2-[[9-[(3aR,4R,6R,6aR)-6-(dianilinophosphoryloxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-azido-6-oxopurin-1-yl]methoxy]ethyl acetate | 799815-62-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: 2-[[9-[(3aR,4R,6R,6aR)-6-(dianilinophosphoryloxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-azido-6-oxopurin-1-yl]methoxy]ethyl acetate
• CAS: 799815-62-6
• 化学式: C₃₀H₃₄N₉O₉P
• 分子量: 695.629
• InChiKey: DAUVGDIAYUSFCG-ZYWWQZICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  49
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  178
• 氢给体数：
  2
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  2-[[9-[(3aR,4R,6R,6aR)-6-(dianilinophosphoryloxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-azido-6-oxopurin-1-yl]methoxy]ethyl acetate 在 甲醇 、 sodium methylate 作用下， 反应 2.0h， 生成 9-[(3aR,4R,6R,6aR)-6-(dianilinophosphoryloxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-azido-1-(2-hydroxyethoxymethyl)purin-6-one
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Membrane-Permeant Cyclic ADP-Ribose Mimics:  N-[(5‘ ‘-O-Phosphorylethoxy)methyl]-5‘-O-phosphorylinosine 5‘,5‘ ‘-Cyclicpyrophosphate (cIDPRE) and 8-Substituted Derivatives

  摘要：

  N-1- [(5"-O-Phosphorylethoxy)methyl] -5'-O-phosphorylinosine 5',5"-cyclicpyrophosphate (cIDPRE 2a) and the 8-substituted derivatives 8-bromo-, 8-azido-, 8-amino-, and 8-Cl-cIDPRE (2b-e) were synthesized from N1- [(5"-acetoxyethoxy)methyl] -2',3'-O-isopropylideneinosine (5) in good yields. The pharmacological activities of cIDPRE and the 8-substituted derivatives (2a-e) were analyzed in intact and permeabilized. human Jurkat T-lymphocytes. The results indicate that cIDPRE permeates the plasma membrane, releases Ca2+ from an intracellular, cADPR-sensitive Ca2+ store, and subsequently initiates Ca2+ release-activated Ca2+ entry. The Ca2+-releasing activity of cIDPRE was confirmed directly in permeabilized. cells. Using time-resolved confocal Ca2+ imaging at the single cell level, the development of global Ca2+ signals starting from local small Ca2+ signals evoked by cIDPRE was observed. 8-N-3-cIDPRE 2c and 8-NH2-cIDPRE 2d were similarly effective in their agonistic activity as compared to cIDPRE 2a, showing almost indistinguishable concentration-response curves for 2a, 2c, and 2d and very similar kinetics of Ca2+ signaling. In contrast, the halogenated derivatives 8-Br- and 8-Cl-cIDPRE (2b and 2e) did not significantly elevate [Ca2+](i). Therefore, cIDPRE 2a, 8-N-3-cIDPRE 2c, and 8-NH2-cIDPRE 2d are novel membrane permeant cADPR mimic and may provide important novel tools to study cADPR-mediated Ca2+ signaling in intact cells.

  DOI：

  10.1021/jm040092t
• 作为产物：
  描述：

  8-bromo-N¹-[(2-acetoxyethoxy)-methyl]-5'-O-dianilinophosphoryl-2',3'-O-isopropylideneinosine 在 sodium azide 作用下， 以 二甲基亚砜 为溶剂， 反应 12.0h， 以90%的产率得到2-[[9-[(3aR,4R,6R,6aR)-6-(dianilinophosphoryloxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-azido-6-oxopurin-1-yl]methoxy]ethyl acetate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Membrane-Permeant Cyclic ADP-Ribose Mimics:  N-[(5‘ ‘-O-Phosphorylethoxy)methyl]-5‘-O-phosphorylinosine 5‘,5‘ ‘-Cyclicpyrophosphate (cIDPRE) and 8-Substituted Derivatives

  摘要：

  N-1- [(5"-O-Phosphorylethoxy)methyl] -5'-O-phosphorylinosine 5',5"-cyclicpyrophosphate (cIDPRE 2a) and the 8-substituted derivatives 8-bromo-, 8-azido-, 8-amino-, and 8-Cl-cIDPRE (2b-e) were synthesized from N1- [(5"-acetoxyethoxy)methyl] -2',3'-O-isopropylideneinosine (5) in good yields. The pharmacological activities of cIDPRE and the 8-substituted derivatives (2a-e) were analyzed in intact and permeabilized. human Jurkat T-lymphocytes. The results indicate that cIDPRE permeates the plasma membrane, releases Ca2+ from an intracellular, cADPR-sensitive Ca2+ store, and subsequently initiates Ca2+ release-activated Ca2+ entry. The Ca2+-releasing activity of cIDPRE was confirmed directly in permeabilized. cells. Using time-resolved confocal Ca2+ imaging at the single cell level, the development of global Ca2+ signals starting from local small Ca2+ signals evoked by cIDPRE was observed. 8-N-3-cIDPRE 2c and 8-NH2-cIDPRE 2d were similarly effective in their agonistic activity as compared to cIDPRE 2a, showing almost indistinguishable concentration-response curves for 2a, 2c, and 2d and very similar kinetics of Ca2+ signaling. In contrast, the halogenated derivatives 8-Br- and 8-Cl-cIDPRE (2b and 2e) did not significantly elevate [Ca2+](i). Therefore, cIDPRE 2a, 8-N-3-cIDPRE 2c, and 8-NH2-cIDPRE 2d are novel membrane permeant cADPR mimic and may provide important novel tools to study cADPR-mediated Ca2+ signaling in intact cells.

  DOI：

  10.1021/jm040092t