9-[(3aR,4R,6R,6aR)-6-(dichlorophosphanyloxymethyl)-2-methoxy-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2-chloropurin-6-amine | 1442659-69-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 9-[(3aR,4R,6R,6aR)-6-(dichlorophosphanyloxymethyl)-2-methoxy-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2-chloropurin-6-amine
• CAS: 1442659-69-9
• 化学式: C₁₂H₁₃Cl₃N₅O₅P
• 分子量: 444.598
• InChiKey: MSFVLUKACUOXIQ-BFINSNOLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  9-[(3aR,4R,6R,6aR)-6-(dichlorophosphanyloxymethyl)-2-methoxy-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2-chloropurin-6-amine 在 三正丁胺 、 dimethyl sulfide borane 、 三乙基碳酸氢铵缓冲液 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  Highly Efficient Biocompatible Neuroprotectants with Dual Activity as Antioxidants and P2Y Receptor Agonists

  摘要：

  Currently, there is a need for novel, biocompatible, and effective neuroprotectants for the treatment of neurodegenerative diseases and brain injury associated with oxidative damage. Here, we developed nucleotide-based neuroprotectants acting dually as antioxidants and P2Y-R agonists. To improve the potency, selectivity, and metabolic stability of ATP/ADP, we substituted adenine C2-position by Cl and P-alpha/P-beta position by borano group, 6-9. Nucleotides 6-9 inhibited oxidation in cell-free systems (Fe(II)-H2O2), as detected by ESR (IC50 up to 175 mu M), and ABTS assay (IC50 up to 40 mu M). They also inhibited FeSO4-induced oxidative stress in PC12 cells (IC50 of 80-200 nM). 2-Cl-ADP(alpha-BH3), 7a, was found to be the most potent P2Y(1)-R agonist currently known (EC50 7 nM) and protected primary cortical neurons from FeSO4 insult (EC50 170 nM). In addition, it proved to be metabolically stable in human blood serum (t(1/2) 7 vs 1.5 h for ADP). Hence, we propose 7a as a highly promising neuroprotectant.

  DOI：

  10.1021/jm400197m
• 作为产物：
  描述：

  2-氯腺嘌呤核苷 在 磷酸三甲酯 、 1,8-双二甲氨基萘 、 对甲苯磺酸 作用下， 反应 3.83h， 生成 9-[(3aR,4R,6R,6aR)-6-(dichlorophosphanyloxymethyl)-2-methoxy-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2-chloropurin-6-amine
  参考文献：
  名称：

  Highly Efficient Biocompatible Neuroprotectants with Dual Activity as Antioxidants and P2Y Receptor Agonists

  摘要：

  Currently, there is a need for novel, biocompatible, and effective neuroprotectants for the treatment of neurodegenerative diseases and brain injury associated with oxidative damage. Here, we developed nucleotide-based neuroprotectants acting dually as antioxidants and P2Y-R agonists. To improve the potency, selectivity, and metabolic stability of ATP/ADP, we substituted adenine C2-position by Cl and P-alpha/P-beta position by borano group, 6-9. Nucleotides 6-9 inhibited oxidation in cell-free systems (Fe(II)-H2O2), as detected by ESR (IC50 up to 175 mu M), and ABTS assay (IC50 up to 40 mu M). They also inhibited FeSO4-induced oxidative stress in PC12 cells (IC50 of 80-200 nM). 2-Cl-ADP(alpha-BH3), 7a, was found to be the most potent P2Y(1)-R agonist currently known (EC50 7 nM) and protected primary cortical neurons from FeSO4 insult (EC50 170 nM). In addition, it proved to be metabolically stable in human blood serum (t(1/2) 7 vs 1.5 h for ADP). Hence, we propose 7a as a highly promising neuroprotectant.

  DOI：

  10.1021/jm400197m

文献信息

• Highly Efficient Biocompatible Neuroprotectants with Dual Activity as Antioxidants and P2Y Receptor Agonists
  作者：Sagit Azran、Daniel Förster、Ortal Danino、Yael Nadel、Georg Reiser、Bilha Fischer

  DOI：10.1021/jm400197m

  日期：2013.6.27

  Currently, there is a need for novel, biocompatible, and effective neuroprotectants for the treatment of neurodegenerative diseases and brain injury associated with oxidative damage. Here, we developed nucleotide-based neuroprotectants acting dually as antioxidants and P2Y-R agonists. To improve the potency, selectivity, and metabolic stability of ATP/ADP, we substituted adenine C2-position by Cl and P-alpha/P-beta position by borano group, 6-9. Nucleotides 6-9 inhibited oxidation in cell-free systems (Fe(II)-H2O2), as detected by ESR (IC50 up to 175 mu M), and ABTS assay (IC50 up to 40 mu M). They also inhibited FeSO4-induced oxidative stress in PC12 cells (IC50 of 80-200 nM). 2-Cl-ADP(alpha-BH3), 7a, was found to be the most potent P2Y(1)-R agonist currently known (EC50 7 nM) and protected primary cortical neurons from FeSO4 insult (EC50 170 nM). In addition, it proved to be metabolically stable in human blood serum (t(1/2) 7 vs 1.5 h for ADP). Hence, we propose 7a as a highly promising neuroprotectant.