6′-aminohexyl-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-galactoside | 153252-07-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6′-aminohexyl-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-galactoside
• 英文别名: 6'-aminohexyl 2-acetamio-3,4,6-tri-O-acetyl-2-deoxy-β-D-galactopyranoside；[(2R,3R,4R,5R,6R)-5-acetamido-3,4-diacetyloxy-6-(6-aminohexoxy)oxan-2-yl]methyl acetate
• CAS: 153252-07-4
• 化学式: C₂₀H₃₄N₂O₉
• 分子量: 446.498
• InChiKey: CHKALUAMOKVWPY-OUUBHVDSSA-N

物化性质

• 沸点：
  595.0±50.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  31
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  153
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6′-aminohexyl-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-galactoside 在 palladium hydroxide, 20 wt% on carbon 、 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 生成
  参考文献：
  名称：

  Comprehensive Structure–Activity Relationship of Triantennary N-Acetylgalactosamine Conjugated Antisense Oligonucleotides for Targeted Delivery to Hepatocytes

  摘要：

  The comprehensive structure activity relation ships of triantennary GalNAc conjugated ASOs for enhancing potency via ASGR mediated delivery to hepatocytes is reported. Seventeen GalNAc clusters were assembled from six distinct scaffolds and attached to ASOs. The resulting ASO conjugates were evaluated in ASGR binding assays, in primary hepatocytes, and in mice. Five structurally distinct GalAc clusters were chosen for more extensive evaluation using ASOs targeting SRB-1, A1AT, FXI, TTR, and ApoC III mRNAs. GaINAc ASO conjugates exhibited excellent potencies (ED50 0.5-2 mg/kg) for reducing the targeted mRNAs and proteins. This work culminated in the identification of a simplified tris-based GaINAc cluster (THA-GN3), which can be efficiently assembled using readily available starting materials and conjugated to ASOs using a solution phase conjugation strategy. GalNAc ASO conjugates thus represent a viable approach for enhancing potency of ASO drugs in the clinic clinic without adding significant complexity or cost to existing protocols for manufacturing oligonucleotide drugs.

  DOI：

  10.1021/acs.jmedchem.5b01948
• 作为产物：
  描述：

  5H-吡喃并[3,2-d]噁唑-5-甲醇,6,7-二(乙酰氧基)-3a,6,7,7a-四氢-2-甲基-,乙酸酯(ester) 在 三氟甲磺酸三甲基硅酯 、 10 wt% Pd(OH)2 on carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 12.0h， 生成 6′-aminohexyl-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-galactoside
  参考文献：
  名称：

  [EN] CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE
  [FR] COMPOSÉS ANTISENS CONJUGUÉS ET LEUR UTILISATION

  摘要：

  本文提供了具有共轭基团的寡聚化合物。在某些实施例中，这些寡聚化合物与N-乙酰半乳糖结合。

  公开号：

  WO2014179620A1

文献信息

• [EN] TARGETED THERAPEUTIC NUCLEOSIDES AND THEIR USE<br/>[FR] NUCLÉOSIDES THÉRAPEUTIQUES CIBLÉES ET LEUR UTILISATION
  申请人：ISIS PHARMACEUTICALS INC

  公开号：WO2015042447A1

  公开（公告）日：2015-03-26

  Provided herein are compounds comprising one or more therapeutic nucleosides and one or more targeting groups. In certain embodiments, the compounds further comprise one or more oligonucleotides. In certain embodiments, a targeting group comprises one or more N-Acetylgalactosamine.

  本文提供的化合物包括一个或多个治疗性核苷和一个或多个靶向基团。在某些实施例中，这些化合物进一步包括一个或多个寡核苷酸。在某些实施例中，一个靶向基团包括一个或多个N-乙酰半乳糖胺。
• BIFUNCTIONAL COMPOUND WITH MONOSACCHARIDE AND N2S2 LIGAND, AND PREPARATION AND USE THEREOF
  申请人：LIU SHOW-WEN

  公开号：US20120009669A1

  公开（公告）日：2012-01-12

  A bifunctional compound with a monosaccharide and a N 2 S 2 ligand, and more particularly, a bifunctional compound with a N 2 S 2 ligand and aminohexylacetyl galactosamine (ah-GalNAc 4 ) is provided. A method for preparing the bifunctional compound with a monosaccharide and a N 2 S 2 ligand is also provided, including activating a carboxyl group in an organic ligand, reacting the activated carboxyl group with a galactopyranoside through amidation, and then hydrolyzing. The bifunctional compound of the present invention is widely useful in nuclear medicine for preparation of liver imaging agents for assisting in correct diagnosis of diseases.

