| 190587-21-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• CAS: 190587-21-4
• 化学式: C₄₃H₅₁N₃O₉
• 分子量: 753.893
• InChiKey: KCZYWSZIUJPFHN-BMKXFBGNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.59
• 重原子数：
  55.0
• 可旋转键数：
  21.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  156.67
• 氢给体数：
  3.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  在 palladium hydroxide - carbon 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 (S)-4-[(R)-3-[(2R,3S,4S,5R)-3,4-Dihydroxy-5-((S)-1-hydroxy-ethyl)-tetrahydro-furan-2-yloxy]-2-(2-tetradecyl-hexadecanoylamino)-propionylamino]-4-methylcarbamoyl-butyric acid
  参考文献：
  名称：

  Studies on Selectin Blockers. 6. Discovery of Homologous Fucose Sugar Unit Necessary for E-Selectin Binding

  摘要：

  We describe a mimic of the sugar unit of the E-selectin ligand, sialyl Lewis X (sLe(X)). Carbohydrates are entering the realm of rational drug design, aided by the growing understanding of the structure-function relationships. We investigated a new methodology of preparing sLe(X) mimetics and developed a potent E-selectin blocker characterized by beta-turn dipeptides. Another characteristic point of this E-selectin blocker is that the six-membered fucose ring was replaced with a five-membered fucose ring. Interestingly, it was found that the five-membered fucose ring could also bind to a calcium ion on the E-selectin, which could be an important role of the six-membered fucose ring. Especially, the L-Ser-D-Glu and D-Ser-L-Glu derivatives 3a,b showed 65-90-fold more potent inhibitory activities than the sulfated Le(X) analogue 1. In addition, molecular dynamics (MD) studies indicated that the 2- and 3-OH groups of the six-membered fucose ring, which were necessary for the calcium binding, overlapped well with the 2- and 3-OH groups of the five-membered fucose ring. These new findings could be useful for the design of new types of selectin blockers.

  DOI：

  10.1021/jm9707481
• 作为产物：
  描述：

  [N-(tert-butoxycarbonyl)-O-(2,3,5-tri-O-benzyl-α-L-fucofuranosyl)-D-seryl]-L-glutamic acid 1-methylamide 5-benzyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Studies on Selectin Blockers. 6. Discovery of Homologous Fucose Sugar Unit Necessary for E-Selectin Binding

  摘要：

  We describe a mimic of the sugar unit of the E-selectin ligand, sialyl Lewis X (sLe(X)). Carbohydrates are entering the realm of rational drug design, aided by the growing understanding of the structure-function relationships. We investigated a new methodology of preparing sLe(X) mimetics and developed a potent E-selectin blocker characterized by beta-turn dipeptides. Another characteristic point of this E-selectin blocker is that the six-membered fucose ring was replaced with a five-membered fucose ring. Interestingly, it was found that the five-membered fucose ring could also bind to a calcium ion on the E-selectin, which could be an important role of the six-membered fucose ring. Especially, the L-Ser-D-Glu and D-Ser-L-Glu derivatives 3a,b showed 65-90-fold more potent inhibitory activities than the sulfated Le(X) analogue 1. In addition, molecular dynamics (MD) studies indicated that the 2- and 3-OH groups of the six-membered fucose ring, which were necessary for the calcium binding, overlapped well with the 2- and 3-OH groups of the five-membered fucose ring. These new findings could be useful for the design of new types of selectin blockers.

  DOI：

  10.1021/jm9707481