6-甲基尿苷 | 16710-13-7

• 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: 6-甲基尿苷
• 英文名称: 6-methyluridine
• 英文别名: 1β-D-ribofuranosyl-6-methyluracil；N¹-6-methyluridine；6-methyl uridine；6-methyl-uridine；m⁶U；6-Methyl-uridin；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-methylpyrimidine-2,4-dione
• CAS: 16710-13-7
• 化学式: C₁₀H₁₄N₂O₆
• 分子量: 258.231
• InChiKey: SGKGZYGMLGVQHP-ZOQUXTDFSA-N

物化性质

• 密度：
  1.576±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  18
• 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：
  119
• 氢给体数：
  4
• 氢受体数：
  6

制备方法与用途

6-甲基尿苷是一种尿苷类似物，而尿苷本身具备潜在的抗癫痫效果。通过研究类似物，可以探索其抗惊厥和抗焦虑活性，并为进一步开发新型抗高血压药物提供参考。

反应信息

• 作为反应物：
  描述：

  6-甲基尿苷 在 Escherichia coli uridine phosphorylase 、 磷酸肌酸 作用下， 以 aq. phosphate buffer 为溶剂， 生成 6-甲基尿嘧啶
  参考文献：
  名称：

  大肠杆菌尿苷磷酸化酶的底物特异性。尿苷磷酸分解中底物的高syn构象的进一步证据

  摘要：

  摘要已经测试了二十五个尿苷类似物，并就其与大肠杆菌尿苷磷酸化酶的结合能力与尿苷进行了比较。确定了在糖部分的2'-，3'-和5'-位以及杂环碱基的2-，4-，5-和6-位上修饰的尿苷衍生物的磷酸分解反应的动力学常数。2'-或5'-羟基的不存在对于成功的结合和磷酸分解不是至关重要的。另一方面，2'-和5'-羟基均不存在导致底物与酶结合的丧失。当不存在3'-羟基时，观察到相同的效果，从而强调了该基团的关键作用。我们的数据阐明了大肠杆菌尿苷磷酸化酶和大肠杆菌对核糖和2'-脱氧核糖核苷的识别机制。大肠杆菌胸苷磷酸化酶。在本研究中获得的动力学结果与可用的X射线结构进行比较，并对酶-底物复合物中的氢键进行分析，结果表明尿苷在尿苷磷酸化酶的活性位点采用了不同寻常的高Syn构象。

  DOI：

  10.1080/15257770.2016.1223306
• 作为产物：
  描述：

  6-甲基尿嘧啶 在 甲醇 、 N,O-双三甲硅基乙酰胺 、 氨 作用下， 以 乙腈 为溶剂， 反应 11.33h， 生成 6-甲基尿苷
  参考文献：
  名称：

  NMR-based conformational analysis of 2′,6-disubstituted uridines and antiviral evaluation of new phosphoramidate prodrugs

  摘要：

  Six novel phosphoramidate prodrugs of uridine analogues, with structural modifications introduced at the 6- and 2',6-positions, have been prepared and evaluated for selective antiviral activity against hepatitis C virus, as well as other positive-stranded RNA viruses. An analysis of the conformational properties of the parent nucleosides was carried out using two-dimensional NMR spectroscopy based experiments, highlighting a 3'-endo (North) sugar puckering preference and syn orientation. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.003

文献信息

• IONIZABLE CATIONIC LIPID FOR RNA DELIVERY
  申请人：Arcturus Therapeutics, Inc.

  公开号：US20180169268A1

  公开（公告）日：2018-06-21

  What is described is a compound of formula I consisting of a compound in which R 1 is a branched chain alkyl consisting of 10 to 31 carbons; R 2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons; L 1 and L 2 are the same or different, each a linear alkylene of 1 to 20 carbons or a linear alkenylene of 2 to 20 carbons; X 1 is S or O; R 3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R 4 and R 5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.

  描述的是一种化合物，其化学式为I，包括以下成分： R1为由10至31个碳组成的支链烷基化合物； R2为由2至20个碳组成的直链烷基、烯基或炔基； L1和L2相同或不同，每个为由1至20个碳组成的直链烷基或由2至20个碳组成的直链烯基； X1为S或O； R3为由1至6个碳组成的直链或支链烷基； R4和R5相同或不同，每个为氢或由1至6个碳组成的直链或支链烷基；或其药用可接受盐。
• DUPLEX OLIGONUCLEOTIDE COMPLEXES AND METHODS FOR GENE SILENCING BY RNA INTERFERENCE
  申请人：Yamada Christina

  公开号：US20080085869A1

  公开（公告）日：2008-04-10

  Provided herein are duplex oligonucleotide complexes which can be administered to a cell, tissue or organism to silence a target gene without the aid of a transfection reagent(s). The duplex oligonucleotide complexes of the disclosure include a conjugate moiety that facilitates delivery to a cell, tissue or organism.

  本文提供了一种双链寡核苷酸复合物，可以被输送到细胞、组织或生物体中，以沉默目标基因，而无需转染试剂的帮助。本公开的双链寡核苷酸复合物包括一个共轭基团，有助于将其输送到细胞、组织或生物体中。
• Novel compositions for the delivery of negatively charged molecules
  申请人：Ribozyme Pharmaceuticals, Inc.

