2,3-bis(naphthalen-1-yloxy)propan-1-yl α-D-mannopyranoside | 1581270-79-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,3-bis(naphthalen-1-yloxy)propan-1-yl α-D-mannopyranoside
• 英文别名: (2S,3S,4S,5S,6R)-2-(2,3-dinaphthalen-1-yloxypropoxy)-6-(hydroxymethyl)oxane-3,4,5-triol
• CAS: 1581270-79-2
• 化学式: C₂₉H₃₀O₈
• 分子量: 506.552
• InChiKey: QXEPZQBRJBEFBB-KXOLAGCXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  118
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,3,4,6-四-O-乙酰基吡喃己糖 在 三氟甲磺酸三甲基硅酯 、 sodium methylate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 148.0h， 生成 2,3-bis(naphthalen-1-yloxy)propan-1-yl α-D-mannopyranoside
  参考文献：
  名称：

  Monovalent mannose-based DC-SIGN antagonists: Targeting the hydrophobic groove of the receptor

  摘要：

  Dendritic cell-specific, intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a C-type lectin expressed specifically on dendritic cells. It is a primary site for recognition and binding of various pathogens and thus a promising therapeutic target for inhibition of pathogen entry and subsequent prevention of immune defense cell infection. We report the design and synthesis of D-mannose-based DC-SIGN antagonists bearing diaryl substituted 1,3-diaminopropanol or glycerol moieties incorporated to target the hydrophobic groove of the receptor. The designed glycomimetics were evaluated by in vitro assay of the isolated DC-SIGN extracellular domain for their ability to compete with HIV-1 gp120 for binding to the DC-SIGN carbohydrate recognition domain. Compounds 14d and 14e, that display IC50 values of 40 mu M and 50 mu M, are among the most potent monovalent DC-SIGN antagonists reported. The antagonistic effect of all the synthesized compounds was further evaluated by a one-point in vitro assay that measures DC adhesion. Compounds 14d, 14e, 18d and 18e were shown to act as functional antagonists of DC-SIGN-mediated DC adhesion. The binding mode of 14d was also studied by molecular docking and molecular dynamics simulation, which revealed flexibility of 14d in the binding site and provides a basis for further optimization. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.01.047

文献信息

• Monovalent mannose-based DC-SIGN antagonists: Targeting the hydrophobic groove of the receptor
  作者：Tihomir Tomašić、David Hajšek、Urban Švajger、Jernej Luzar、Nataša Obermajer、Isabelle Petit-Haertlein、Franck Fieschi、Marko Anderluh

  DOI：10.1016/j.ejmech.2014.01.047

  日期：2014.3

  Dendritic cell-specific, intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a C-type lectin expressed specifically on dendritic cells. It is a primary site for recognition and binding of various pathogens and thus a promising therapeutic target for inhibition of pathogen entry and subsequent prevention of immune defense cell infection. We report the design and synthesis of D-mannose-based DC-SIGN antagonists bearing diaryl substituted 1,3-diaminopropanol or glycerol moieties incorporated to target the hydrophobic groove of the receptor. The designed glycomimetics were evaluated by in vitro assay of the isolated DC-SIGN extracellular domain for their ability to compete with HIV-1 gp120 for binding to the DC-SIGN carbohydrate recognition domain. Compounds 14d and 14e, that display IC50 values of 40 mu M and 50 mu M, are among the most potent monovalent DC-SIGN antagonists reported. The antagonistic effect of all the synthesized compounds was further evaluated by a one-point in vitro assay that measures DC adhesion. Compounds 14d, 14e, 18d and 18e were shown to act as functional antagonists of DC-SIGN-mediated DC adhesion. The binding mode of 14d was also studied by molecular docking and molecular dynamics simulation, which revealed flexibility of 14d in the binding site and provides a basis for further optimization. (C) 2014 Elsevier Masson SAS. All rights reserved.