[(E)-2-[(2S,4R,5R)-4-[hydroxy(methyl)phosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]ethenyl]phosphonic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: [(E)-2-[(2S,4R,5R)-4-[hydroxy(methyl)phosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]ethenyl]phosphonic acid
• 化学式: C₁₂H₁₈N₂O₈P₂S
• 分子量: 412.29
• InChiKey: RTCOUZNUCFVDOC-GGQKOLOXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  178
• 氢给体数：
  4
• 氢受体数：
  9

文献信息

• SHORT INTERFERING NUCLEIC ACID (siNA) MOLECULES CONTAINING A 2' INTERNUCLEOSIDE LINKAGE
  申请人：Chang Wonsuk

  公开号：US20160068837A1

  公开（公告）日：2016-03-10

  The present invention relates to RNAi molecules, and compositions thereof, comprising a 2′ internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5′ end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5′ modified nucleotides that comprise, among other potential modifications, a 2′ internucleoside linkage. The invention further relates to 5′ modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.

  本发明涉及RNAi分子及其组成物，包括连接在反义链5'端的位置1核苷酸和位置2核苷酸之间的2'间核苷酸连接。具体而言，本发明涉及能够介导RNA干扰的单链和双链短干扰核酸（siNA）分子，其包含5'修饰核苷酸，其中包括2'间核苷酸连接等其他潜在修饰。本发明还涉及用作试剂的5'修饰核苷酸，用于生成本发明的RNAi分子以及使用所述RNAi分子的方法。
• Dual molecular delivery of oligonucleotides and peptide containing conjugates
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10010562B2

  公开（公告）日：2018-07-03

  Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

  本文公开了一种抑制受试者基因表达的方法，包括施用(1)包含R-(L)a-(G)b的组合物；其中R是选自由DNA、RNA、siRNA和microRNA组成的组的寡核苷酸；L是连接子，且L的每个出现独立地选自表3；G是靶向配体，且G的每个出现独立地选自表4；a和b中的每一个独立地为0、1、2、3或4；和 (2)包含(P)c-(L)d-(G)e的组合物；其中P是多肽，且P的每一次出现独立地选自表2；L是连接体，L的每个出现独立地选自表3；G是靶向配体，G的每个出现独立地选自表4；d是0、1、2、3、4、5或6；c和e各自独立地为1、2、3、4、5或6。(1)和(2)中的组合物可以联合给药或顺序给药。
• Peptide containing conjugates for dual molecular delivery of oligonucleotides
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10239957B2

  公开（公告）日：2019-03-26

  Disclosed herein is a peptide containing conjugate comprising (P)c-(L)d-(G)e, wherein P is a peptide and each occurance of P is independently selected from Table 2; L is an optional linker and each occurance of L, if present, is independently selected from Table 3; G is a targeting ligand and each occurance of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. The conjugate can be administered to a subject either alone or in combination with a composition comprising R-(L)a-(G)b, wherein R is an oligonucleotide as defined herein, to inhibit expression of a gene of the subject.

  本文公开了一种含有肽的共轭物，该共轭物包含(P)c-(L)d-(G)e，其中P是肽，且P的每个出现独立地选自表2；L是任选连接体，且L的每个出现（如果存在）独立地选自表3；G是靶向配体，且G的每个出现独立地选自表4；d是0、1、2、3、4、5或6；且c和e的每个出现独立地是1、2、3、4、5或6。该共轭物可单独或与包含 R-(L)a-(G)b（其中 R 是本文定义的寡核苷酸）的组合物结合施用给受试者，以抑制受试者基因的表达。
• Short interfering nucleic acid (siNA) molecules containing a 2′ internucleoside linkage (3dT)
  申请人：SIRNA THERAPEUTICS, INC.

  公开号：US10738308B2

  公开（公告）日：2020-08-11

  The present invention relates to RNAi molecules, and compositions thereof, comprising a 2′ internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5′ end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5′ modified nucleotides that comprise, among other potential modifications, a 2′ internucleoside linkage. The invention further relates to 5′ modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.

  本发明涉及RNAi分子及其组合物，其包含连接反义链5′端的1位核苷酸和2位核苷酸的2′核苷间连接。具体地说，本发明涉及能够介导 RNA 干扰的单链和双链短干扰核酸（siNA）分子，这些分子包含 5′修饰的核苷酸，这些核苷酸除其他可能的修饰外，还包含 2′核苷间连接。本发明进一步涉及用作试剂生成本发明 RNAi 分子的 5′修饰核苷酸以及使用所公开 RNAi 分子的方法。
• SHORT INTERFERING NUCLEIC ACID (SINA) MOLECULES CONTAINING A 2' INTERNUCLEOSIDE LINKAGE
  申请人：Sirna Therapeutics, Inc.

  公开号：EP2958998B1

  公开（公告）日：2017-12-27