2-(adenin-9-yl)-1,5-anhydro-4-O-tertbutyldimethylsilyl-6-O-[(N-Boc-L-leucyl)sulfamoyl]-2,3-dideoxy-D-arabinohexitol | 1030372-47-4

• 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: 2-(adenin-9-yl)-1,5-anhydro-4-O-tertbutyldimethylsilyl-6-O-[(N-Boc-L-leucyl)sulfamoyl]-2,3-dideoxy-D-arabinohexitol
• CAS: 1030372-47-4
• 化学式: C₂₈H₄₉N₇O₈SSi
• 分子量: 671.891
• InChiKey: WLCHMYDTFJYDNU-XSDIEEQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.45
• 重原子数：
  45.0
• 可旋转键数：
  11.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  198.88
• 氢给体数：
  3.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  2-(adenin-9-yl)-1,5-anhydro-4-O-tertbutyldimethylsilyl-6-O-[(N-Boc-L-leucyl)sulfamoyl]-2,3-dideoxy-D-arabinohexitol 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 5.0h， 以77%的产率得到2-(adenin-9-yl)-1,5-anhydro-6-O-[N-(L-leucyl)sulfamoyl]-2,3-dideoxy-D-arabinohexitol
  参考文献：
  名称：

  Aminoacyl-tRNA Synthetase Inhibitors as Potent and Synergistic Immunosuppressants

  摘要：

  The aminoacyl-tRNA synthetase family of enzymes is the target of many antibacterials and inhibitors of eukaryotic hyperproliferation. In screening analogues of 5'-O-(N-L-aminoacyl)-sulfamoyladenosine containing all 20 proteinogenic amino acids, we found these compounds to have potent immunosuppressive activity. Also, we found that combinations of these compounds inhibited the immune response synergistically. Based on these data, analogues with modifications at the aminoacyl and ribose moieties were designed and evaluated, and several of these showed high immunosuppressive potency, with one compound having an IC(50) of 80 nM, when tested in a cellular mixed lymphocyte reaction assay. Apart from showing the potential of aminoacyl-tRNA synthetase inhibitors as immunosuppressants, the current study also provides arguments for careful evaluation of the immunosuppressive activity of developmental antibacterials that target these enzymes.

  DOI：

  10.1021/jm8000746
• 作为产物：
  描述：

  Boc-L-亮氨酸N-羟基琥珀酰亚胺脂 、 2-(adenin-9-yl)-1,5-anhydro-6-O-sulfamoyl-4-O-tertbutyldimethylsilyl-2,3-dideoxy-D-arabinohexitol 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以96%的产率得到2-(adenin-9-yl)-1,5-anhydro-4-O-tertbutyldimethylsilyl-6-O-[(N-Boc-L-leucyl)sulfamoyl]-2,3-dideoxy-D-arabinohexitol
  参考文献：
  名称：

  Aminoacyl-tRNA Synthetase Inhibitors as Potent and Synergistic Immunosuppressants

  摘要：

  The aminoacyl-tRNA synthetase family of enzymes is the target of many antibacterials and inhibitors of eukaryotic hyperproliferation. In screening analogues of 5'-O-(N-L-aminoacyl)-sulfamoyladenosine containing all 20 proteinogenic amino acids, we found these compounds to have potent immunosuppressive activity. Also, we found that combinations of these compounds inhibited the immune response synergistically. Based on these data, analogues with modifications at the aminoacyl and ribose moieties were designed and evaluated, and several of these showed high immunosuppressive potency, with one compound having an IC(50) of 80 nM, when tested in a cellular mixed lymphocyte reaction assay. Apart from showing the potential of aminoacyl-tRNA synthetase inhibitors as immunosuppressants, the current study also provides arguments for careful evaluation of the immunosuppressive activity of developmental antibacterials that target these enzymes.

  DOI：

  10.1021/jm8000746