O-3-O-[(1S)-1-carboxy-2-cyclohexylethyl]-β-D-galactopyranosyl-(1->3)-O-[6-deoxy-α-L-galactopyranosyl-(1->4)]-1,5-anhydro-2,6-dideoxy-6-[(1-oxo-2,2-diphenylethyl)amino]-D-arabino-hexitol

• 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: O-3-O-[(1S)-1-carboxy-2-cyclohexylethyl]-β-D-galactopyranosyl-(1->3)-O-[6-deoxy-α-L-galactopyranosyl-(1->4)]-1,5-anhydro-2,6-dideoxy-6-[(1-oxo-2,2-diphenylethyl)amino]-D-arabino-hexitol
• 英文别名: (2S)-3-cyclohexyl-2-[(2R,3R,4S,5S,6R)-2-[(2R,3S,4R)-2-[[(2,2-diphenylacetyl)amino]methyl]-3-[(2S,3S,4R,5S,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-4-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxypropanoic acid
• 化学式: C₄₁H₅₇NO₁₅
• 分子量: 803.901
• InChiKey: YSZUZPDJTPZLKG-FERFDWOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  57
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  243
• 氢给体数：
  8
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  O-3-O-{2,4,6-tri-O-benzoyl-3-O-[(1S)-1-cyclohexylmethyl)-2-oxo-2-(phenylmethoxy)ethyl]-β-D-galactopyranosyl-(1->3)-O-[6-deoxy-2,3,4-tris-O-(phenylmethyl)-α-L-galactopyranosyl-(1->4)]}-1,5-anhydro-6-azido-2,6-dideoxy-D-arabino-hexitol 在 palladium on activated charcoal lithium hydroxide 、 sodium hydroxide 、 氢气 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 40.0h， 生成 O-3-O-[(1S)-1-carboxy-2-cyclohexylethyl]-β-D-galactopyranosyl-(1->3)-O-[6-deoxy-α-L-galactopyranosyl-(1->4)]-1,5-anhydro-2,6-dideoxy-6-[(1-oxo-2,2-diphenylethyl)amino]-D-arabino-hexitol
  参考文献：
  名称：

  Potent E-Selectin Antagonists

  摘要：

  In the search for drugs that could control excessive leukocyte extravasation, we now report on modifications of the already known potent E-selectin antagonist 3 containing a cyclohexyllactic acid residue and a glucal-derived building block. Thus, we describe the synthesis and biological evaluation of a series of derivatives 6 with modified glucal-derived moieties ((CH2NRR2)-R-1 instead of CH2OH in 3) to explore a hypothetical potential complementary interaction with E-selectin. However, similar activity profiles of most derivatives 6 and compound 3 do not support such an interaction, but rather indicate topological-structure changes of 6 (and 3) in the orientation of the neighboring fucose and galactose due to intramolecular steric interactions. The most potent E-selectin antagonist 6v showed >50-fold improved E-selectin inhibition compared to the weak selectin ligand sialyl Lewis(x) (sLe(x), 1; IC50 = 1000-1500 muM), but only a 2-fold improvement compared to 3. Compound 6x was tested in vivo in a murine model of acute inflammation and found to be as potent as 3 (ED50 = 15 mg/kg).

  DOI：

  10.1002/1522-2675(20001108)83:11<2893::aid-hlca2893>3.0.co;2-g

文献信息

• Potent E-Selectin Antagonists
  作者：Rolf Bänteli、Peter Herold、Christian Bruns、John T. Patton、John L. Magnani、Gebhard Thoma

  DOI：10.1002/1522-2675(20001108)83:11<2893::aid-hlca2893>3.0.co;2-g

  日期：2000.11.8

  In the search for drugs that could control excessive leukocyte extravasation, we now report on modifications of the already known potent E-selectin antagonist 3 containing a cyclohexyllactic acid residue and a glucal-derived building block. Thus, we describe the synthesis and biological evaluation of a series of derivatives 6 with modified glucal-derived moieties ((CH2NRR2)-R-1 instead of CH2OH in 3) to explore a hypothetical potential complementary interaction with E-selectin. However, similar activity profiles of most derivatives 6 and compound 3 do not support such an interaction, but rather indicate topological-structure changes of 6 (and 3) in the orientation of the neighboring fucose and galactose due to intramolecular steric interactions. The most potent E-selectin antagonist 6v showed >50-fold improved E-selectin inhibition compared to the weak selectin ligand sialyl Lewis(x) (sLe(x), 1; IC50 = 1000-1500 muM), but only a 2-fold improvement compared to 3. Compound 6x was tested in vivo in a murine model of acute inflammation and found to be as potent as 3 (ED50 = 15 mg/kg).