(1R,3R,4R,5S)-3-[2-O-benzoyl-3-O-((1S)-1-carboxy-2-cyclohexylethyl)-(β-Dgalactopyranosyl)oxy]-4-[(α-L-fucopyranosyl)oxy]-5-methyl-N-(2-{1-[4-(5-nitro-1H-indol-1-yl)butyl]-1H-1,2,3-triazol-4-yl}ethyl)cyclohexanecarboxamide | 1365478-72-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 糖脂
• 英文名称: (1R,3R,4R,5S)-3-[2-O-benzoyl-3-O-((1S)-1-carboxy-2-cyclohexylethyl)-(β-Dgalactopyranosyl)oxy]-4-[(α-L-fucopyranosyl)oxy]-5-methyl-N-(2-{1-[4-(5-nitro-1H-indol-1-yl)butyl]-1H-1,2,3-triazol-4-yl}ethyl)cyclohexanecarboxamide
• 英文别名: (2S)-2-[(2R,3S,4S,5R,6R)-5-benzoyloxy-3-hydroxy-2-(hydroxymethyl)-6-[(1R,2R,3S,5R)-3-methyl-5-[2-[1-[4-(5-nitroindol-1-yl)butyl]triazol-4-yl]ethylcarbamoyl]-2-[(2S,3S,4R,5S,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxycyclohexyl]oxyoxan-4-yl]oxy-3-cyclohexylpropanoic acid
• CAS: 1365478-72-3
• 化学式: C₅₂H₇₀N₆O₁₇
• 分子量: 1051.16
• InChiKey: XLCQIRNUDQYDQJ-HHAUDNNZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  75
• 可旋转键数：
  22
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  322
• 氢给体数：
  7
• 氢受体数：
  19

反应信息

• 作为产物：
  描述：

  {(1R,3R,4R,5S)-4-[(α-L-fucopyranosyl)oxy]-1-methoxycarbonyl-5-methylcyclohex-3-yl} 2-O-benzoyl-3-O-[(1S)-1-carboxy-2-cyclohexylethyl]-β-D-galactopyranoside 在 copper(ll) sulfate pentahydrate 、 四丁基氟化铵 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 sodium ascorbate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 4.58h， 生成 (1R,3R,4R,5S)-3-[2-O-benzoyl-3-O-((1S)-1-carboxy-2-cyclohexylethyl)-(β-Dgalactopyranosyl)oxy]-4-[(α-L-fucopyranosyl)oxy]-5-methyl-N-(2-{1-[4-(5-nitro-1H-indol-1-yl)butyl]-1H-1,2,3-triazol-4-yl}ethyl)cyclohexanecarboxamide
  参考文献：
  名称：

  Nanomolar E-Selectin Antagonists with Prolonged Half-Lives by a Fragment-Based Approach

  摘要：

  Selectins, a family of C-type lectins, play a key role in inflammatory diseases (e.g., asthma and arthritis). However, the only millimolar affinity of sialyl Lewis(x) (sLe(x)), which is the common tetrasaccharide epitope of all physiological selectin ligands, has been a major obstacle to the development of selectin antagonists for therapeutic applications. In a fragment-based approach guided by NMR, ligands binding to a second site in close proximity to a sLe(x) mimic were identified. A library of antagonists obtained by connecting the sLe(x) mimic to the best second-site ligand via triazole linkers of different lengths was evaluated by surface plasmon resonance. Detailed analysis of the five most promising candidates revealed antagonists with K-D values ranging from 30 to 89 nM. In contrast to carbohydratelectin complexes with typical half-lives (t(1/2)) in the range of one second or even less, these fragment-based selectin antagonists show t(1/2) of several minutes. They exhibit a promising starting point for the development of novel anti-inflammatory drugs.

  DOI：

  10.1021/ja4029582

文献信息

• Nanomolar E-Selectin Antagonists with Prolonged Half-Lives by a Fragment-Based Approach
  作者：Jonas Egger、Céline Weckerle、Brian Cutting、Oliver Schwardt、Said Rabbani、Katrin Lemme、Beat Ernst

  DOI：10.1021/ja4029582

  日期：2013.7.3

  Selectins, a family of C-type lectins, play a key role in inflammatory diseases (e.g., asthma and arthritis). However, the only millimolar affinity of sialyl Lewis(x) (sLe(x)), which is the common tetrasaccharide epitope of all physiological selectin ligands, has been a major obstacle to the development of selectin antagonists for therapeutic applications. In a fragment-based approach guided by NMR, ligands binding to a second site in close proximity to a sLe(x) mimic were identified. A library of antagonists obtained by connecting the sLe(x) mimic to the best second-site ligand via triazole linkers of different lengths was evaluated by surface plasmon resonance. Detailed analysis of the five most promising candidates revealed antagonists with K-D values ranging from 30 to 89 nM. In contrast to carbohydratelectin complexes with typical half-lives (t(1/2)) in the range of one second or even less, these fragment-based selectin antagonists show t(1/2) of several minutes. They exhibit a promising starting point for the development of novel anti-inflammatory drugs.