4-硫代胸苷 | 7236-57-9

• 物质功能分类: 生物化工 - 核苷类药物 - 核苷中间体
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 4-硫代胸苷
• 英文名称: 4-thiothymidine
• 英文别名: 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-4-sulfanylidenepyrimidin-2-one
• CAS: 7236-57-9
• 化学式: C₁₀H₁₄N₂O₄S
• 分子量: 258.298
• InChiKey: AVKSPBJBGGHUMW-XLPZGREQSA-N

物化性质

• 熔点：
  125-127 °C
• 密度：
  1.52±0.1 g/cm3(Predicted)
• 溶解度：
  水（轻微，超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 储存条件：
  2-8°C，保持干燥环境。

制备方法与用途

硫代胸苷是一种嘌呤核苷类似物，具有广泛的抗肿瘤活性，尤其针对惰性淋巴系统恶性肿瘤。其抗癌机制主要通过抑制DNA合成和诱导细胞凋亡来实现。

反应信息

• 作为反应物：
  描述：

  4-硫代胸苷 在 双氧水 作用下， 以 水 为溶剂， 反应 0.83h， 生成 beta-胸苷
  参考文献：
  名称：

  Potential of 4-thiothymidine as a molecular probe for H2O2 in systems related to PhotoDynamic therapy: A structuristic and mechanistic insight by UV–visible and FTIR-ATR spectroscopies and by ElectroSpray ionization mass spectrometry

  摘要：

  An investigation, based on the synergy between UV-Vis and FTIR-ATR spectroscopies and ElectroSpray Ionization Mass Spectrometry (ESI-MS), on the reactivity of 4-thiothymidine (S-4-TdR) with H2O2 , selected as a Reactive Oxygen Species (ROS) potentially related to Photo Dynamic Therapy (PDT), was performed. The nucleoside main absorption band in the UV-Vis range, centered at 337 nm, was monitored at several reaction times, confirming the S-4-TdR reactivity with a process leading to thymidine (TdR), as the main reaction product, detected through its absorption at 270 nm. Actually, the generation of at least another by-product, absorbing at slightly higher wavelengths compared to S-4-TdR, was inferred from UV-Vis spectra. FTIR-ATR and ESI-MS, MS/MS and MS3 measurements were then performed to unveil the nature of these reaction products, evidencing the presence of a hydroxylated S-4-TdR as important intermediate reaction product. In particular, ESI-MS analyses suggested that the latter was generated as a couple of isomeric compounds, with the OH linked either to the SH group arising from C-4=S tautomerization or to the methyl carbon (C-7) of S-4-TdR. Interestingly, the generation of a covalent dimer of S-4-TdR, characterized by the presence of a disulfide (S-S) bond, was also clearly inferred. The evolution of the cited products with reaction time was also be monitored using ESI-MS, confirming the role of hydroxylated S-4-TdR as an intermediate towards the generation of the ultimate product, TdR. The described processes make S-4-TdR a promising candidate as a molecular probe for the detection of H2O2 in PDT-related systems. (C) 2018 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molliq.2018.05.073
• 作为产物：
  描述：

  beta-胸苷 在 吡啶 、 tetraphosphorus decasulfide 、 氨 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 11.0h， 生成 4-硫代胸苷
  参考文献：
  名称：

  5-取代-4-硫代嘧啶核苷核磁共振谱的系统归属

  摘要：

  使用 NMR 光谱对 5-取代-4-硫代嘧啶核苷（核糖核苷和 2'-脱氧核苷）进行明确表征。5-溴-4-硫尿苷和相关核苷的所有质子和碳信号的分配是通过 COZY 和 HMQC 技术系统地进行并牢固建立的。比较了各种 4-硫代嘧啶核苷的 NMR 数据，并讨论了关键影响因素。这里介绍的方法适用于其他修饰的核苷和核苷酸，以及核碱基。版权所有 © 2013 John Wiley & Sons, Ltd.

  DOI：

  10.1002/mrc.3980

文献信息

• [EN] COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF<br/>[FR] COMPOSÉS COMPRENANT UN LIEUR CLIVABLE ET LEURS UTILISATIONS
  申请人：INTOCELL INC

  公开号：WO2019008441A1

  公开（公告）日：2019-01-10

  Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a SO2 functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.

  提供了一种包括可切割连接物的化合物，其用途，以及用于制备该化合物的中间体化合物，更具体地，本发明的包括可切割连接物的化合物可能包括具有特定功能或活性的活性剂（例如，药物，毒素，配体，用于检测的探针等），能够选择性释放活性剂的SO2官能团，以及通过外部刺激触发化学反应，物理化学反应和/或生物反应的官能团，并且还可以包括具有与所需靶受体结合特异性的配体（例如，寡肽，多肽，抗体等）。
• NMR and UV Studies of 4-Thio-2′-deoxyuridine and Its Derivatives
  作者：Xiaohui Zhang、Yao-Zhong Xu

  DOI：10.3390/molecules16075655

  日期：——

  5-Substituted-4-thio-2'-deoxyuridine nucleosides have been chemically synthesized and studied by NMR and UV spectroscopy. The results have been analyzed and discussed in connection with the previous data. The imino proton signal and the carbon signal of the thiocarbonyl group in the 5-substituted-4-thio-2'-deoxyuridines were found to be at much lower field, offering a potential for monitoring these

