19,19,19-triphenyl-3,6,9,12,15,18-hexaoxanonadec-1-ylmethanesulfonate | 745048-16-2

• 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: 19,19,19-triphenyl-3,6,9,12,15,18-hexaoxanonadec-1-ylmethanesulfonate
• 英文别名: TrO-PEG6-OMs；2-[2-[2-[2-[2-(2-Trityloxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethyl methanesulfonate
• CAS: 745048-16-2
• 化学式: C₃₂H₄₂O₉S
• 分子量: 602.746
• InChiKey: JVQOWHDCRSMZKA-UHFFFAOYSA-N

物化性质

• 沸点：
  699.5±55.0 °C(Predicted)
• 密度：
  1.175±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  42
• 可旋转键数：
  23
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  19,19,19-triphenyl-3,6,9,12,15,18-hexaoxanonadec-1-ylmethanesulfonate 在 盐酸 、 sodium azide 、 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 17-氨基-3,6,9,12,15-五氧杂十七烷醇
  参考文献：
  名称：

  Ligand–Phospholipid Conjugation: A Versatile Strategy for Developing Long-Acting Ligands That Bind to Membrane Proteins by Restricting the Subcellular Localization of the Ligand

  摘要：

  We hypothesized that if drug localization can be restricted to a particular subcellular domain where their target proteins reside, the drugs could bind to their target proteins without being metabolized and/or excreted, which would significantly extend the half-life of the corresponding drug target complex. Thus, we designed ligand phospholipid conjugates in which the ligand is conjugated with a phospholipid through a polyethylene glycol linker to restrict the subcellular localization of the ligand in the vicinity of the lipid bilayer. Here, we present the design, synthesis, pharmacological activity, and binding mode analysis of ligand phospholipid conjugates with muscarinic acetylcholine receptors as the target proteins. These results demonstrate that ligand phospholipid conjugation can be a versatile strategy for developing long-acting ligands that bind to membrane proteins in drug discovery.

  DOI：

  10.1021/acs.jmedchem.8b00041
• 作为产物：
  描述：

  三苯基甲醇 在 potassium tert-butylate 、 对甲苯磺酸 、 三乙胺 作用下， 以 二氯甲烷 、 叔丁醇 、 苯 为溶剂， 反应 5.5h， 生成 19,19,19-triphenyl-3,6,9,12,15,18-hexaoxanonadec-1-ylmethanesulfonate
  参考文献：
  名称：

  Fluorescent Pirenzepine Derivatives as Potential Bitopic Ligands of the Human M1 Muscarinic Receptor

  摘要：

  Following a recent description of fluorescence resonance energy transfer between enhanced green fluorescent protein (EGFP)-fused human muscarinic M1 receptors and Bodipy-labeled pirenzepine, we synthesized seven fluorescent derivatives of this antagonist in order to further characterize ligand-receptor interactions. These compounds carry Bodipy [558/568], Rhodamine Red-X [560/580], or Fluorolink Cy3 [550/570] fluorophores connected to pirenzepine through various linkers. All molecules reversibly bind with high affinity to M1 receptors (radioligand and energy transfer binding experiments) provided that the linker contains more than six atoms. The energy transfer efficiency exhibits modest variations among ligands, indicating that the distance separating EGFP from the fluorophores remains almost constant. This also supports the notion that the fluorophores may bind to the receptor protein. Kinetic analyses reveal that the dissociation of two Bodipy derivatives (10 or 12 atom long linkers) is sensitive to the presence of the allosteric modulator brucine, while that of all other molecules (15-24 atom long linkers) is not. The data favor the idea that these analogues might interact with both the acetylcholine and the brucine binding domains.

  DOI：

  10.1021/jm040800a

文献信息

• [EN] CLEAVABLE LIPIDIC COMPOUNDS, COMPOSITIONS CONTAINING THEREOF, AND USES THEREOF<br/>[FR] COMPOSÉS LIPIDIQUES CLIVABLES, COMPOSITIONS LES CONTENANT ET UTILISATIONS ASSOCIÉES
  申请人：SANOFI PASTEUR

  公开号：WO2022013439A1

  公开（公告）日：2022-01-20

  The disclosure relates to novel lipidic compounds, method of manufacturing lipid nanoparticles (LNPs) containing thereof, lipid nanoparticles (LNPs) containing thereof, and the use of the LNPs for the delivery of nucleic acid. The lipidic compounds as disclosed herein is a cleavable lipidic compound comprising at least one terminal radical of formula (I): Y-(CHR)n-Z-(CHR')p-Q * (I) wherein: - * is the end linked, directly or not, to one C10 to C55 lipophilic or hydrophobic tail-group; - Y is a radical selected in the group consisting of methyl, methoxy, trifluoromethyl, imidazolyl, or is one hydrogen; - Z is a radical -NH-CH2-CO-O-** or a radical -CR''(NH2)-CO-O-** with ** that is the end closest to Q and R'' that is selected in the group consisting of hydrogen, methyl radical and trifluoromethyl radical; - Q is a radical -NH-CH2-CO-O-*** or a radical -CR''(NH2)-CO-O-*** with R'' selected in the group consisting of hydrogen, methyl radical and trifluoromethyl radical and *** that is the end linked, directly or not, to said lipophilic or hydrophobic tail-group; - R et R' are, independently one from the other, one hydrogen, one methyl radical or one trifluoromethyl radical; - n et p are independently one from the other 0, 1 or 2; or one of its pharmaceutically acceptable salts and with said compound being in all the possible racemic, enantiomeric and diastereoisomeric isomer forms.

