5'-O-(dimethoxytrityl)-2'-O-(hexylamino)uridine | 165381-00-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 5'-O-(dimethoxytrityl)-2'-O-(hexylamino)uridine
• 英文别名: 1-[(2R,3R,4R,5R)-3-(6-aminohexoxy)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]pyrimidine-2,4-dione
• CAS: 165381-00-0
• 化学式: C₃₆H₄₃N₃O₈
• 分子量: 645.753
• InChiKey: VDRCZHSBSJCGSG-DWNQJFHRSA-N

物化性质

• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  47
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  142
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5'-O-(dimethoxytrityl)-2'-O-(hexylamino)uridine 在 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 5'-O-(4,4'-dimethoxytrityl)-2'-O-(6-trifluoroacetamido)hexyluridine-3'-O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite
  参考文献：
  名称：

  DELIVERY OF OLIGONUCLEOTIDES TO THE STRIATUM

  摘要：

  本发明的一个方面涉及双链iRNA剂，包括一个与目标基因互补的反义链;一个与该反义链互补的正义链;以及一个或多个脂溶性基团，通过连接物或载体与至少一条链上的一个或多个内部位置结合，从而实现对中枢神经系统组织和细胞，特别是纹状体的靶向和摄取。本发明的另一个方面涉及一种在中枢神经系统组织和细胞，特别是纹状体中基因沉默的方法，包括向需要治疗的组织/细胞或受试者中注射足够疗效量的脂溶性基团结合的双链iRNA。

  公开号：

  US20220307024A1
• 作为产物：
  描述：

  4,4'-双甲氧基三苯甲基氯 在 肼 作用下， 以 甲醇 为溶剂， 生成 5'-O-(dimethoxytrityl)-2'-O-(hexylamino)uridine
  参考文献：
  名称：

  Base-Sequence Dependence of Emission Lifetimes for D141018-30-6NA Oligomers and Duplexes Covalently Labeled with Pyrene: Relative Electron-Transfer Quenching Efficiencies of A, G, C, and T Nucleosides toward Pyrene

  摘要：

  This paper reports both continuous and time-resolved spectroscopic studies of the emission properties of photoexcited pyrene labels covalently attached to uridine nucleosides and oligonucleotides. For all nucleic acid systems, uridine is substituted with pyrene at the 2'-oxygen position, 2'-O-[hexyl-N-(1-pyrenepropylcarbonyl)amino]uridine, U(12)*. Three types of nucleic acid systems are investigated: the 5'-OH (1) and the 5'-ODMT (2) substituted U(12)*-nucleosides; four pentameric oligonucleotides, X(2)U(12)*X(2), where X is 2'-deoxyadenosine (A), 2'-deoxyguanosine (G), 2'-deoxythymidine (T), or 2'-deoxycytidine (C); and four duplexes with 18 base pairs each containing one strand with a central U(12)* label. The central U(12)* label in the duplexes has the following flanking base-sequences, 5'-... AX(2)U(12)*X(2)A ... 3', where X is A, G, T, or C. The 400-nm region emission kinetics for the four U(12)*-labeled pentamers establish the following order of pyrene*-quenching reactivities by flanking DNA bases: A < G < T < C. This ordering of reactivities is generally consistent with expected reactivites based on estimates of the free energies of pyrene* quenching by electron transfer, Delta G degrees(ET), to or from flanking DNA bases. Emission spectra and lifetimes in the 495-mn region for both U(12)*-labeled pentamers and duplexes provide direct evidence for the formation and decay of the pyrene(.+)/U(12)(.-) charge-transfer (CT) product. In general ca. 20% of the amplitude of the CT emission decays in the 1-7 ns time range and 70-80% of its amplitude decays in less than or equal to 0.2 ns. The C2U(12)*C-2 pentamer has uniquely short pi,pi* emission decay with its longest emission-lifetime component lasting only 5.6 ns and its average emission lifetime less than or equal to 0.6 ns. (In contrast the longest pi,pi* emission components for pyrene butanoic acid (PBA) and U(12)*OH (1) in methanol last, respectively, 231 and 37 ns.) Finally, the longest pi,pi* emission lifetimes of U(12)*-labeled DNA duplexes exceed those of the corresponding pentamers. A measure of duplex-induced restricted access of pyrene* to base-paired nucleosides in double-strand (ds) versus single-strand(ss) DNA can be obtained by noting that the average pi,pi* emission lifetimes (for greater than 1 ns components) lengthen 3-fold on going from the T2U(12)*T-2 pentamer to the corresponding ... AT(2)U(12)*T(2)A .... duplex and 9-fold on going from the C2U(12)*C-2 pentamer to the ... AC(2)U(12)*C(2)A ... duplex.