  5-Substituted-4-thio-2'-deoxyuridine nucleosides 已被化学合成并通过 NMR 和 UV 光谱进行了研究。已经结合先前的数据对结果进行了分析和讨论。发现 5-取代-4-硫代-2'-脱氧尿苷中的亚氨基质子信号和硫代羰基的碳信号处于低得多的场中，为在 DNA 水平上监测这些修饰碱基提供了潜力。所有 4-硫代核苷在 340 nm 附近都有很强的吸收，因此可用作潜在的 UVA 诱导的抗癌剂。
• Antiviral Activity of Various 1-(2′-Deoxy-β-<scp>d</scp>-lyxofuranosyl), 1-(2′-Fluoro-β-<scp>d</scp>-xylofuranosyl), 1-(3′-Fluoro-β-<scp>d</scp>-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
  作者：Naveen C. Srivastav、Neeraj Shakya、Michelle Mak、Babita Agrawal、D. Lorne Tyrrell、Rakesh Kumar

  DOI：10.1021/jm100803c

  日期：2010.10.14

  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′-d

  尽管存在成功的疫苗和抗病毒疗法，但乙型肝炎病毒（HBV）的感染仍然是急性和慢性肝病以及高死亡率的全球主要原因。我们合成并评估了几种lyxofuranosyl，2'-fluorooxylofuranosyl，3'-fluoroarabinofuranosyl和2'-fluoro-2'，3'-didehydro-2'，3'-dideoxyribose嘧啶核苷类似物对乙型肝炎病毒的抗病毒活性。在所检查的化合物中，1-（2-脱氧-β - d-呋喃呋喃糖基）胸腺嘧啶（23），1-（2-脱氧-β - d-呋喃呋喃糖基）-5-三氟甲基尿嘧啶（25），1-（2-脱氧-2-氟-β - d-木呋喃糖基）尿嘧啶（38），1-（2-脱氧-2-氟-β- d-二呋喃呋喃糖基）胸腺嘧啶（39），2'，3'-二脱氧-2'，3'-二脱氢-2'-氟胸苷（48）和2'，3'-二脱氧-2'，3'-二脱氢-2在原代鸭肝细胞中发现'
• Progress toward an amplifiable metabolic label for DNA: conversion of 4-thiothymidine (4sT) to 5-methyl-2′-deoxycytidine and synthesis of a 4sT phosphorodiamidate prodrug
  作者：Adam K. Hedger、Marlies E. Oomen、Victor Liu、Michael P. Moazami、Nicholas Rhind、Job Dekker、Jonathan K. Watts

  DOI：10.1139/cjc-2017-0732

  日期：2018.7

  selected 4-thiothymidine (4sT) as a candidate metabolic label: 4sT is readily taken up by a large number of polymerases in vitro, and we present a method that allows 4sT to be converted into 5-methyl-2′-deoxycytidine (5mC) after incorporation into DNA. Encouraged by these results, we treated cells with 4sT nucleoside; however, we found that 4sT is not incorporated into DNA in bacterial, yeast, or mammalian

  以产生从一个核碱基到另一个核碱基的潜在变化的方式代谢标记 DNA 的能力将产生可以通过 PCR 放大的信号——这反过来又将允许使用高通量测序研究新合成的 DNA。为了起到可放大的代谢标记的作用，核苷酸类似物需要被细胞吸收并整合到细胞 DNA 中；DNA 纯化后，可以将其转化为具有不同碱基配对模式的不同核碱基。我们选择 4-硫胸苷 (4sT) 作为候选代谢标记：4sT 在体外很容易被大量聚合酶吸收，我们提出了一种方法，可以将 4sT 转化为 5-甲基-2'-脱氧胞苷 (5mC ) 掺入 DNA 后。受这些结果的鼓舞，我们用 4sT 核苷处理细胞；然而，我们发现在我们测试的条件下，4sT 并没有以有用的水平掺入细菌、酵母或哺乳动物细胞的 DNA 中。4sTMP 的磷酰二胺前药是...
• LABELING METHOD FOR NUCLEIC ACID
  申请人：Kyushu University, National University Corporation

  公开号：US20200308635A1

  公开（公告）日：2020-10-01

  Provided is a labeling method for nucleic acid including a reaction step for hybridizing a nucleic acid probe that has a nucleotide sequence complementary to that of a nucleic acid to be labeled and contains a reactive nucleobase derivative incorporated at a position complementary to that of a target nucleobase as a target of labeling in the nucleic acid to be labeled, to the nucleic acid to be labeled; a transferring step for transferring a transfer group contained in the reactive nucleobase derivative to the nucleotide residue containing the target nucleobase in the nucleic acid to be labeled; and a labeling step for labeling the transfer group transferred to the nucleotide residue with a radioactive material.

  提供了一种核酸标记方法，包括以下步骤：反应步骤，用于杂交含有与待标记核酸互补的核苷酸序列，并在与目标核苷酸互补的位置上含有反应性核碱基衍生物的核酸探针，以将其标记到待标记的核酸上；转移步骤，用于将反应性核碱基衍生物中包含的转移基团转移至待标记的核酸中含有目标核碱基的核苷酸残基上；以及标记步骤，用于将转移至核苷酸残基上的转移基团与放射性物质标记。