  该披露涉及新型脂质化合物，制造含有脂质纳米颗粒（LNPs）的方法，含有脂质纳米颗粒（LNPs），以及将LNPs用于传递核酸。所述的脂质化合物是一种可切割的脂质化合物，包括至少一个式（I）的末端基团：Y-(CHR)n-Z-(CHR')p-Q *（I）其中：- *是末端连接的，直接或间接连接到一个C10至C55的亲脂性或疏水性尾基团；- Y是在甲基，甲氧基，三氟甲基，咪唑基中选择的基团，或是一个氢原子；- Z是一个基团-NH-CH2-CO-O-**或一个基团-CR''(NH2)-CO-O-**，其中**是最接近Q的末端，R''在氢原子，甲基基团和三氟甲基基团中选择；- Q是一个基团-NH-CH2-CO-O-***或一个基团-CR''(NH2)-CO-O-***，其中R''在氢原子，甲基基团和三氟甲基基团中选择，***是直接或间接连接到所述亲脂性或疏水性尾基团的末端；- R和R'是彼此独立的氢原子，甲基基团或三氟甲基基团；- n和p是彼此独立的0、1或2；或其药用可接受的盐，所述化合物以所有可能的外消旋、对映异构体和顄对映异构体形式存在。
• [EN] OLIGOMER CONJUGATES OF LIDOCAINE AND ITS DERIVATIVES<br/>[FR] CONJUGUÉS D'OLIGOMÈRE DE LIDOCAÏNE ET LEURS DÉRIVÉS
  申请人：NEKTAR THERAPEUTICS AL CORP

  公开号：WO2009054916A3

  公开（公告）日：2009-06-04
• Fluorescent Pirenzepine Derivatives as Potential Bitopic Ligands of the Human M1 Muscarinic Receptor
  作者：Chouaib Tahtaoui、Isabelle Parrot、Philippe Klotz、Fabrice Guillier、Jean-Luc Galzi、Marcel Hibert、Brigitte Ilien

  DOI：10.1021/jm040800a

  日期：2004.8.1

  Following a recent description of fluorescence resonance energy transfer between enhanced green fluorescent protein (EGFP)-fused human muscarinic M1 receptors and Bodipy-labeled pirenzepine, we synthesized seven fluorescent derivatives of this antagonist in order to further characterize ligand-receptor interactions. These compounds carry Bodipy [558/568], Rhodamine Red-X [560/580], or Fluorolink Cy3 [550/570] fluorophores connected to pirenzepine through various linkers. All molecules reversibly bind with high affinity to M1 receptors (radioligand and energy transfer binding experiments) provided that the linker contains more than six atoms. The energy transfer efficiency exhibits modest variations among ligands, indicating that the distance separating EGFP from the fluorophores remains almost constant. This also supports the notion that the fluorophores may bind to the receptor protein. Kinetic analyses reveal that the dissociation of two Bodipy derivatives (10 or 12 atom long linkers) is sensitive to the presence of the allosteric modulator brucine, while that of all other molecules (15-24 atom long linkers) is not. The data favor the idea that these analogues might interact with both the acetylcholine and the brucine binding domains.
• Ligand–Phospholipid Conjugation: A Versatile Strategy for Developing Long-Acting Ligands That Bind to Membrane Proteins by Restricting the Subcellular Localization of the Ligand
  作者：Shuhei Kawamura、Yoshihiko Ito、Takatsugu Hirokawa、Eriko Hikiyama、Shizuo Yamada、Satoshi Shuto

  DOI：10.1021/acs.jmedchem.8b00041

  日期：2018.5.10

  We hypothesized that if drug localization can be restricted to a particular subcellular domain where their target proteins reside, the drugs could bind to their target proteins without being metabolized and/or excreted, which would significantly extend the half-life of the corresponding drug target complex. Thus, we designed ligand phospholipid conjugates in which the ligand is conjugated with a phospholipid through a polyethylene glycol linker to restrict the subcellular localization of the ligand in the vicinity of the lipid bilayer. Here, we present the design, synthesis, pharmacological activity, and binding mode analysis of ligand phospholipid conjugates with muscarinic acetylcholine receptors as the target proteins. These results demonstrate that ligand phospholipid conjugation can be a versatile strategy for developing long-acting ligands that bind to membrane proteins in drug discovery.