4-amino-3-bromo-1-(5-amino-5-deoxy-2,3-O-isopropylidene-α-L-lyxofuranosyl)pyrazolo[3,4-d]pyrimidine | 624727-97-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 4-amino-3-bromo-1-(5-amino-5-deoxy-2,3-O-isopropylidene-α-L-lyxofuranosyl)pyrazolo[3,4-d]pyrimidine
• 英文别名: 1-[(3aR,4R,6S,6aR)-6-(aminomethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-3-bromopyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 624727-97-5
• 化学式: C₁₃H₁₇BrN₆O₃
• 分子量: 385.22
• InChiKey: MAZJSIDGGVHERE-VBKWPLKRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-amino-3-bromo-1-(5-amino-5-deoxy-2,3-O-isopropylidene-α-L-lyxofuranosyl)pyrazolo[3,4-d]pyrimidine 在 三氟乙酸 作用下， 以32%的产率得到(2S,3S,4R,5R)-2-(4-Amino-3-bromo-pyrazolo[3,4-d]pyrimidin-1-yl)-5-aminomethyl-tetrahydro-furan-3,4-diol
  参考文献：
  名称：

  Adenosine Kinase Inhibitors. 3. Synthesis, SAR, and Antiinflammatory Activity of a Series of l-Lyxofuranosyl Nucleosides

  摘要：

  Chronic inflammatory diseases, such as arthritis and rheumatoid arthritis, remain major health problems worldwide. We previously demonstrated that adenosine kinase inhibitors (AKIs) exhibit antiinflammatory effects by inhibiting TNF-alpha production, neutrophil accumulation, and edema formation. Although adenosine receptor agonists produce similar effects, AKIs showed the antiinflammatory activity without the cardiovascular side effects that prevented the development of adenosine receptor specific agonists. However, previously described potent AKIs, such as 5-iodotubercidin, are nucleosides which have the potential to undergo in vivo 5'-O-phosphorylation and therefore produce cytotoxicity. In an effort to eliminate toxicities produced by phosphorylated nucleosides, L-lyxofuranosyl analogues of tubercidin were tested as potential AKIs since the opposite stereochemical. orientation of the CH2OH was expected to eliminate intracellular phosphorylation. Described herein are the discovery of a new series of AKIs based on alpha-L-lyxofuranosyl. nucleosides, their SAR, as well as the antiinflammatory activity of the lead compound GP790 (IC50 = 0.47 nM, 47% inhibition of paw swelling at 10 mg/kg in rat carrageenan paw edema model). In addition, a study showing that in the skin lesion model the antiinflammatory activity is reversed by an A2 selective adenosine receptor antagonist 3,7-dimethyl-1-propylxanthine (DMPX) is also described.

  DOI：

  10.1021/jm030230z
• 作为产物：
  描述：

  methyl L-lyxofuranoside 在 盐酸 、 4-二甲氨基吡啶 、 硝基甲烷 、 硫酸 、 三氟化硼乙醚 、 氨 、 sodium methylate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 吡啶 、 甲醇 、 丙酮 为溶剂， 反应 76.0h， 生成 4-amino-3-bromo-1-(5-amino-5-deoxy-2,3-O-isopropylidene-α-L-lyxofuranosyl)pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  Adenosine Kinase Inhibitors. 3. Synthesis, SAR, and Antiinflammatory Activity of a Series of l-Lyxofuranosyl Nucleosides

  摘要：

  Chronic inflammatory diseases, such as arthritis and rheumatoid arthritis, remain major health problems worldwide. We previously demonstrated that adenosine kinase inhibitors (AKIs) exhibit antiinflammatory effects by inhibiting TNF-alpha production, neutrophil accumulation, and edema formation. Although adenosine receptor agonists produce similar effects, AKIs showed the antiinflammatory activity without the cardiovascular side effects that prevented the development of adenosine receptor specific agonists. However, previously described potent AKIs, such as 5-iodotubercidin, are nucleosides which have the potential to undergo in vivo 5'-O-phosphorylation and therefore produce cytotoxicity. In an effort to eliminate toxicities produced by phosphorylated nucleosides, L-lyxofuranosyl analogues of tubercidin were tested as potential AKIs since the opposite stereochemical. orientation of the CH2OH was expected to eliminate intracellular phosphorylation. Described herein are the discovery of a new series of AKIs based on alpha-L-lyxofuranosyl. nucleosides, their SAR, as well as the antiinflammatory activity of the lead compound GP790 (IC50 = 0.47 nM, 47% inhibition of paw swelling at 10 mg/kg in rat carrageenan paw edema model). In addition, a study showing that in the skin lesion model the antiinflammatory activity is reversed by an A2 selective adenosine receptor antagonist 3,7-dimethyl-1-propylxanthine (DMPX) is also described.

  DOI：

  10.1021/jm030230z