4-amino-1-[(2R,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidin-2-one | 838-07-3

• 物质功能分类: 生物化工 - 核苷类药物 - 脱氧核苷酸及其类似物
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 4-amino-1-[(2R,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidin-2-one
• CAS: 838-07-3
• 化学式: C₁₀H₁₅N₃O₄
• 分子量: 241.24
• InChiKey: LUCHPKXVUGJYGU-SPDVFEMOSA-N

物化性质

• 熔点：
  217-219 °C(lit.)
• 沸点：
  492.8±55.0 °C(Predicted)
• 密度：
  1?+-.0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（稍微加热）、甲醇（稍微加热）、水（稍微加热）
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 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：
  108
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2934999090
• RTECS号：
  HA3860000
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

5-Methyl-2'-deoxycytidine（简称 5-Me-dC、5-甲基脱氧胞苷或 5MedCyd）存在于大多数真核生物的DNA中。

靶点

Human Endogenous Metabolite

用途：医药中间体；核苷类

文献信息

• Protection of nucleosides
  申请人：——

  公开号：US20040158055A1

  公开（公告）日：2004-08-12

  A process of manufacturing protected nucleosides comprises reacting a nucleoside with a protecting reagent in the presence of a regioselective activator to produce a regioselectively protected nucleoside. In some embodiments of the inventive method, an optionally substituted trityl or optionally substituted pixyl group is selectively added to the 5′-O-position of a nucleoside in the presence of lutidine as activator or activator/solvent. The inventive method results in improved selectivity of the 5′-O-position over the 3′-O-position, thereby improving overall product yield and purity, and permitting simplified purification protocols, in some cases obviating the need for chromatography to produce a purified protected nucleoside suitable for automated synthesis of oligonucleotides, such as primers, probes and antisense molecules.

  制造受保护核苷的过程包括在具有区域选择性活化剂的存在下，将核苷与保护试剂反应，以产生区域选择性受保护核苷。在本发明方法的一些实施例中，可选择地将一个可选取代的三苯甲基或可选择地取代的哌啶基团选择性地添加到核苷的5'-O-位置，同时存在卢替啶作为活化剂或活化剂/溶剂。这种创新方法导致了对5'-O-位置的选择性提高，从而提高了整体产物产量和纯度，并允许简化的纯化方案，在某些情况下，无需色谱法即可生产适用于寡核苷酸的自动合成的纯化受保护核苷，例如引物、探针和反义分子。
• [EN] OLIGONUCLEOTIDE COMPOSITIONS AND METHODS THEREOF<br/>[FR] COMPOSITIONS OLIGONUCLÉOTIDIQUES ET MÉTHODES ASSOCIÉES
  申请人：WAVE LIFE SCIENCES LTD

  公开号：WO2019032612A1

  公开（公告）日：2019-02-14

  Among other things, the present disclosure provides oligonucleotides, compositions, and methods thereof. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., knockdown ability, stability, delivery, etc. In some embodiments, the oligonucleotides decrease the expression, activity and/or level of a C9orf72 gene, including but not limited to, one comprising a repeat expansion, or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in treatment of C9orf72-related disorders.

  本公开提供寡核苷酸、组合物及其方法等内容。本公开涵盖了对寡核苷酸的结构元素（如碱基序列、化学修饰（例如糖、碱基和/或核苷酸间连接的修饰）或其模式、与额外化学基团的结合以及/或立体化学[例如骨架手性中心的立体化学（手性核苷酸间连接）]及/或其模式等）的认识，这些因素可能对寡核苷酸的性质和活性（例如敲低能力、稳定性、传递等）产生重要影响。在某些实施例中，寡核苷酸降低C9orf72基因的表达、活性和/或水平，包括但不限于包含重复扩展或其基因产物的基因。在某些实施例中，本公开提供使用所提供的寡核苷酸组合物治疗疾病的方法，例如治疗C9orf72相关疾病。
• COMPOSITIONS AND METHODS FOR CHEMICAL CLEAVAGE AND DEPROTECTION OF SURFACE-BOUND OLIGONUCLEOTIDES
  申请人：Illumina, Inc.