  提供了一种具有单糖和N2S2配体的双功能化合物，更具体地说，提供了一种具有N2S2配体和氨基己酰半乳糖胺（ah-GalNAc4）的双功能化合物。还提供了一种制备具有单糖和N2S2配体的双功能化合物的方法，包括激活有机配体中的羧基，通过酰胺化将激活的羧基与半乳糖苷反应，然后水解。本发明的双功能化合物在核医学中广泛用于制备肝脏成像剂，以帮助正确诊断疾病。
• PRECURSOR USED FOR LABELING HEPATORCYTE RECEPTOR AND CONTAINING TRISACCHARIDE AND DIAMIDE DEMERCAPTIDE LIGAND, METHOD FOR PREPARING THE SAME, RADIOTRACER AND PHARMACEUTICAL COMPOSITION OF THE SAME
  申请人：LIU SHOW-WEN

  公开号：US20140031533A1

  公开（公告）日：2014-01-30

  A precursor used for labeling hepatocyte receptors and applied to radiotracers for imaging or pharmaceutical compositions for liver cancers is revealed. The precursor is a bifunctional compound. The bifunctional group includes a trisaccharide structure and a diamide dimercaptide (N 2 S 2 ) ligand. The trisaccharide has high affinity to asialoglycoprotein receptors (ASGPR) on surfaces of hepatocytes while N 2 S 2 ligand reacts with radioisotopes to form neutral complexes. Thus the precursor stays on surfaces of hepatocytes to provide radioisotope labeling or treatment effect of liver cancers.

  一种用于标记肝细胞受体并应用于用于肝癌成像或药物组合物的放射示踪剂的前体被揭示。该前体是一种双功能化合物。双功能基团包括三糖结构和二酰胺二巯基（N2S2）配体。三糖具有高亲和力，能与肝细胞表面的非糖蛋白受体（ASGPR）结合，而N2S2配体与放射性同位素反应形成中性络合物。因此，前体停留在肝细胞表面，提供放射同位素标记或治疗肝癌的效果。
• [EN] COMPOSITIONS AND METHODS FOR ENHANCED INTESTINAL ABSORPTION OF CONJUGATED OLIGOMERIC COMPOUNDS<br/>[FR] COMPOSITIONS ET MÉTHODES ASSURANT UNE MEILLEURE ABSORPTION INTESTINALE DE COMPOSÉS OLIGOMÈRES CONJUGUÉS
  申请人：ISIS PHARMACEUTICALS INC

  公开号：WO2015188194A1

  公开（公告）日：2015-12-10

  Provided herein are compositions and methods for non-parenteral delivery of conjugated oligomeric compounds. In certain embodiments, compositions and methods are provided for oral delivery of conjugated oligomeric compounds. In certain embodiments, the oligomeric compounds are conjugated to one or more N-acetylgalactosamines or N-acetylgalactosamine analogues.

  本文提供了用于非肠内递送共轭寡聚化合物的组合物和方法。在某些实施方式中，提供了用于口服递送共轭寡聚化合物的组合物和方法。在某些实施方式中，这些寡聚化合物与一个或多个N-乙酰半乳糖胺或N-乙酰半乳糖胺类似物共轭。
• Synthesis and biological evaluation of novel mono- and bivalent ASGP-R-targeted drug-conjugates
  作者：Rostislav A. Petrov、Svetlana Yu. Maklakova、Yan A. Ivanenkov、Stanislav A. Petrov、Olga V. Sergeeva、Emil Yu. Yamansarov、Irina V. Saltykova、Igor I. Kireev、Irina B. Alieva、Ekaterina V. Deyneka、Alina A. Sofronova、Anastasiia V. Aladinskaia、Alexandre V. Trofimenko、Renat S. Yamidanov、Sergey V. Kovalev、Victor E. Kotelianski、Timofey S. Zatsepin、Elena K. Beloglazkina、Alexander G. Majouga

  DOI：10.1016/j.bmcl.2017.12.032

  日期：2018.2

  Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent

  去唾液酸糖蛋白受体（ASGP-R）是一种有前途的生物靶标，可以将药物传递到肝癌细胞中。然而，仅有很少的实例配备有用于治疗肝细胞癌（HCC）的治疗剂的ASGP-R选择性配体的小分子缀合物。在当前的工作中，我们描述了一种方便且通用的合成方法，用于合成含有N-乙酰基-2-脱氧-2-氨基半乳糖吡喃糖和抗癌药–紫杉醇（PTX）的新型单价和多价药物结合物。几种分子已证明对ASGP-R具有高度亲和力，并且在生理条件下具有良好的稳定性，在体外具有重要意义与PTX相当的抗癌活性，以及​​通过ASGP-R介导的内吞作用具有良好的内在化。因此，具有最高效力的缀合物可以被认为是针对HCC的有前途的治疗选择。