12-amino-N-((2S,3S,4R)-3,4-dihydroxy-1-((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-tetrahydro-2H-pyran-2-yloxy)octadecan-2-yl)dodecanamide | 229625-94-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 鞘脂
• 英文名称: 12-amino-N-((2S,3S,4R)-3,4-dihydroxy-1-((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-tetrahydro-2H-pyran-2-yloxy)octadecan-2-yl)dodecanamide
• CAS: 229625-94-9
• 化学式: C₃₆H₇₂N₂O₉
• 分子量: 676.976
• InChiKey: MGCBGIOYMOXWEQ-QNAIHFNASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.96
• 重原子数：
  47.0
• 可旋转键数：
  31.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  194.96
• 氢给体数：
  8.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  12-amino-N-((2S,3S,4R)-3,4-dihydroxy-1-((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-tetrahydro-2H-pyran-2-yloxy)octadecan-2-yl)dodecanamide 、 十三酸 在 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 N-(12-(((2S,3S,4R)-3,4-dihydroxy-1-(((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)octadecan-2-yl)amino)-12-oxododecyl)tridecanamide
  参考文献：
  名称：

  CD1d糖脂配体对自然杀伤性T细胞的有效Th2细胞因子偏倚：脂质组分中极性基团的锚定作用

  摘要：

  具有偏向性的CD1d配体是佐剂和治疗药物的潜在诱人候选物。然而，有效配体的数量是有限的，并且它们的偏置机制仍然不清楚。在本文中，基于脂质部分的修饰，已经鉴定出一系列新颖的偏于Th2的CD1d糖脂配体。这些已经显示出高结合亲和力和有效的Th2细胞因子产生。重要的是，含有截短的酰基链的变体仍保留其结合亲和力和激动活性，这可能与“锚定效应”相关，即在酰基链上的极性基团与CD1d脂质之间形成了掩埋的氢键。装订袋。分析表明，配体– CD1d复合物在细胞表面的出现率与Th2偏向反应有关。设计的配体

  DOI：

  10.1002/anie.201802983
• 作为产物：
  描述：

  12-(2,2,2-trifluoroacetamido)dodecanoic acid 在 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 12-amino-N-((2S,3S,4R)-3,4-dihydroxy-1-((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-tetrahydro-2H-pyran-2-yloxy)octadecan-2-yl)dodecanamide
  参考文献：
  名称：

  Synthesis of NBD-α-galactosylceramide and Its Immunologic Properties

  摘要：

  [GRAPHICS]A representative alpha-galactosylceramide (alpha-GalCer), KRN7000, can activate NKT cells through CD1d molecules, which play an essential role in the generation of the strong antitumor activity of KRN7000, Our previous study has demonstrated that alpha-GalCer binds directly to CD1d molecules. However, it is controversial whether Cold binds a-GalCer in endosomal compartments, To address this question, we synthesized NBD-alpha-GalCer, which has strong fluorescent properties. We found that the NBD-alpha-GalCer has immunostimulatory activity that is stronger than that of KRN7000.

  DOI：

  10.1021/ol9900111

文献信息

• COMPOUND OR SALT THEREOF, NATURAL KILLER T CELL ACTIVATOR, AND PHARMACEUTICAL COMPOSITION
  申请人：KEIO UNIVERSITY

  公开号：US20200207798A1

  公开（公告）日：2020-07-02

  The invention provides a compound or a salt thereof capable of activating natural killer T cell, a natural killer T cell activating agent containing such a compound or a salt thereof, and a pharmaceutical composition. The compound of the invention is a compound represented by the following formula (1) or a salt thereof. It is preferable that total carbon number of the number of carbon atoms in the monovalent hydrocarbon group in R 1 in the formula (1) excluding a substitutent and the number of carbon atoms in the divalent hydrocarbon group in X 1 is 5 to 50. The natural killer T cell activating agent contains the aforementioned compound or a salt thereof. The pharmaceutical composition contains the aforementioned compound or a pharmacologically acceptable salt thereof.

  该发明提供了一种能够激活自然杀伤T细胞的化合物或其盐，包含这种化合物或其盐的自然杀伤T细胞激活剂，以及一种药物组合物。该发明的化合物是由以下式（1）表示的化合物或其盐。最好的情况是，在式（1）中R1中的单价碳氢化合物基中的碳原子数（不包括取代基）和X1中的双价碳氢化合物基中的碳原子数总和为5至50。自然杀伤T细胞激活剂含有上述化合物或其盐。药物组合物含有上述化合物或其药理学上可接受的盐。
• Design and Discovery of Covalent α-GalCer Derivatives as Potent CD1d Ligands
  作者：Junichiro Kishi、Shinsuke Inuki、Emi Kashiwabara、Takehiro Suzuki、Naoshi Dohmae、Yukari Fujimoto

  DOI：10.1021/acschembio.9b00700

  日期：2020.2.21

  CD1d is a nonpolymorphic antigen-presenting protein responsible for the regulation of natural killer T (NKT) cell activation. alpha-Galactosyl ceramide (alpha-GalCer, KRN7000) is the representative CD1d ligand that can bind to the CD1d protein. The resulting complex is recognized by the T cell receptors of the NKT cell, inducing various immune responses. Previous structure-activity relationship studies of alpha-GalCer have revealed that the ability of NKT cells to induce cytokines depends on the ligand structure, and in particular, ligands that form more stable complexes with CD1d display potent activity. We focused on the Cys residue of the large hydrophobic pockets of CD1d (A' pocket) and developed alpha-GalCer derivatives containing groups that can form covalent bonds. The assay results revealed that these ligands displayed higher levels of cytokine production and Th2 cell-type cytokine polarization response. Furthermore, the LC-MS/MS analysis indicated that the chloroacetylamide-containing ligand was covalently bound to Cys12 of CD1d, which suggests that the enhanced activities result from the formation of a stable CD1d-ligand complex. To our knowledge, this is the first ligand that allows covalent bond formation to CD1d under physiological conditions.