methyl (methyl 5-acetamido-9-azido-3,5,9-trideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosid)onate | 1209012-66-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl (methyl 5-acetamido-9-azido-3,5,9-trideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosid)onate
• 英文别名: methyl (methyl 5-acetamido-9-azido-2-thio-3,5,9-trideoxy-D-glycero-D-galacto-2-nonulopyranosid)onate
• CAS: 1209012-66-7
• 化学式: C₁₃H₂₂N₄O₇S
• 分子量: 378.406
• InChiKey: MJIABUFGOLLHEZ-GRRZBWEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.09
• 重原子数：
  25.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  174.08
• 氢给体数：
  4.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  methyl (methyl 5-acetamido-9-azido-3,5,9-trideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosid)onate 、 乙酸酐 在 吡啶 、 4-二甲氨基吡啶 作用下， 以73%的产率得到methyl (methyl 5-acetamido-4,7,8-tri-O-acetyl-9-azido-3,5,9-trideoxy-2-thio-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
• 作为产物：
  描述：

  methyl (methyl 5-acetamido-3,5-dideoxy-2-thio-9-tosyl-D-glycero-α-D-galacto-2-nonulopyranosid)onate 在 sodium azide 、 15-冠醚-5 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以78%的产率得到methyl (methyl 5-acetamido-9-azido-3,5,9-trideoxy-2-thio-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

• A Fragment-Based In Situ Combinatorial Approach To Identify High-Affinity Ligands for Unknown Binding Sites
  作者：Sachin V. Shelke、Brian Cutting、Xiaohua Jiang、Hendrik Koliwer-Brandl、Daniel S. Strasser、Oliver Schwardt、Soerge Kelm、Beat Ernst

  DOI：10.1002/anie.200907254

  日期：——

  the lead: The title method for the identification of ligands is particularly useful for binding sites where little or no structural information is available. In a fragment‐based approach, a suitable pair of first‐ and second‐site ligands is identified by NMR experiments. By applying a receptor‐mediated in situ combinatorial approach, the two ligands are then linked to generate a new high‐affinity lead

  潜在客户：鉴定配体的标题方法特别适用于很少或没有结构信息的结合位点。在基于片段的方法中，通过NMR实验确定了合适的一对第一位和第二位配体。通过应用受体介导的原位组合方法，然后将两个配体连接起来以生成新的高亲和力铅结构（参见图片）。