  DOI：

  10.1021/j100048a024

文献信息

• EXTRAHEPATIC DELIVERY
  申请人：ALNYLAM PHARMACEUTICALS, INC.

  公开号：US20220125823A1

  公开（公告）日：2022-04-28

  The invention relates to a method of gene silencing, comprising administering to a cell or a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs at one or more internal positions on at least one strand, optionally via a linker or carrier.

  本发明涉及一种基因沉默方法，包括向细胞或需要治疗的受体中给予脂溶性基团偶联的双链iRNA，在至少一条链的一个或多个内部位置上给予治疗有效量，可选地通过连接剂或载体给予。
• [EN] EXTRAHEPATIC DELIVERY<br/>[FR] ADMINISTRATION EXTRA-HÉPATIQUE
  申请人：ALNYLAM PHARMACEUTICALS INC

  公开号：WO2021092371A3

  公开（公告）日：2021-06-17
• [EN] TRANSTHYRETIN (TTR) IRNA COMPOSITIONS AND METHODS OF USE THEREOF FOR TREATING OR PREVENTING TTR-ASSOCIATED OCULAR DISEASES<br/>[FR] COMPOSITION D'ARNI DE LA TRANSTHYRÉTINE (TTR) ET SES PROCÉDÉS D'UTILISATION POUR LE TRAITEMENT OU LA PRÉVENTION DE MALADIES OCULAIRES ASSOCIÉES À TTR
  申请人：ALNYLAM PHARMACEUTICALS INC

  公开号：WO2021092145A8

  公开（公告）日：2021-07-08
• Structural modifications of antisense oligonucleotides
  作者：Ernst Urban、Christian R. Noe

  DOI：10.1016/s0014-827x(03)00022-3

  日期：2003.3

  Antisense oligonucleotides are efficient tools for the inhibition of gene expression in a sequence specific way. Natural oligonucleotides are decomposed rapidly in biological systems, which strongly restrict their application. In contrast, artificial oligonucleotides are designed to be more stable against degradation than the target mRNA, which results in a catalytic effect of the drug. Modification of the phosphate linkage has been the first successful strategy for antisense drug developments and Fomivirsene the first antisense drug in therapy. The launch of Fomivirsene has resulted in a revolutionary spin off to antisense research leading to a second generation of antisense oligonucleotides, which are stable against oligonucleotide cleaving enzymes. Among these, oligonucleotides bearing an alkoxy substituent in position 2' were the most successful ones. The third generation of antisense oligonucleotides contains structure elements, which enhance the antisense action. Zwitterionic oligonucleotides show remarkable results, first, because the stability against ribozymes is largely increased, and secondly, because the electrostatic repulsion between the anionic sense and the zwitterionic antisense cords is minimized. Promising new target molecules in antisense research are oligonucleotide chimäres, which enhance the antisense action (chimäres with intercalators, chelators or polyamines) or enable an application as sequence specific detectors (chimäres with biotin, fluorescein or radioligands).
• Lipidic nucleic acids
  作者：Muthiah Manoharan、Kathleen L. Tivel、P.Dan Cook

  DOI：10.1016/0040-4039(95)00597-6

  日期：1995.5

  Lipophilic nucleosides were synthesized from uridine via either a 2'-O-hexylamino tether or the corresponding 3'-linker. These synthons allowed site-specific incorporation of the lipophilic moieties into antisense oligonucleotides. A spectrum of lipophilicity was observed in the oligonucleotides, depending on the pendent group.