55003-25-3Relevant academic research and scientific papers
Generation of thiyl radicals by the photolysis of 5-iodo-4-thiouridine
Wenska, Grazyna,Taras-Goslinska, Katarzyna,Skalski, Bohdan,Hug, Gordon L.,Carmichael, Ian,Marciniak, Bronislaw
, p. 982 - 988 (2005)
(Chemical Equation Presented) The photochemistry of 2′,3′, 5′-tri-O-acetyl-5-iodo-4-thiouridine (3) in deoxygenated 1:1 CH 3CN-H2O pH 5.8 (phosphate buffer) solution has been studied by means of steady-state and nanosecond laser flash photolysis methods. Under steady-state irradiation (λ ≥ 334 nm), the stable photoproducts were iodide ion, 2′,3′,5′-tri-O-acetyl-4-thiouridine (4), and two disulfides. The disulfides were the symmetrical bis-(2′,3′, 5′-tri-O-acetyl-5-iodo-4-thiouridine) (5) and unsymmetrical 6, which contains both 4-thiouridine and 5-iodo-4-thiouridine residues. The formation of the dehalogenated photoproduct suggests that C(S)-I bond cleavage is a primary photochemical step. Attempts to scavenge the resulting C(5)-centered radical by suitable addends, bis-(N-α-acetyl)cystine-bis-N-ethylamide or benzene, were unsuccessful. Analysis of the photoproducts formed under these conditions showed that the S-atom is the reactive center. The photoproduct 4, obtained by irradiation of 3 in CD3-CN-H2O, followed by reversed-phase HPLC isolation using nonlabeled eluents, did not contain deuterium. An analogous experiment performed in CH3CN-D2O gave deuterated product 4-d with 88% of the deuterium incorporated at C(5). Transient absorption observed upon laser excitation (λ = 308 nm) of 3 was assigned to the 4-uridinylthiyl radical on the basis of the similarity of this spectrum with that obtained upon laser photolysis of the disulfide: bis-(2′, 3′,5′-tri-O-acetyl-4-thiouridine) 14. On the basis of the results of steady-state and laser photolysis studies, a mechanism of the photochemical reaction of 3 is proposed. The key mechanistic step is a transformation of the C(5)-centered radical formed initially by C(5)-I bond cleavage into a long-lived S-centered radical via a 1,3-hydrogen shift. Theoretical calculations confirmed that the long-lived S-centered radical is the most stable radical derived from the 4-thiouracil residue.
Anti-hepatitis B virus compound as well as preparation method and application thereof
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Paragraph 0029-0032, (2021/06/22)
The invention provides an anti-hepatitis B virus compound and a preparation method and application thereof, the compound is 4-thiouridine isobutyrate, the molecular formula is C13H18N2O6S, and the structural formula is shown in the specification. The compound provided by the invention can effectively inhibit the activity of hepatitis B virus, can be used as a substitute drug for lamivudine and telbivudine, solves the problem of drug resistance of lamivudine and the like in the aspect of resisting hepatitis B virus, is high in drug effect, low in toxicity and low in price, and provides a direction for development of drugs for treating hepatitis B. In addition, the invention discloses a preparation method of the compound 4-thiouridine isobutyrate, and the preparation method is mild in condition, easy to synthesize and suitable for industrial production.
Systematic assignment of NMR spectra of 5-substituted-4-thiopyrimidine nucleosides
Zhang, Xiaohui,Wang, Jian,Xu, Yao-Zhong
, p. 523 - 529 (2013/09/02)
Unambiguous characterization of 5-substituted-4-thiopyrimidine nucleosides (ribonucleosides and 2'-deoxynucleosides) was performed using NMR spectroscopy. Assignments of all proton and carbon signals of 5-bromo-4-thiouridine and related nucleosides were systematically carried out and firmly established by COSY and HMQC techniques. The NMR data of various 4-thiopyrimidine nucleosides are compared, and the key contributing factors discussed. The approach presented here is applicable to other modified nucleosides and nucleotides, as well as nucleobases. Copyright
Structural modifications of UMP, UDP, and UTP leading to subtype-selective agonists for P2Y2, P2Y4, and P2Y6 receptors
El-Tayeb, Ali,Qi, Aidong,Nicholas, Robert A.,Müller, Christa E.
