2’-O-甲基5-碘代尿苷 | 34218-84-3

• 物质功能分类: 有机原料
• 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: 2’-O-甲基5-碘代尿苷
• 中文别名: 2'-甲氧基-5-碘-尿苷；5-碘-2-o-甲基-尿苷
• 英文名称: 1-((2R,3R,4R,5R)-4-hydroxy-5-(hydroxymethyl)-3-methoxy-tetrahydrofuran-2-yl)-5-iodopyrimidine-2,4(1H,3H)-dione
• 英文别名: 1-((2R,3R,4R,5R)-4-hydroxy-5-(hydroxymethyl)-3-methoxytetrahydrofuran-2-yl)-5-iodopyrimidine-2,4(1H,3H)-dione；2′-O-methyl-5-iodouridine；5-iodo-2’-O-methyluridine；5-Iodo-2'-O-methyluridin；5-Iodo-2'-O-methyluridine；1-[(2R,3R,4R,5R)-4-hydroxy-5-(hydroxymethyl)-3-methoxyoxolan-2-yl]-5-iodopyrimidine-2,4-dione
• CAS: 34218-84-3
• 化学式: C₁₀H₁₃IN₂O₆
• 分子量: 384.128
• InChiKey: PLVDDNNLEWFJNQ-JXOAFFINSA-N

物化性质

• 密度：
  2.04±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P210,P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P332+P313,P337+P313,P362,P370+P378,P403+P233,P403+P235,P405,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2’-O-甲基5-碘代尿苷 在 吡啶 、 4-二甲氨基吡啶 、 copper(l) iodide 、 四(三苯基膦)钯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 66.0h， 生成 5-(octa-1,7-diynyl)-5’-O-(4,4’-dimethoxytrityl)-2’-O-methyluridine
  参考文献：
  名称：

  Efficient Tandem Copper‐Catalyzed Click Synthesis of Multisugar‐Modified Oligonucleotides

  摘要：

  Nucleic acids in the form of siRNA, antisense oligonucleotides or mRNA are currently explored as new promising modalities in the pharmaceutical industry. Particularly, the success of mRNA‐vaccines against SARS‐CoV‐2, along with the successful development of the first sugar‐modified siRNA therapeutics has inspired the field. The development of nucleic acid therapeutics requires efficient chemistry to link oligonucleotides to chemical structures that can improve stability, boost cellular uptake, or enable specific targeting. For the siRNA therapeutics currently in use, modification of the 3′‐end of the oligonucleotides with triple‐N‐acetylgalactosamine (GalNAc)3 was shown to be of significance. This modification is currently achieved through cumbersome multistep synthesis and subsequent loading onto the solid support material. Herein, we report the development of a bifunctional click‐reactive linker that allows the modification of oligonucleotides in a tandem click reaction with multiple sugars, regardless of the position within the oligonucleotide, with remarkable efficiency and in a one‐pot reaction.

  DOI：

  10.1002/anie.202405161
• 作为产物：
  描述：

  2'-甲氧基尿苷 在 ammonium cerium (IV) nitrate 、 碘 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以86%的产率得到2’-O-甲基5-碘代尿苷
  参考文献：
  名称：

  半刚性的异吲哚啉衍生的一氧化氮自旋标记，用于RNA †

  摘要：

  合成了新的异吲哚啉衍生的苯并咪唑一氧化氮自旋标记Im Um，并将其掺入RNA寡核糖核苷酸中。Im Um是RNA构象明确的自旋标记的第一个例子，其中的氮氧化物N–O键与用于将基于刚性二氢吲哚啉的自旋标记附着于尿苷碱基的单键位于同一轴上。这导致该单键旋转时氮氧化物的位移最小，这对于用于距离测量的标签是有用的属性。含Im Um的RNA双链体的连续波（CW）EPR测量表示围绕该单键的旋转受限，可能是由于苯并咪唑N–H和尿嘧啶O4之间存在分子内氢键。两种RNA双链体中两个自旋标记之间的方向选择脉冲电子-电子双共振（PELDOR，也称为双电子-电子共振或DEER）距离测量在一种情况下显示出强烈的方向依赖性，进一步证实了自旋运动受限制RNA双链体中的标记。

  DOI：

  10.1039/c7ob02870a

文献信息

• [EN] S-ANTIGEN TRANSPORT INHIBITING OLIGONUCLEOTIDE POLYMERS AND METHODS<br/>[FR] POLYMÈRES OLIGONUCLÉOTIDIQUES INHIBANT LE TRANSPORT DE L'ANTIGÈNE S ET MÉTHODES
  申请人：ALIGOS THERAPEUTICS INC

  公开号：WO2021119325A1

  公开（公告）日：2021-06-17

  Various embodiments provide STOPS™ polymers that are S-antigen transport inhibiting oligonucleotide polymers, processes for making them and methods of using them to treat diseases and conditions. In some embodiments the STOPS™ modified oligonucleotides include an at least partially phosphorothioated sequence of alternating A and C units having modifications as described herein. The sequence independent antiviral activity against hepatitis B of embodiments of STOPS™ modified oligonucleotides, as determined by HBsAg Secretion Assay, is an EC50 that is less than 100 nM.

