2-(adenin-9-yl)-1,5-anhydro-6-O-[(L-arginyl)sulfamoyl]-2,3-dideoxy-D-arabinohexitol | 1030372-56-5

• 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-[(L-arginyl)sulfamoyl]-2,3-dideoxy-D-arabinohexitol
• 英文别名: [(2R,3S,5S)-5-(6-aminopurin-9-yl)-3-hydroxyoxan-2-yl]methyl N-[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]sulfamate
• CAS: 1030372-56-5
• 化学式: C₁₇H₂₈N₁₀O₆S
• 分子量: 500.539
• InChiKey: UEKKCMBFIDJSLN-FIQHERPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.7
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  270
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2-(adenin-9-yl)-1,5-anhydro-6-O-sulfamoyl-4-O-tertbutyldimethylsilyl-2,3-dideoxy-D-arabinohexitol 、 Boc-Arg(Boc)2OH 在 N-羟基丁二酰亚胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三氟乙酸 作用下， 以 水 为溶剂， 反应 8.0h， 以91%的产率得到2-(adenin-9-yl)-1,5-anhydro-6-O-[(L-arginyl)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

文献信息

• Aminoacyl-tRNA Synthetase Inhibitors as Potent and Synergistic Immunosuppressants
  作者：Pieter Van de Vijver、Tomasz Ostrowski、Brian Sproat、Jozef Goebels、Omer Rutgeerts、Arthur Van Aerschot、Mark Waer、Piet Herdewijn

  DOI：10.1021/jm8000746

  日期：2008.5.1

  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.