supporting information; experimental part, p. 2878 - 2890 (2011/06/24)
A large series of derivatives and analogues of the uracil nucleotides UMP, UDP, and UTP with modifications in various positions of the uracil moiety and/or the phosphate groups were synthesized and evaluated at human P2Y2, P2Y4, and P2Y6 receptors. 2-(Ar)alkylthio substitution of UMP and UDP was best tolerated by the P2Y2 receptor. 2-Phenethylthio-UMP (13e) showed an EC50 value of 1.3 μM at P2Y2 and >70-fold selectivity versus P2Y4 and P2Y 6 receptors. Substitution of the 2-keto group in UMP by NH (13g, iso-CMP) resulted in the first potent and selective P2Y4 agonist (EC50 4.98 μM, >20-fold selective vs P2Y2 and P2Y6). In contrast, replacement of the 2-keto function in UDP by NH yielded a potent P2Y2 agonist (12g, iso-CDP, EC50 = 0.604 μM, >100-fold selective). In an attempt to obtain metabolically stable UTP analogues, β,γ-dichloro- and β,γ-difluoro-methylene-UTP derivatives were synthesized. The triphosphate modifications were much better tolerated by P2Y2, and in some cases also by P2Y6, than by P2Y4 receptors. 4-Thio-β,γ-difluoromethylene-UTP (14g) was a potent P2Y2 agonist with an EC50 value of 0.134 μM and >50-fold selectivity. N3-Phenacyl-β,γ-dichloromethylene- UTP (14b) proved to be a potent P2Y6 receptor agonist (EC 50 0.142 μM) with high selectivity versus P2Y4 (50-fold) and moderate selectivity versus P2Y2 receptors (6-fold).
Thionation using fluorous Lawesson's reagent
Kaleta, Zoltan,Makowski, Brian T.,Soos, Tibor,Dembinski, Roman
, p. 1625 - 1628 (2007/10/03)
Thionation of amides, 1,4-diketones, N-(2-oxoalkyl)amides, N,N-acylhydrazines, and acyl-protected uridines with the use of a fluorous analogue of the Lawesson's reagent leads to thioamides, thiophenes, 1,3-thiazoles, 1,3,4-thiadiazoles, and acyl-protected 4-thiouridines. The isolation of the final products in high yields is achieved in most cases by a simple filtration (fluorous solid-phase extraction).
Synthesis of oligoribonucleotides containing 4-thiouridine using the convertible nucleoside approach and the 1-(2-fluorophenyl)-4-methoxypiperidin-4- yl group
Avino, Anna,Garcia, Ramon Gueimil,Eritja, Ramon
, p. 1767 - 1777 (2007/10/03)
Oligoribonucleotides containing 4-thiouridine were prepared using the Fpmp group for protection of the 2′-OH. Two uridine derivatives with the 1,2,4-triazolyl and the 2-nitrophenyl groups at position 4 were used to obtain 4-thiouridine by postsynthetic su
4-Substituted uridine 5′-triphosphates as agonists of the P2y2 purinergic receptor
Shaver, Sammy R.,Pendergast, William,Siddiqi, Suhaib M.,Yerxa, Benjamin R.,Croom, Dallas K.,Dougherty, Robert W.,James, Michael K.,Neil Jones,Rideout, Janet L.
, p. 1099 - 1102 (2007/10/03)
Undine 5′-O-triphosphate (UTP) is a potent agonist of the purinergic receptor designated P2Y2. UTP is rapidly metabolized in human tissue. To find a compound with similar activity that may be more slowly metabolized, a series of 4-substituted uridine 5′-triphosphates were prepared and evaluated in a P2Y2 receptor second messenger assay. Copyright
Chemical Conversion of Uridine into 4-Thiouridine via the 4-(1,2,4-Triazol-1-yl)pyrimidin-2(1H)-one Intermediate
Sung, Wing L.
, p. 522 - 523 (2007/10/02)
In an aqueous solution of sodium hydrosulphide at room temperature, 4-(1,2,4-triazol-1-yl)-1-(2',3',5'-tri-O-acetyl-β-D-ribofuranosyl)pyrimidin-2(1H)-one, prepared from uridine, is converted into the 4-thiopyrimidin-2(1H)-one derivative which can be deacetylated to yield 4-thiouridine.
