2'-O-phenoxycarbonyl-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)uridine | 1192821-14-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2'-O-phenoxycarbonyl-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)uridine
• CAS: 1192821-14-9
• 化学式: C₂₈H₄₂N₂O₉Si₂
• 分子量: 606.82
• InChiKey: YTZWIMGRWNFZTH-VNSJUHMKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.97
• 重原子数：
  41.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  127.31
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  2'-O-phenoxycarbonyl-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)uridine 在 吡啶 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 14.0h， 生成 (2R,3R,4R,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-hydroxytetrahydrofuran-3-yl (4-(2,2,2-trifluoroacetamido)butyl)carbamate
  参考文献：
  名称：

  阳离子2'- O- [ N-（4-氨基丁基）氨基甲酰基]修饰的寡核苷酸的合成与性能

  摘要：

  合成了2'- O- [ N-（4-氨基丁基氨基甲酰基）]尿苷（U abcm），并将其掺入寡核苷酸中。掺入U abcm的寡核苷酸与包含2'- O-氨基甲酰基尿苷（U cm）的寡核苷酸形成互补和错配的RNA，形成更稳定的双链体。具有U abcm -rG碱基对的双链体的稳定性显示出比具有未修饰的U-rG碱基对的双链体更高的热稳定性。U abcm残基显示出对蛇毒磷酸二酯酶的增强抗性。

  DOI：

  10.1016/j.bmcl.2012.02.012
• 作为产物：
  描述：

  氯甲酸苯酯 、 3',5'-O-(1,1,3,3-四异丙基-1,3-二硅氧烷)尿苷 在 吡啶 作用下， 反应 3.0h， 生成 2'-O-phenoxycarbonyl-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)uridine
  参考文献：
  名称：

  阳离子2'- O- [ N-（4-氨基丁基）氨基甲酰基]修饰的寡核苷酸的合成与性能

  摘要：

  合成了2'- O- [ N-（4-氨基丁基氨基甲酰基）]尿苷（U abcm），并将其掺入寡核苷酸中。掺入U abcm的寡核苷酸与包含2'- O-氨基甲酰基尿苷（U cm）的寡核苷酸形成互补和错配的RNA，形成更稳定的双链体。具有U abcm -rG碱基对的双链体的稳定性显示出比具有未修饰的U-rG碱基对的双链体更高的热稳定性。U abcm残基显示出对蛇毒磷酸二酯酶的增强抗性。

  DOI：

  10.1016/j.bmcl.2012.02.012

文献信息

• Synthesis and hybridization of 2′-O-methyl-RNAs incorporating 2′-O-carbamoyluridine and unique participation of the carbamoyl group in U–G base pair
  作者：Kohji Seio、Ryuya Tawarada、Takeshi Sasami、Masashi Serizawa、Misako Ise、Akihiro Ohkubo、Mitsuo Sekine

  DOI：10.1016/j.bmc.2009.08.053

  日期：2009.10

  2'-O-Carbamoyluridine (U-cm) was synthesized and incorporated into DNAs and 2,-O-Me-RNAs. The oligonucleotides incorporating U-cm formed less stable duplexes with their complementary and U-cm-U, U-cm-C single-base mismatched DNAs and RNAs in comparison with those without the carbamoyl group. On the contrary, the T-m analyses revealed that the duplexes with a mismatched U-cm-G base pair showed almost the same thermostability as the corresponding unmodified duplexes. Molecular dynamics (MD) simulations of the U-cm-modified 2'-O-Me-RNA/RNA duplexes with U-cm-G mismatched base pair suggested that the carbamoyl group could participate in the U-cm-G base pair by an additional intermolecular hydrogen bond between the carbamoyl oxygen and the H2 of the guanine base. (C) 2009 Elsevier Ltd. All rights reserved.
• JP2015/20994
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] 2'-MODIFIED NUCLEOSIDE BASED OLIGONUCLEOTIDE PRODRUGS<br/>[FR] PROMÉDICAMENTS OLIGONUCLÉOTIDIQUES À BASE DE NUCLÉOSIDES MODIFIÉS EN 2'
  申请人：[en]ALNYLAM PHARMACEUTICALS, INC.

  公开号：WO2022147223A2

  公开（公告）日：2022-07-07

  This invention relates to an oligonucleotide comprising one or more 2'-modified nucleosides, wherein the 2'-position of the nucleoside has a structure of formula (I). The invention also relates to a pharmaceutical composition comprising the oligonucleotide described herein and a method of reducing or inhibiting the expression of a target gene by administering to the subject a therapeutically effective amount of the oligonucleotide described herein. The invention also relates to a method of bioactivating an oligonucleotide comprising one or more 2'-modified nucleosides, wherein the 2'-position of the nucleoside is modified by a bio-cleavable linking group, wherein the bio-cleavable linking group comprises acetal, disulfide, carbamate, amide, sulfonamide, a biocleavable carbohydrate linker, or combinations thereof, said method comprising the step of: exposing the oligonucleotide to a physiological condition that causes the bio-cleavable linking group to be cleaved from the 2'-modified nucleoside, thereby regenerating the 2'-OH group of the nucleoside.