifluridine, using a fully automated, clinically-applicable 18F-trifluoromethylation procedure. [18F]Trifluridine was obtained after two synthetic steps in 99%, and a molar activity of 0.4 GBq μmol-1 ± 0.05. Biodistribution and PET-imaging data using HCT116 tumour-bearing mice showed a 2.5 %ID g-1 tumour uptake of [18F]trifluridine at 60 minutes post-injection, with bone uptake becoming a prominent feature thereafter. In vivo metabolite analysis of selected tissues revealed the presence of the original radiolabelled nucleoside analogue, together with deglycosylated and phosphorylated [18F]trifluridine as the main metabolites. Our findings suggest a potential role for [18F]trifluridine as a PET radiotracer for elucidation of drug mechanism of action.
5-Iodo-4-thio-2′-deoxyuridine: Synthesis, structure, and cytotoxic activity
Zhang, Xiao-Hui,Yin, Hong-Yan,Trigiante, Giuseppe,Brem, Reto,Karran, Peter,Pitak, Mateusz B.,Coles, Simon J.,Xu, Yao-Zhong
, p. 147 - 149 (2015)
The novel nucleoside 5-iodo-4-thio-2′-deoxyuridine (4) was synthesized and fully characterized by IR, NMR, and MS. Its structure was determined by single-crystal X-ray diffraction. Compound 4 absorbs strongly at 346 nm and is minimally toxic to human tumour cells, but its cytotoxicity is substantially enhanced by low dose UVA radiation. The combined use of 4 and UVA offers a promising route to selectively and effectively kill proliferating cells.
Synthesis of C-5 substituted nucleosides via palladium-catalyzed coupling of dienes and amines
Larock, Richard C.,Wang, Yao,Dong, Xiaoyang,Yao, Tuanli
, p. 11427 - 11439 (2005)
The palladium-catalyzed coupling of C-5 iodopyrimidine nucleosides; 1,2-, 1,3-, or 1,ω-dienes; and amines provides a novel and efficient method for the preparation of a wide variety of C-5 aminoalkyl-substituted nucleosides. Adding certain Lewis acids, particularly zinc salts, improves the yields significantly. Secondary amines are the most effective amines for this process. Acyclic and cyclic dienes have been successfully employed. Protection of the 3′- and 5′-hydroxyl groups of iodouridine is required in order to obtain good yields when the coupling process is carried out on 1,3-dienes or long chain or branched non-conjugated dienes.
Design, synthesis, and anticancer activities of novel perfluoroalkyltriazole-appended 2′-deoxyuridines
Park, Sun Min,Yang, Heeju,Park, Song-Kyu,Kim, Hwan Mook,Kim, Byeang Hyean
, p. 5831 - 5834 (2010)
We have focused on the C5-modification of 2′-deoxyuridine with substituted heterocycles for bioactivity, such as antiviral or anticancer activity. Herein, we report a novel class of nucleoside analogues with perfluoroalkyltriazole moiety as an anticancer drug candidate.
Synthesis of carbohydrate-conjugated furo[2,3-d]pyrimidine by 'Click Chemistry'
Jin, Xuanye,Ding, Haixin,Yang, Ruchun,Xiao, Qiang,Ju, Yong
, p. 865 - 870 (2008)
Compounds belonging to a new type of furo[2,3-d]pyrimidine nucleoside conjugated with carbohydrate were synthesized by Sonogashira coupling and 'click chemistry'. Their structures were confirmed on the basis of various types of spectroscopy. Georg Thieme Verlag Stuttgart.
Synthesis and properties of oligonucleotides containing a cholesterol thymidine monomer
Durand, Adeline,Brown, Tom
, p. 785 - 794 (2007)
Highly selective base-pair recognition makes DNA a suitable building block for orderly self-assembled structures. For some applications in nanotechnology DNA complexes need to be fixed onto surfaces. To fulfil this requirement on lipid membranes we have synthesised a thymidine monomer modified with a cholesterol moiety. Solution studies show that the melting temperature (Tm) of the duplex, with adjacent cholesterols on each strand, is much higher than that of the unmodified duplex. Copyright Taylor & Francis Group, LLC.
Mechanism-based inactivation of thymidylate synthase by 5-(3-fluoropropyn-1-yl)-2'-deoxyuridine 5'-phosphate
Kalman, Thomas I.,Nie, Zhe,Kamat, Ashwini
, p. 391 - 394 (2000)
5-Fluoropropynyl-2'-deoxyuridine 5'-phosphate (3) was designed as a mechanism-based inactivator of thymidylate synthase (TS). The inhibitor was synthesized from 5-iodo-2'-deoxyuridine and propargyl alcohol by palladium-catalyzed coupling, followed by fluorination and selective phosphorylation. Incubation of TS with 3, in the presence or absence of the CH2H4folate cofactor, caused rapid, irreversible inactivation of the enzyme. (C) 2000 Elsevier Science Ltd. All rights reserved.
Multicolor live-cell chemical imaging by isotopically edited alkyne vibrational palette
Chen, Zhixing,Paley, Daniel W.,Wei, Lu,Weisman, Andrew L.,Friesner, Richard A.,Nuckolls, Colin,Min, Wei
, p. 8027 - 8033 (2014)
Vibrational imaging such as Raman microscopy is a powerful technique for visualizing a variety of molecules in live cells and tissues with chemical contrast. Going beyond the conventional label-free modality, recent advance of coupling alkyne vibrational tags with stimulated Raman scattering microscopy paves the way for imaging a wide spectrum of alkyne-labeled small biomolecules with superb sensitivity, specificity, resolution, biocompatibility, and minimal perturbation. Unfortunately, the currently available alkyne tag only processes a single vibrational "color", which prohibits multiplex chemical imaging of small molecules in a way that is being routinely practiced in fluorescence microscopy. Herein we develop a three-color vibrational palette of alkyne tags using a 13C-based isotopic editing strategy. We first synthesized 13C isotopologues of EdU, a DNA metabolic reporter, by using the newly developed alkyne cross-metathesis reaction. Consistent with theoretical predictions, the mono-13C (13C≡ 12C) and bis-13C (13C≡13C) labeled alkyne isotopologues display Raman peaks that are red-shifted and spectrally resolved from the originally unlabeled (12C≡ 12C) alkynyl probe. We further demonstrated three-color chemical imaging of nascent DNA, RNA, and newly uptaken fatty-acid in live mammalian cells with a simultaneous treatment of three different isotopically edited alkynyl metabolic reporters. The alkyne vibrational palette presented here thus opens up multicolor imaging of small biomolecules, enlightening a new dimension of chemical imaging.
