sodium ((2,3-difluorobenzyl) 5-fluoroacetamido-9-(4-chlorobenzamido)-3,5,9-trideoxy-D-glycero-α-D-galacto-2-nonulopyranosid)onate | 1209012-64-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: sodium ((2,3-difluorobenzyl) 5-fluoroacetamido-9-(4-chlorobenzamido)-3,5,9-trideoxy-D-glycero-α-D-galacto-2-nonulopyranosid)onate
• 英文别名: sodium;N-[(2R,3R,4S,6R)-6-carboxy-2-[(1R,2R)-3-[(4-chlorobenzoyl)amino]-1,2-dihydroxypropyl]-6-[(2,3-difluorophenyl)methoxy]-4-hydroxyoxan-3-yl]-2-fluoroethanimidate
• CAS: 1209012-64-5
• 化学式: C₂₅H₂₅ClF₃N₂O₉*Na
• 分子量: 612.919
• InChiKey: GKUUIJYNUIUVCX-QWNWARSQSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -3.66
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  181
• 氢给体数：
  5
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  (2R,4S,5R,6R)-6-[(1R,2R)-3-[(4-chlorobenzoyl)amino]-1,2-dihydroxypropyl]-2-[(2,3-difluorophenyl)methoxy]-5-[(2-fluoroacetyl)amino]-4-hydroxyoxane-2-carboxylic acid 在 Dowex 50, Na⁺ form 作用下， 以7 mg的产率得到sodium ((2,3-difluorobenzyl) 5-fluoroacetamido-9-(4-chlorobenzamido)-3,5,9-trideoxy-D-glycero-α-D-galacto-2-nonulopyranosid)onate
  参考文献：
  名称：

  Low Molecular Weight Antagonists of the Myelin-Associated Glycoprotein: Synthesis, Docking, and Biological Evaluation

  摘要：

  The Injured adult mammalian central nervous system Is all inhibitory environment for axon regeneration due to specific inhibitors,among them the myelin-associated glycoprotein (MAG), a member of the Siglec family (sialic-acid binding immunoglobulin-like lectin). In earlier Studies, we identified the lead structure5, which shows a 250-fold improved in vitro affinity for MAG compared to the tetrasaccharide binding epitope of GQ1b alpha (1), the best physiological MAG ligand described so far. By modifying the 2- and 5-position, the affinity of 5 could be further improved to the nanomolar range (-> 19a). Docking Studies to a homology model of MAG allowed the rationalization of the experimental binding properties. Finally, pharmacokinetic parameters (stability in the cerebrospinal fluid, logD and Permeation through the BBB) indicate the drug-like properties of the high-affinity antagonist 19a.

  DOI：

  10.1021/jm901517k

文献信息

• Low Molecular Weight Antagonists of the Myelin-Associated Glycoprotein: Synthesis, Docking, and Biological Evaluation
  作者：Stefanie Mesch、Delia Moser、Daniel S. Strasser、Antje Kelm、Brian Cutting、Gianluca Rossato、Angelo Vedani、Hendrik Koliwer-Brandl、Matthias Wittwer、Said Rabbani、Oliver Schwardt、Soerge Kelm、Beat Ernst

  DOI：10.1021/jm901517k

  日期：2010.2.25

  The Injured adult mammalian central nervous system Is all inhibitory environment for axon regeneration due to specific inhibitors,among them the myelin-associated glycoprotein (MAG), a member of the Siglec family (sialic-acid binding immunoglobulin-like lectin). In earlier Studies, we identified the lead structure5, which shows a 250-fold improved in vitro affinity for MAG compared to the tetrasaccharide binding epitope of GQ1b alpha (1), the best physiological MAG ligand described so far. By modifying the 2- and 5-position, the affinity of 5 could be further improved to the nanomolar range (-> 19a). Docking Studies to a homology model of MAG allowed the rationalization of the experimental binding properties. Finally, pharmacokinetic parameters (stability in the cerebrospinal fluid, logD and Permeation through the BBB) indicate the drug-like properties of the high-affinity antagonist 19a.