  公开号：US20190352327A1

  公开（公告）日：2019-11-21

  Embodiments of the present disclosure relate to methods of preparation of templates for polynucleotide sequencing. In particular, the disclosure relates to linearization of clustered polynucleotides in preparation for sequencing by cleavage of one or more first strands of double-stranded polynucleotides immobilized on a solid support by a transition metal complex, for example, a palladium complex or a nickel complex. Further disclosure relate to linearization of clustered polynucleotides by cleaving one or more second strands of double double-stranded polynucleotides immobilized on a solid support comprising azobenzene linker by Na 2 S 2 O 4 . Nucleotides and oligonucleotides comprising a 3′ phosphate moiety blocking group, and methods of removing the same using a fluoride reagent are also disclosed.

  本公开的实施例涉及用于多核苷酸测序模板制备的方法。具体而言，本公开涉及通过过渡金属络合物（例如钯络合物或镍络合物）裂解固定在固体支持物上的双链多核苷酸的一条或多条第一链，以便为测序做准备。进一步公开涉及通过Na2S2O4裂解固定在含有偶氮苯联结剂的固体支持物上的双链多核苷酸的一条或多条第二链来线性化团簇化的多核苷酸。还公开了含有3'磷酸酯基团阻断基团的核苷酸和寡核苷酸，以及使用氟化试剂去除这些基团的方法。
• RADIOLABELED NUCLEOSIDE ANALOGUE, AND PREPARATION METHOD AND USE THEREOF
  申请人：WANG HSIN-ELL

  公开号：US20120178919A1

  公开（公告）日：2012-07-12

  A radiolabeled nucleoside analogue is provided, which includes radioactive iodine 123 I/ 131 I, and a nucleoside analogue selected from a group consisting of cytidine, thymidine, uridine, and a derivative thereof. A method for preparing the radiolabeled nucleoside analogue, and a use thereof are further provided. The nucleoside analogue, prepared through the preparation method with a short synthesis time and a high radiochemical yield, has a long in vivo physiological half life and a high stability in serum, and, as a radiopharmaceutical composition, is useful in development of tumor proliferation diagnosis or therapy prognosis evaluation, and further assists in observation of long-time in vivo metabolism of a drug.

  提供了一种放射性标记的核苷类似物，包括放射性碘123I/131I，以及从胞嘧啶、胸苷、尿苷和其衍生物组成的一组中选择的核苷类似物。还提供了一种制备放射性标记的核苷类似物的方法以及其用途。通过具有短合成时间和高放射化学产率的制备方法制备的核苷类似物，在体内具有长的生理半衰期和高的血清稳定性，作为一种放射性药物组合物，有助于肿瘤增殖诊断或治疗预后评估的发展，并进一步帮助观察药物的长期体内代谢。
• OLIGONUCLEOTIDE AND ARTIFICIAL NUCLEOSIDE HAVING GUANIDINE BRIDGE
  申请人：OSAKA UNIVERSITY

  公开号：US20150266917A1

  公开（公告）日：2015-09-24

  An oligonucleotide or a pharmacologically acceptable salt thereof of the present invention contains a compound represented by formula I or II or a salt thereof, and at least one of nucleoside structures represented by formula I′ or II′. According to the present invention, provided is a nucleic acid molecule for oligonucleotides having high binding affinity and specificity to a target nucleic acid, and exhibiting high nuclease resistance.

  本发明的寡核苷酸或其药理学上可接受的盐包含由式I或II表示的化合物或其盐，并且至少含有由式I'或II'表示的核苷酸结构中的一个。根据本发明，提供了一种寡核苷酸的核酸分子，具有高结合亲和力和特异性，对目标核酸具有高核酸酶抗性。