non-phosphorous | 1134031-93-8

• 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: non-phosphorous
• 英文别名: N³-benzyloxymethyl-2'-O-methyl-3'-O-tert-butyldimethylsilyluridine；1-[(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)-3-methoxyoxolan-2-yl]-3-(phenylmethoxymethyl)pyrimidine-2,4-dione
• CAS: 1134031-93-8
• 化学式: C₂₄H₃₆N₂O₇Si
• 分子量: 492.645
• InChiKey: IZCFGSFDYNCXDN-ZHHKINOHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.48
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  97.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  non-phosphorous 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 以100%的产率得到1-((2R,3R,4R,5R)-4-((tert-butyldimethylsilyl)oxy)-5-(hydroxymethyl)-3-methoxy-tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Synthetic Studies towards the Identification of Novel Capuramycin Analogs with Mycobactericidal Activity

  摘要：

  Expeditious syntheses of capuramycin, an effective MraY inhibitor in vivo, analogs are described. Synthetic schemes reported here are extremely useful for the generation of capuramycin analogs to identify minimum structure requirement to exhibit antimycobactericidal activity.

  DOI：

  10.3987/com-08-s(f)38
• 作为产物：
  描述：

  1-[(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-methoxyoxolan-2-yl]-3-(phenylmethoxymethyl)pyrimidine-2,4-dione 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 non-phosphorous
  参考文献：
  名称：

  Synthetic Studies towards the Identification of Novel Capuramycin Analogs with Mycobactericidal Activity

  摘要：

  Expeditious syntheses of capuramycin, an effective MraY inhibitor in vivo, analogs are described. Synthetic schemes reported here are extremely useful for the generation of capuramycin analogs to identify minimum structure requirement to exhibit antimycobactericidal activity.

  DOI：

  10.3987/com-08-s(f)38

文献信息

• [EN] MODIFIED DOUBLE-STRANDED RNA AGENTS<br/>[FR] AGENTS D'ARN DOUBLE BRIN MODIFIÉ
  申请人：ALNYLAM PHARMACEUTICALS INC

  公开号：WO2016028649A1

  公开（公告）日：2016-02-25

  One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The sense strand of the dsRNA agent comprises at least one thermally destabilizing nucleotide, and at least one said thermally destabilizing nucleotide occurring at a site opposite to the seed region (positions 2-8) of the antisense strand; and the antisense strand of the dsRNA agent comprises at least two modified nucleotides that provide the nucleotide a steric bulk that is less than or equal to the steric bulk of a 2'-OMe modification, wherein said modified nucleotides are separated by 11 nucleotides in length. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

  本发明的一个方面涉及能够抑制靶基因表达的双链RNA（dsRNA）试剂。dsRNA试剂的sense链包含至少一个热不稳定核苷酸，并且至少一个该热不稳定核苷酸出现在与antisense链的seed区域（位置2-8）相对的位置上；dsRNA试剂的antisense链包含至少两个修饰核苷酸，这些核苷酸提供的立体体积小于或等于2'-OMe修饰的立体体积，其中这些修饰的核苷酸相隔11个核苷酸长度。该发明的其他方面涉及包含这些dsRNA试剂的药物组合物，适用于治疗用途，并通过给予这些dsRNA试剂的方法来抑制靶基因的表达，例如用于治疗各种疾病条件。
• 5′-<i>C</i>-Malonyl RNA: Small Interfering RNAs Modified with 5′-Monophosphate Bioisostere Demonstrate Gene Silencing Activity
  作者：Ivan Zlatev、Donald J. Foster、Jingxuan Liu、Klaus Charisse、Benjamin Brigham、Rubina G. Parmar、Vasant Jadhav、Martin A. Maier、Kallanthottathil G. Rajeev、Martin Egli、Muthiah Manoharan

  DOI：10.1021/acschembio.5b00654

  日期：2016.4.15

  metabolically stable 5′-phosphate mimics can lead to higher metabolic stability, increased RISC loading, and higher gene silencing activities of chemically modified siRNAs. In this study, we report the synthesis of 5′-C-malonyl RNA, a 5′-monophosphate bioisostere. A 5′-C-malonyl-modified nucleotide was incorporated at the 5′-terminus of chemically modified RNA oligonucleotides using solid-phase synthesis

  5'-磷酸化是事件级联过程中的关键步骤，该事件导致将小的干扰RNA（siRNA）加载到RNA诱导的沉默复合体（RISC）中以引发基因沉默。外源性siRNA的5'-磷酸化通常是通过胞质Clp1激酶完成的，在大多数情况下，合成siRNA上5'-单磷酸的存在并不是活性的先决条件。化学上引入的，代谢稳定的5'-磷酸酯模拟物可以导致更高的代谢稳定性，增加的RISC负载以及化学修饰的siRNA的更高的基因沉默活性。在这项研究中，我们报告5'- C-丙二酰RNA，一种5'-单磷酸酯的生物等排体的合成。5′-碳使用固相合成在化学修饰的RNA寡核苷酸的5'-末端掺入了-丙二酰基修饰的核苷酸。体外沉默活性，体外代谢稳定性，并且在体外RISC 5'-装载Ç -malonyl的siRNA相比相应5'-磷酸化和5'-未磷酸化的siRNA。5'- C-丙二酰基siRNA显示出持续或改善的体外基因沉默和高水平的Ago2
• 5'-END DERIVATIVES
  申请人：Manoharan Muthiah

  公开号：US20130323836A1

  公开（公告）日：2013-12-05

  The present invention provides compounds of formula (1). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene.

  本发明提供了式（1）的化合物。发明的另一个方面涉及抑制细胞中基因表达的方法，该方法包括（a）将本发明的寡核苷酸与细胞接触；以及（b）维持从步骤（a）中的细胞足够时间以获得目标基因mRNA的降解。