  公开号：US20030073640A1

  公开（公告）日：2003-04-17

  This invention features permeability enhancer molecules, and methods, to increase membrane permeability of various molecules, such as nucleic acids, polynucleotides, oligonucleotides, enzymatic nucleic acid molecules, antisense nucleic acid molecules, 2-5A antisense chimeras, triplex forming oligonucleotides, decoy RNAs, dsRNAs, siRNAs, aptamers, or antisense nucleic acids containing nucleic acid cleaving chemical groups, peptides, polypeptides, proteins, carbohydrates, steroids, metals and small molecules, thereby facilitating cellular uptake of such molecules.

  本发明涉及一种透过性增强剂分子，及其方法，用于增加诸如核酸、多核酸、寡核酸、酶核酸分子、反义核酸分子、2-5A反义嵌合体、三链形成寡核酸、诱饵RNA、双链RNA、小干扰RNA、适配体或含有核酸切割化学基团的核酸、肽、多肽、蛋白质、碳水化合物、类固醇、金属和小分子等不同分子的膜透过性，从而促进细胞对这些分子的摄取。
• [EN] siRNAs WITH AT LEAST TWO LIGANDS AT DIFFERENT ENDS<br/>[FR] ARNSI POSSÉDANT AU MOINS DEUX LIGANDS À DEUX EXTRÉMITÉS DISTINCTES
  申请人：SILENCE THERAPEUTICS GMBH

  公开号：WO2019193189A1

  公开（公告）日：2019-10-10

  There is provided inter alia a conjugate for inhibiting expression of a target gene in a cell, said conjugate comprising a nucleic acid portion and ligand portions, said nucleic acid portion comprising at least one duplex region that comprises at least a portion of a first RNA strand and at least a portion of a second RNA strand that is at least partially complementary to the first strand, wherein said first strand is at least partially complementary to at least a portion of RNA transcribed from said target gene, said ligand portions comprising a linker moiety and a targeting ligand for in vivo targeting of cells and being conjugated exclusively to the 3' and/or 5' ends of one or both RNA strands, wherein the 5' end of the first RNA strand is not conjugated, wherein: (i) the second RNA strand is conjugated at the 5' end to the targeting ligand, and wherein (a) the second RNA strand is also conjugated at the 3' end to the targeting ligand and the 3' end of the first RNA strand is not conjugated; or (b) the first RNA strand is conjugated at the 3' end to the targeting ligand and the 3' end of the second RNA strand is not conjugated; or (c) both the second RNA strand and the first RNA strand are also conjugated at the 3' ends to the targeting ligand; or (ii) both the second RNA strand and the first RNA strand are conjugated at the 3' ends to the targeting ligand and the 5' end of the second RNA strand is not conjugated.

  提供了一种用于抑制细胞中靶基因表达的共轭物，该共轭物包括核酸部分和配体部分，所述核酸部分包括至少一个双链区域，该区域包括至少部分第一RNA链和至少部分第二RNA链，该第二RNA链至少部分与第一链互补，其中所述第一链至少部分与从所述靶基因转录的RNA的至少部分互补，所述配体部分包括连接子基团和用于体内细胞靶向的靶向配体，并且仅连接到一个或两个RNA链的3'和/或5'末端，其中第一RNA链的5'末端未连接，其中：(i) 第二RNA链在5'末端连接到靶向配体，其中(a) 第二RNA链还在3'末端连接到靶向配体，且第一RNA链的3'末端未连接；或(b) 第一RNA链在3'末端连接到靶向配体，且第二RNA链的3'末端未连接；或(c) 第二RNA链和第一RNA链的3'末端均连接到靶向配体；或(ii) 第二RNA链和第一RNA链的3'末端均连接到靶向配体，且第二RNA链的5'末端未连接。
• [EN] LIGAND-MODIFIED DOUBLE-STRANDED NUCLEIC ACIDS<br/>[FR] ACIDES NUCLÉIQUES DOUBLE BRIN MODIFIÉS PAR UN LIGAND
  申请人：DICERNA PHARMACEUTICALS INC

  公开号：WO2016100401A1

  公开（公告）日：2016-06-23

  The invention provides for double stranded nucleic acid molecules comprising a 5 'extension of the sense or antisense strand and further comprising a plurality of nucleotides that are conjugated to a ligand and methods of using the double-stranded nucleic acid molecules. Ligand-modified oligomers where the sense stands form a tetraloop provide new potent and stable RNA interference agents. These dsNA molecules are synthesized using a plurality of nucleotides that include ligand-modified monomers, nucleotide analog monomers, modified nucleotide monomers and the like, using standard nucleotide synthetic methods and systems.

  该发明提供了包括具有感链或反义链的5'延伸以及进一步包括与配体结合的多个核苷酸的双链核酸分子，以及使用这些双链核酸分子的方法。其中，感链形成四环的配体修饰寡聚物提供了新的强效和稳定的RNA干扰剂。这些双链核酸分子是使用包括配体修饰单体、核苷酸类似物单体、修饰核苷酸单体等的多个核苷酸合成的，使用标准的核苷酸合成方法和系统。