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 | 322761-78-4

• 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
• 英文名称: 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
• 英文别名: [(2R,3S,4S,5R,6R)-3,5-dibenzoyloxy-4-[(2S)-3-cyclohexyl-1-oxo-1-phenylmethoxypropan-2-yl]oxy-6-[(2R,3S,4R)-2-(hydroxymethyl)-3-[(2S,3S,4R,5R,6S)-6-methyl-3,4,5-tris(phenylmethoxy)oxan-2-yl]oxyoxan-4-yl]oxyoxan-2-yl]methyl benzoate
• CAS: 322761-78-4
• 化学式: C₇₆H₈₂O₁₈
• 分子量: 1283.48
• InChiKey: PTJSAEWYZNTKPH-WDWXDASASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.54
• 重原子数：
  94.0
• 可旋转键数：
  28.0
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  208.5
• 氢给体数：
  1.0
• 氢受体数：
  18.0

反应信息

• 作为反应物：
  描述：

  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 在 palladium on activated charcoal 氢气 、 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 Sodium; (S)-2-{(2R,3R,4S,5S,6R)-3-benzoyloxy-5-hydroxy-6-hydroxymethyl-2-[(2R,3S,4R)-2-hydroxymethyl-3-((2S,3S,4R,5S,6S)-3,4,5-trihydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-4-yloxy]-tetrahydro-pyran-4-yloxy}-3-cyclohexyl-propionate
  参考文献：
  名称：

  A Readily Available, Highly Potent E-Selectin Antagonist

  摘要：

  DOI：

  10.1002/1521-3773(20011001)40:19<3644::aid-anie3644>3.0.co;2-s
• 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 咪唑 、 N-碘代丁二酰亚胺 、 molecular sieve 、 三氟甲磺酸 、 四乙基溴化铵 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 、 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

文献信息

• [EN] GLYCOMIMETIC ANTAGONISTS FOR BOTH E- AND P-SELECTINS<br/>[FR] ANTAGONISTES GLYCOMIMETIQUES POUR LES SELECTINES DE TYPE E ET P
  申请人：GLYCOMIMETICS INC

  公开号：WO2005054264A3

  公开（公告）日：2007-03-22