2-(adenin-9-yl)-1,5-anhydro-6-O-sulfamoyl-4-O-tertbutyldimethylsilyl-2,3-dideoxy-D-arabinohexitol | 1030371-98-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-(adenin-9-yl)-1,5-anhydro-6-O-sulfamoyl-4-O-tertbutyldimethylsilyl-2,3-dideoxy-D-arabinohexitol
• CAS: 1030371-98-2
• 化学式: C₁₇H₃₀N₆O₅SSi
• 分子量: 458.614
• InChiKey: LZIZLOHCGMKSRW-RWMBFGLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.35
• 重原子数：
  30.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  157.47
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  2-(adenin-9-yl)-1,5-anhydro-6-O-sulfamoyl-4-O-tertbutyldimethylsilyl-2,3-dideoxy-D-arabinohexitol 、 叔丁氧羰基-蛋氨酰-琥珀酰亚胺 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66%的产率得到2-(adenin-9-yl)-1,5-anhydro-4-O-tertbutyldimethylsilyl-6-O-[(N-Boc-L-methionyl)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：

  2-(adenin-9-yl)-1,5-anhydro-4-O-tertbutyldimethylsilyl-2,3-dideoxy-D-arabinohexitol 在 氨基磺酰氯 作用下， 以 N,N-二甲基乙酰胺 、 乙腈 为溶剂， 反应 1.0h， 以69%的产率得到2-(adenin-9-yl)-1,5-anhydro-6-O-sulfamoyl-4-O-tertbutyldimethylsilyl-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