diethyl 3,3'-((2-((3-ethoxy-3-oxopropoxy)methyl)-2-(pentacosa-10,12-diynamido)propane-1,3-diyl)bis(oxy))dipropionate | 1435941-40-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: diethyl 3,3'-((2-((3-ethoxy-3-oxopropoxy)methyl)-2-(pentacosa-10,12-diynamido)propane-1,3-diyl)bis(oxy))dipropionate
• CAS: 1435941-40-4
• 化学式: C₄₄H₇₅NO₁₀
• 分子量: 778.08
• InChiKey: MKYPANITFIVZAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.19
• 重原子数：
  55.0
• 可旋转键数：
  37.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  135.69
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  diethyl 3,3'-((2-((3-ethoxy-3-oxopropoxy)methyl)-2-(pentacosa-10,12-diynamido)propane-1,3-diyl)bis(oxy))dipropionate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 14.0h， 以94%的产率得到3,3'-((2-((2-carboxyethoxy)methyl)-2-(pentacosa-10,12-diynamido)propane-1,3-diyl)bis(oxy))dipropionic acid
  参考文献：
  名称：

  [EN] MANNOSYLATED COMPOUNDS USEFUL FOR THE PREVENTION AND THE TREATMENT OF INFECTIOUS DISEASES
  [FR] COMPOSÉS MANNOSYLÉS UTILISÉS DANS LA PRÉVENTION ET LE TRAITEMENT DE MALADIES INFECTIEUSES

  摘要：

  本发明涉及由(i) 一个具有一个到三个甘露糖、二甘露糖或三甘露糖基团的极性头部，通过适当的连接剂连接到(ii) 至少含有17个碳原子长度的单一脂肪链的新型抗感染化合物。同时提供了药物组合物和治疗用途。

  公开号：

  WO2013072355A1
• 作为产物：
  描述：

  10,12-二十五碳二炔酸 、 3-[2-Amino-3-(2-ethoxycarbonyl-ethoxy)-2-(2-ethoxycarbonyl-ethoxymethyl)-propoxy]-propionic acid ethyl ester 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 16.0h， 以57%的产率得到diethyl 3,3'-((2-((3-ethoxy-3-oxopropoxy)methyl)-2-(pentacosa-10,12-diynamido)propane-1,3-diyl)bis(oxy))dipropionate
  参考文献：
  名称：

  [EN] MANNOSYLATED COMPOUNDS USEFUL FOR THE PREVENTION AND THE TREATMENT OF INFECTIOUS DISEASES
  [FR] COMPOSÉS MANNOSYLÉS UTILISÉS DANS LA PRÉVENTION ET LE TRAITEMENT DE MALADIES INFECTIEUSES

  摘要：

  本发明涉及由(i) 一个具有一个到三个甘露糖、二甘露糖或三甘露糖基团的极性头部，通过适当的连接剂连接到(ii) 至少含有17个碳原子长度的单一脂肪链的新型抗感染化合物。同时提供了药物组合物和治疗用途。

  公开号：

  WO2013072355A1

文献信息

• Dynamic Micelles of Mannoside Glycolipids are more Efficient than Polymers for Inhibiting HIV-1 <i>trans</i>-Infection
  作者：Evelyne Schaeffer、Laure Dehuyser、David Sigwalt、Vincent Flacher、Serena Bernacchi、Olivier Chaloin、Jean-Serge Remy、Christopher G. Mueller、Rachid Baati、Alain Wagner

  DOI：10.1021/bc4000806

  日期：2013.11.20

  Mannoside glycolipid conjugates are able to inhibit human immunodeficiency virus type 1 (HIV-1) trans-infection mediated by human dendritic cells (DCs). The conjugates are formed by three building blocks: a linear or branched mannose head, a hydrophilic linker, and a 24-carbon lipid chain. We have shown that, even as single molecules, these compounds efficiently target mannose-binding lectins, such as DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) important for HIV-1 transmission. With the goal to optimize their inhibitory activity by supramolecular structure formation, we have compared saturated and unsaturated conjugates, as single molecules, self-assemblies of dynamic micelles, and photopolymerized cross-linked polymers. Surface plasmon resonance showed that, unexpectedly, polymers of trivalent conjugates did not display a higher binding affinity for DC-SIGN than single molecules. Interactions on a chip or in solution were independent of calcium; however, binding to DCs was inhibited by a calcium chelator. Moreover, HIV-1 trans-infection was mostly inhibited by dynamic micelles and not by rigid polymers. The inhibition data revealed a clear correlation between the structure and molecular assembly of a conjugate and its biological antiviral activity. We present an interaction model between DC-SIGN and conjugates-either single molecules, micelles, or polymers-that highlights that the most effective interactions by dynamic micelles involve both mannose heads and lipid chains. Our data reveal that trivalent glycolipid conjugates display the highest microbicide potential for HIV prophylaxis, as dynamic micelles conjugates and not as rigid polymers.