1,5-anhydro-2-deoxy-3-O-{2,4,6-tri-O-benzoyl-3-O-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-(phenylmethoxy)ethyl]-β-D-galactopyranosyl}-D-arabino-hexitol | 322761-82-0

• 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
• 英文名称: 1,5-anhydro-2-deoxy-3-O-{2,4,6-tri-O-benzoyl-3-O-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-(phenylmethoxy)ethyl]-β-D-galactopyranosyl}-D-arabino-hexitol
• 英文别名: 1,5-anhydro-2-deoxy-3-O-[2,4,6-tri-O-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-(phenylmethoxy)ethyl]-β-D-galactopyranosyl]-D-arabino-hexitol；[(2R,3S,4S,5R,6R)-3,5-dibenzoyloxy-4-[(2S)-3-cyclohexyl-1-oxo-1-phenylmethoxypropan-2-yl]oxy-6-[(2R,3S,4R)-3-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxyoxan-2-yl]methyl benzoate
• CAS: 322761-82-0
• 化学式: C₄₉H₅₄O₁₄
• 分子量: 866.959
• InChiKey: SDXWGGKXUZMFLH-SRADQQQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.01
• 重原子数：
  63.0
• 可旋转键数：
  17.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  182.58
• 氢给体数：
  2.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  1,5-anhydro-2-deoxy-3-O-{2,4,6-tri-O-benzoyl-3-O-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-(phenylmethoxy)ethyl]-β-D-galactopyranosyl}-D-arabino-hexitol 在 咪唑 、 molecular sieve 、 四乙基溴化铵 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 68.0h， 生成 O-3-O-[(1S)-1-cyclohexylmethyl)-2-oxo-2-(phenylmethoxy)ethyl]-2,4,6-tris-O-(phenylmethyl)-β-D-galactopyranosyl-(1->3)-O-[6-deoxy-2,3,4-tris-O-(phenylmethyl)-α-L-galactopyranosyl-(1->4)]-1,5-anhydro-2-deoxy-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
• 作为产物：
  描述：

  ethyl 3-O-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-(phenylmethoxy)ethyl]-1-thio-β-D-galactopyranoside 2,4,6-tribenzoate 在 N-碘代丁二酰亚胺 、 三氟甲磺酸 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 1,5-anhydro-2-deoxy-3-O-{2,4,6-tri-O-benzoyl-3-O-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-(phenylmethoxy)ethyl]-β-D-galactopyranosyl}-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

• Simplified Sialyl Lewisx Analogues with Improved E-Selectin Inhibition
  作者：Gebhard Thoma、Franz Schwarzenbach

  DOI：10.1002/hlca.200390085

  日期：2003.3

  simplified sialyl Lewisx mimic 5 containing a D-arabinose, a 3-cyclohexyl-2-hydroxypropanoate, and a tetrahydropyran building block instead of L-fucose, sialic acid, and N-acetylglucosamine, respectively was synthesized. Compound 5 was 10-fold more potent than sLex in a static E-selectin binding assay and showed at 50 μM 75% inhibition in a dynamic-flow assay in which sLex did not inhibit neutrophil

  合成了分别包含D-阿拉伯糖，3-环己基-2-羟基丙酸酯和四氢吡喃结构单元而不是L-岩藻糖，唾液酸和N-乙酰基葡糖胺的简化的唾液酸化的Lewis x mimic 5。在静态E-选择素结合测定中，化合物5的效力比sLe x高10倍，在动态流量测定中，sLe x在最高1000μM时不抑制嗜中性粒细胞滚动，在动态流量测定中显示50％抑制75％。与sLe x相比，具有乳酸而不是唾液酸结构单元的化合物7的效能提高了三倍。