1-(2'-deoxy-5'-O-4,4'-dimethoxytrityl-β-D-threo-pentofuranosyl)-thymine

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 1-(2'-deoxy-5'-O-4,4'-dimethoxytrityl-β-D-threo-pentofuranosyl)-thymine
• 英文别名: 1-((2R,4R,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-hydroxytetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)- dione；1-((2R,4R,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-hydroxy-tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione；1-[(2R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• 化学式: C₃₁H₃₂N₂O₇
• 分子量: 544.604
• InChiKey: UBTJZUKVKGZHAD-JCYYIGJDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(2'-deoxy-5'-O-4,4'-dimethoxytrityl-β-D-threo-pentofuranosyl)-thymine 在 吡啶 、 盐酸 、 二乙胺基三氟化硫 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 0.17h， 生成 3’-脱氧-3-氟胸苷
  参考文献：
  名称：

  Radiolabeled Cyclosaligenyl Monophosphates of 5-Iodo-2′-deoxyuridine, 5-Iodo-3′-fluoro-2′,3′-dideoxyuridine, and 3′-Fluorothymidine for Molecular Radiotherapy of Cancer: Synthesis and Biological Evaluation

  摘要：

  Targeted molecular radiotherapy opens unprecedented opportunities to eradicate cancer cells with minimal irradiation of normal tissues. Described in this study are radioactive cyclosaligenyl monophosphates designed to deliver lethal doses of radiation to cancer cells. These compounds can be radiolabeled with SPECT- and PET-compatible radionuclides as well as radionuclides suitable for Auger electron therapies. This characteristic provides an avenue for the personalized and comprehensive treatment strategy that comprises diagnostic imaging to identify sites of disease, followed by the targeted molecular radiotherapy based on the imaging results. The developed radiosynthetic methods produce no-carrier-added products with high radiochemical yield and purity. The interaction of these compounds with their target, butyrylcholinesterase, depends on the stereochemistry around the P atom. 1050 values are in the nanomolar range. In vitro studies indicate that radiation doses delivered to the cell nucleus are sufficient to kill cells of several difficult to treat malignancies including glioblastoma and ovarian and colorectal cancers.

  DOI：

  10.1021/jm201482p
• 作为产物：
  描述：

  保护胸苷 在 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 1-(2'-deoxy-5'-O-4,4'-dimethoxytrityl-β-D-threo-pentofuranosyl)-thymine
  参考文献：
  名称：

  探讨修饰核苷与 DNA 核酸酶 SNM1A 的结合要求

  摘要：

  SNM1A 是一种涉及 DNA 链间交联修复的核酸酶，因此，它的抑制作用对于克服对化学治疗性交联剂的抗性很重要。然而，SNM1A活性位点中金属离子的数量和身份仍未得到证实，迄今为止报道的抑制剂数量有限。在此，我们报告了基于丙二酸的修饰核苷家族的合成和评估，以研究金属结合基团在核苷衍生的 SNM1A 抑制剂中的最佳定位。这些化合物包括酯、羧酸酯和异羟肟酸丙二酸酯衍生物，它们安装在胸苷的 5'-位或 3'-位或作为两个核苷之间的连接。作为重组 SNM1A 抑制剂的评估表明，所测试的 12 种化合物中有 9 种在 1 mM 浓度下具有抑制作用。最有效的化合物在 5'-位含有异羟肟酸丙二酸酯基团。总体而言，我们的研究促进了对 SNM1A 核苷衍生抑制剂要求的理解，并表明在金属螯合剂（如异羟肟酸丙二酸酯）附近含有带负电荷基团的基团是抑制剂设计中很有前景的结构。

  DOI：

  10.3390/molecules26020320

文献信息

• Selective Cleavage of O-(Dimethoxytrityl) Protecting Group with Sodium Periodate
  作者：Dominik Rejman、Šárka Králíková、Zdeněk Točík、Radek Liboska、Ivan Rosenberg

  DOI：10.1135/cccc20020502

  日期：——

  Sodium periodate in aqueous organic solvents selectively removes, under mild reaction conditions, the O-(dimethoxytrityl) protecting group. Selectivity of the cleavage was studied using the nucleoside derivatives protected by various types of groups commonly used in nucleoside and nucleotide chemistry.

