1956-30-5Relevant articles and documents
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.
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.
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.
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.
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.
Extension of furopyrimidine nucleosides with 5-alkynyl substituent: Synthesis, high fluorescence, and antiviral effect in the absence of free ribose hydroxyl groups
Kaczmarek, Renata,Twardy, Dylan J.,Olson, Trevor L.,Korczyński, Dariusz,Andrei, Graciela,Snoeck, Robert,Dolot, Rafa?,Wheeler, Kraig A.,Dembinski, Roman
supporting information, (2020/10/13)
A novel methodology to access alkynyl nucleoside analogues is elaborated. Highly fluorescent 5-alkynylfuropyrimidines were synthesized (97-46%) and their antiviral properties investigated in vitro. Regiochemistry of the functionalization was achieved with the aid of 5-endo-dig electrophilic halocyclization of acetyl 5-p-tolyl- or 5-p-pentylphenyl-2′-deoxyuridine. Structure of one of the resulting nucleosides, 6-p-tolyl-5-iodo-2′-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-one, was confirmed by X-ray crystallography, and its conformation was compared to related nucleosides. Diverse alkynyl substituents were introduced at the heterobicyclic base C-5 position via Sonogashira coupling of 5-iodo-2′-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-ones. The resulting compounds had fluorescence emissions of 452–481 nm. High quantum yields of 0.53–0.60 were observed for 9-ethynyl-9-fluorenol and propargyl alcohol/methyl ether-modified furopyrimidines. These modified nucleosides, designed in the form of ribose acetyl esters, are potential tools for fluorescent tagging, studying nucleoside metabolism, 2′-deoxyribonucleoside kinase activity, and antiviral activity. Antiviral assays against a broad spectrum of DNA and RNA viruses showed that in human embryonic lung (HEL) cell cultures some of the compounds showed antiviral activity (EC50 1.3–13.2 μM) against varicella-zoster virus (VZV). The alkynyl furopyrimidine with two p-pentylphenyl substituents emerged as the best compound with reasonable and selective anti-VZV activity, confirming p-pentylphenyl potency as a pharmacophore.
NMR studies on 4-thio-5-furan-modified and 4-thio-5-thiophene-modified nucleosides
Zhang, Xiao-Hui,Xu, Yao-Zhong
, p. 887 - 892 (2016/10/24)
Systematic NMR characterization of 4-thio-5-furan-pyrimidine nucleosides or 4-thio-5-thiophene-pyrimidine nucleosides (ribonucleosides and 2′-deoxynucleosides) was performed. All proton and carbon signals of 4-thio-5-thiophene-ribouridine and related analogues were unambiguously assigned. The orientations of the base (4-thiouridine or its deoxy analogue) relative to the ring (furan or thiophene) are explored by a NMR approach and further supported by X-ray crystallographic studies. The procedures presented here would be applicable to other modified nucleosides and nucleotides. Copyright