  各种实施方式提供了STOPS™聚合物，这些聚合物是S-抗原转运抑制寡核苷酸聚合物，提供了制备它们的方法以及使用它们治疗疾病和症状的方法。在某些实施方式中，STOPS™修饰的寡核苷酸包括至少部分磷硫酸酯化的交替A和C单元序列，具有如本文所述的修饰。通过HBsAg分泌测定确定的STOPS™修饰的寡核苷酸对乙型肝炎的序列无关抗病毒活性，其EC50小于100 nM。
• [EN] IDOXURIDINE AND ITS ANALOGS AS NEUROPROTECTANS FOR THE TREATMENT OF PARKINSONISM<br/>[FR] IDOXURIDINE ET SES ANALOGUES UTILISÉS COMME NEUROPROTECTEURS POUR LE TRAITEMENT DU PARKINSONISME
  申请人：SVENNINGSSON PER

  公开号：WO2018143893A1

  公开（公告）日：2018-08-09

  The invention relates to compounds that are useful in the treatment of parkinsonism, such as parkinsonism in connection with Parkinson's disease (PD); dementia with Lewy bodies (DLB); multiple system atrophy (MSA); corticobasal degeneration (CBD); or progressive supranuclear palsy (PSP). The said compounds include in particular idoxuridineand analogs thereofas well as their metabolic precursors, such as ropidoxuridine.The invention further relates to method for identifying compounds useful for the treatment of parkinsonism, said methods comprising detecting the capability of compound to increase the amount of GPR37 in cell membranes.The invention further relates to methods for the chemical synthesis of ropidoxuridine.

  本发明涉及一种在帕金森病（PD）相关的帕金森综合征，如帕金森病（PD）；具有Lewy小体的痴呆（DLB）；多系统萎缩（MSA）；皮质基底节变性（CBD）；或进行性核上性麻痹（PSP）等治疗中有用的化合物。所述化合物包括特别是碘沙宝嘌呤及其类似物以及它们的代谢前体，如罗匹沙宝嘌呤。本发明还涉及一种用于鉴定治疗帕金森综合征的有用化合物的方法，该方法包括检测化合物增加细胞膜中GPR37数量的能力。本发明还涉及罗匹沙宝嘌呤的化学合成方法。
• Towards Improved Oligonucleotide Therapeutics Through Faster Target Binding Kinetics
  作者：Mirjam Menzi、Bettina Wild、Ugo Pradère、Anna L. Malinowska、Andreas Brunschweiger、Helen L. Lightfoot、Jonathan Hall

  DOI：10.1002/chem.201701670

  日期：2017.10.12

  Nature-inspired modification of RNA for faster hybridization: The conjugation of spermine groups using a triazole linker to 2′-O-methyloligoribonucleo tides leads to accelerated binding to complementary RNAs. The conjugated fragments in the major groove mimic the actions of natural polyamines with cellular RNAs and greatly increase hybridization affinities.

  大自然启发的RNA修饰，可实现更快的杂交：使用三唑接头将精胺基团与2'- O-甲基寡核糖核苷酸核苷酸结合，可加速与互补RNA的结合。主沟中的缀合片段模仿天然多胺与细胞RNA的作用，并大大提高了杂交亲和力。
• EXTRAHEPATIC DELIVERY
  申请人：ALNYLAM PHARMACEUTICALS, INC.

  公开号：US20220125823A1

  公开（公告）日：2022-04-28

  The invention relates to a method of gene silencing, comprising administering to a cell or a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs at one or more internal positions on at least one strand, optionally via a linker or carrier.

  本发明涉及一种基因沉默方法，包括向细胞或需要治疗的受体中给予脂溶性基团偶联的双链iRNA，在至少一条链的一个或多个内部位置上给予治疗有效量，可选地通过连接剂或载体给予。
• DELIVERY OF OLIGONUCLEOTIDES TO THE STRIATUM
  申请人：ALNYLAM PHARMACEUTICALS, INC.

  公开号：US20220307024A1

  公开（公告）日：2022-09-29

  One aspect of the present invention relates to a double stranded iRNA agent comprising an antisense strand which is complementary to a target gene; a sense strand which is complementary to said antisense strand; and one or more lipophilic moieties conjugated to one or more internal positions on at least one strand, optionally via a linker or carrier, which provides for targeting to, and uptake by, tissues and cells of the CNS, and in particular the striatum. Another aspect of the invention relates to a method of gene silencing in tissues and cells of the CNS, and in particular the striatum, that includes administering to a tissue/cell or a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs.

  本发明的一个方面涉及双链iRNA剂，包括一个与目标基因互补的反义链;一个与该反义链互补的正义链;以及一个或多个脂溶性基团，通过连接物或载体与至少一条链上的一个或多个内部位置结合，从而实现对中枢神经系统组织和细胞，特别是纹状体的靶向和摄取。本发明的另一个方面涉及一种在中枢神经系统组织和细胞，特别是纹状体中基因沉默的方法，包括向需要治疗的组织/细胞或受试者中注射足够疗效量的脂溶性基团结合的双链iRNA。