  在水有机溶剂中，过碘酸钠在温和的反应条件下选择性地去除了O-(二甲氧基三苯甲基)保护基团。利用核苷衍生物进行了裂解的选择性研究，这些核苷衍生物受到核苷和核苷酸化学中常用的各种基团的保护。
• Synthesis and evaluation of 3′-[¹⁸F]fluorothymidine-5′-squaryl as a bioisostere of 3′-[¹⁸F]fluorothymidine-5′-monophosphate
  作者：D. Brickute、A. Beckley、L. Allott、M. Braga、C. Barnes、K. J. Thorley、E. O. Aboagye

  DOI：10.1039/d1ra00205h

  日期：——

  greater cell permeability. It has been used in the synthesis of several therapeutic drug molecules including nucleoside and nucleotide analogues but is yet to be evaluated in the context of positron emission tomography (PET) imaging. We have designed, synthesised and evaluated 3'-[18F]fluorothymidine-5'-squaryl ([18F]SqFLT) as a bioisostere to 3'-[18F]fluorothymidine-5'-monophosphate ([18F]FLTMP) for

  方芳基部分已成为一种重要的磷酸盐生物等排体，据报道具有更大的细胞渗透性。它已用于合成多种治疗药物分子，包括核苷和核苷酸类似物，但尚未在正电子发射断层扫描 (PET) 成像的背景下进行评估。我们设计、合成并评估了 3'-[18F]氟胸苷-5'-方酸 ([18F]SqFLT) 作为 3'-[18F]氟胸苷-5'-单磷酸 ([18F]FLTMP) 的生物等排体，用于胸苷酸成像激酶 (TMPK) 活性。总放射化学收率（RCY）为 6.7 ± 2.5%，放射化学纯度（RCP）>90%。体外生物学评估显示示踪剂摄取量较低（<0.3% ID mg-1），但野生型 HCT116 和 CRISPR/Cas9 生成的 TMPK 敲低 HCT116shTMPK- 之间存在显着差异。 HCT116 和 HCT116shTMPK 异种移植小鼠模型中的 [18F]SqFLT 评估显示肿瘤摄取具有统计学显着差异，但缺乏
• [EN] MODIFIED OLIGOMERIC COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS OLIGOMÈRES MODIFIÉS ET LEURS UTILISATIONS
  申请人：IONIS PHARMACEUTICALS INC

  公开号：WO2021030763A1

  公开（公告）日：2021-02-18

  The present disclosure provides oligomeric compounds comprising a modified oligonucleotide having at least one stereo-non-standard nucleoside. An oligomeric compound comprising a modified oligonucleotide consisting of 12-30 linked nucleosides, wherein at least one nucleoside of the modified oligonucleotide is a stereo-non-standard nucleoside; and wherein the oligomeric compound is selected from among an RNAi compound, a modified CRISPR compound, and an artificial mRNA compound.

  本公开提供了包含至少一种立体非标准核苷酸的修饰寡核苷酸的寡聚化合物。包括由12-30个连接的核苷酸组成的修饰寡核苷酸的寡聚化合物，其中修饰寡核苷酸的至少一个核苷酸是立体非标准核苷酸；且所述寡聚化合物选自RNAi化合物、修饰CRISPR化合物和人工mRNA化合物。
• Nucleosidyl‐<i>O</i>‐Methylphosphonates: A Pool of Monomers for Modified Oligonucleotides
  作者：Dominik Rejman、Milena Masojídková、Ivan Rosenberg

  DOI：10.1081/ncn-200033912

  日期：2004.1.1

  2′‐deoxyribonucleosides, 1‐(2‐deoxy‐β‐D‐threo‐pentofuranosyl)thymine, 5′‐O‐ and 2′‐O‐phosphonomethyl derivatives of 1‐(3‐deoxy‐β‐D‐erythro‐pentofuranosyl)thymine, and 1‐(3‐deoxy‐β‐D‐threo‐pentofuranosyl)thymine has been synthesized as a pool of monomers for the synthesis of modified oligonucleotides. The phosphonate moiety was protected with 4‐methoxy‐1‐oxido‐2‐pyridylmethyl ester group, serving also as an intramolecular

  四种天然 2'-脱氧核糖核苷、1-（2-脱氧-β-D-苏式-戊呋喃糖基）胸腺嘧啶、5'-O- 和 2' 的一组独特的 5'-O- 和 3'-O-膦酰基甲基衍生物1-(3-脱氧-β-D-赤型-戊呋喃糖基)胸腺嘧啶和1-(3-脱氧-β-D-苏式-戊呋喃糖基)胸腺嘧啶的-O-膦酰基甲基衍生物已被合成为单体库修饰寡核苷酸的合成。膦酸酯部分用 4-甲氧基-1-氧化-2-吡啶基甲酯基团保护，在偶联步骤中也作为分子内催化剂。
• Radiologic Agents for Monitoring Alzheimer's Disease Progression and Evaluating a Response to Therapy and Processes for the Preparation of Such Agents
  申请人：Kortylewicz Zbigniew P.

  公开号：US20090117041A1

  公开（公告）日：2009-05-07

  Disclosed are certain cycloSalingenyl pyrimidine nucleoside monophosphates comprising positron emitters or gamma-emitting radiohalides, uses thereof for monitoring Alzheimer's disease progression and evaluating response to therapy and process for their preparation.

  本文披露了包含正电子发射体或伽马辐射放射性卤化物的某些环丝氨基嘧啶核苷酸单磷酸盐，其用于监测阿尔茨海默病的进展并评估对治疗的反应，以及它们的制备过程。