N-Fmoc-3R-hydroxypyrrolidine-5S-methanol | 163671-09-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-Fmoc-3R-hydroxypyrrolidine-5S-methanol
• 英文别名: (9H-Fluoren-9-yl)methyl (2S,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate；9H-fluoren-9-ylmethyl (2S,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate
• CAS: 163671-09-8
• 化学式: C₂₀H₂₁NO₄
• 分子量: 339.391
• InChiKey: SCXXARDQPGZAJU-UONOGXRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-Fmoc-3R-hydroxypyrrolidine-5S-methanol 在 哌啶 、 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 吡啶 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 {(2S,4R)-2-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-pyrrolidin-1-yl}-phenyl-methanone
  参考文献：
  名称：

  N-取代羟基脯氨醇亚磷酰胺的合成，用于制备组合文库

  摘要：

  由反式-4-羟基脯氨酸制备了一系列的N-取代的DMT-羟甲基吡咯烷醇亚磷酰胺。这些可以使用自动化合成技术以高产率和高纯度偶联，从而允许将多种功能引入磷酸二酯低聚物中。

  DOI：

  10.1016/0040-4039(94)88498-6
• 作为产物：
  描述：

  Fmoc-L-4-羟基脯氨酸 在 硼烷二甲硫醚络合物 作用下， 以 四氢呋喃 为溶剂， 生成 N-Fmoc-3R-hydroxypyrrolidine-5S-methanol
  参考文献：
  名称：

  N-取代羟基脯氨醇亚磷酰胺的合成，用于制备组合文库

  摘要：

  由反式-4-羟基脯氨酸制备了一系列的N-取代的DMT-羟甲基吡咯烷醇亚磷酰胺。这些可以使用自动化合成技术以高产率和高纯度偶联，从而允许将多种功能引入磷酸二酯低聚物中。

  DOI：

  10.1016/0040-4039(94)88498-6

文献信息

• [EN] CONJUGATES AND PREPARATION AND USE THEREOF<br/>[FR] CONJUGUÉS ET PRÉPARATION ET UTILISATION ASSOCIÉES
  申请人：SUZHOU RIBO LIFE SCIENCE CO LTD

  公开号：WO2019128611A1

  公开（公告）日：2019-07-04

  Disclosed are a compound for forming a conjugate with an active agent such as an oligonucleotide having a structure represented by Formula (321), and a corresponding conjugate. The conjugate can specifically target hepatocytes, thereby effectively solves the problems associated with delivery of oligonucleotide drugs in vivo, and has low toxicity and excellent delivery efficiency while maintaining high stability for the delivered oligonucleotide.

  揭示了一种用于与活性剂形成共轭物的化合物，例如具有由公式（321）表示的结构的寡核苷酸，并且相应的共轭物。该共轭物可以特异性地靶向肝细胞，因此有效地解决了与体内寡核苷酸药物传递相关的问题，并且在保持传递的寡核苷酸高稳定性的同时具有低毒性和出色的传递效率。
• Amine compounds and combinatorial libraries comprising same
  申请人：ISIS Pharmaceuticals, Inc.

  公开号：US06316626B1

  公开（公告）日：2001-11-13

  The present invention provides monocyclic, bicyclic and oligomeric amine compounds with at least two sites of diversity. These compounds are formed from monocyclic scaffolds which can be cyclized to form bicyclic amine scaffolds. These can then be reacted with building blocks to form the amine compounds of the invention. This invention further provides libraries or monocyclic, bicyclic and oligomeric amine compounds. Also provided are methods for preparing monocyclic, bicyclic and oligomeric amine compounds and libraries thereof. The present invention also provides pharmaceutical compositions of the monocyclic, bicyclic and oligomeric amine compounds.

  本发明提供了具有至少两个多样性位点的单环、双环和寡聚胺化合物。这些化合物由单环支架形成，可以被环化形成双环胺支架。然后可以将其与构建块反应形成本发明的胺化合物。本发明还提供了单环、双环和寡聚胺化合物的库。还提供了制备单环、双环和寡聚胺化合物及其库的方法。本发明还提供了单环、双环和寡聚胺化合物的药物组合物。
• [EN] COMPOUND HAVING LIVER-TARGETING DELIVERY EFFECT AND OLIGONUCLEOTIDE CONJUGATE THEREOF<br/>[FR] COMPOSÉ AYANT UN EFFET D'ADMINISTRATION CIBLANT LE FOIE ET CONJUGUÉ OLIGONUCLÉOTIDIQUE DE CELUI-CI<br/>[ZH] 具有肝靶向递送效应的化合物及其寡聚核苷酸缀合物
  申请人：[en]CSPC ZHONGQI PHARMACEUTICAL TECHNOLOGY (SHIJIAZHUANG) CO., LTD;[zh]石药集团中奇制药技术（石家庄）有限公司

  公开号：WO2023208106A1

  公开（公告）日：2023-11-02

  本发明提供一类式(I)所示的化合物，或其前药、互变异构体、立体异构体、溶剂化物、同位素衍生物或其药学上可接受的盐。本发明化合物是一种新型GalNAc衍生物，可与寡聚核苷酸形成式(II)的化学缀合物，该化学缀合物具有肝靶向递送效应。
• Serial incorporation of a monovalent GalNAc phosphoramidite unit into hepatocyte-targeting antisense oligonucleotides
  作者：Tsuyoshi Yamamoto、Motoki Sawamura、Fumito Wada、Mariko Harada-Shiba、Satoshi Obika

  DOI：10.1016/j.bmc.2015.11.036

  日期：2016.1

  The targeting of abundant hepatic asialoglycoprotein receptors (ASGPR) with trivalent N-acetylgalactosamine (GalNAc) is a reliable strategy for efficiently delivering antisense oligonucleotides (ASOs) to the liver. We here experimentally demonstrate the high systemic potential of the synthetically-accessible, phosphodiester-linked monovalent GalNAc unit when tethered to the 50-terminus of well-characterised 2',4'-bridged nucleic acid (also known as locked nucleic acid)-modified apolipoprotein B-targeting ASO via a bio-labile linker. Quantitative analysis of the hepatic disposition of the ASOs revealed that phosphodiester is preferable to phosphorothioate as an interunit linkage in terms of ASGPR binding of the GalNAc moiety, as well as the subcellular behavior of the ASO. The flexibility of this monomeric unit was demonstrated by attaching up to 5 GalNAc units in a serial manner and showing that knockdown activity improves as the number of GalNAc units increases. Our study suggests the structural requirements for efficient hepatocellular targeting using monovalent GalNAc and could contribute to a new molecular design for suitably modifying ASO. (C) 2015 Elsevier Ltd. All rights reserved.
• US6316626B1
  申请人：——

  公开号：US6316626B1

  公开（公告）日：2001-11-13