methyl (methyl 5-cyclobutylamido-4,7,8-tri-O-acetyl-9-(4-chlorobenzamido)-3,5,9-trideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosid)onate | 1209013-08-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl (methyl 5-cyclobutylamido-4,7,8-tri-O-acetyl-9-(4-chlorobenzamido)-3,5,9-trideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosid)onate
• CAS: 1209013-08-0
• 化学式: C₂₉H₃₇ClN₂O₁₁S
• 分子量: 657.139
• InChiKey: JLGGNQPUIYFXTL-DUQDEQRNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.17
• 重原子数：
  44.0
• 可旋转键数：
  12.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  172.63
• 氢给体数：
  2.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  methyl (methyl 5-cyclobutylamido-4,7,8-tri-O-acetyl-9-(4-chlorobenzamido)-3,5,9-trideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosid)onate 、 4-氯苯甲醇 在 N-碘代丁二酰亚胺 、 三氟甲磺酸 作用下， 以 乙腈 为溶剂， 反应 1.5h， 以72%的产率得到methyl ((2,3-difluorobenzyl) 5-cyclobutylamido-4,7,8-tri-O-acetyl-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
• 作为产物：
  描述：

  methyl (methyl 5-amino-4,7,8-tri-O-acetyl-9-(4-chlorobenzamido)-3,5,9-trideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosid)onate 、 环丁基甲酰氯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以39%的产率得到methyl (methyl 5-cyclobutylamido-4,7,8-tri-O-acetyl-9-(4-chlorobenzamido)-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