N¹-[[[bis-5''-(phenylthio)phosphoryl]oxyethoxy]methyl]-5'-O-dianilinophosphoryl-2',3'-O-isopropylidene-8-azidoinosine | 799815-65-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: N¹-[[[bis-5''-(phenylthio)phosphoryl]oxyethoxy]methyl]-5'-O-dianilinophosphoryl-2',3'-O-isopropylidene-8-azidoinosine
• 英文别名: 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-bis(phenylsulfanyl)phosphoryloxyethoxymethyl]purin-6-one
• CAS: 799815-65-9
• 化学式: C₄₀H₄₁N₉O₉P₂S₂
• 分子量: 917.9
• InChiKey: FIDHEKATKISEAD-NFXQKKKASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  62
• 可旋转键数：
  19
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  229
• 氢给体数：
  2
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  N¹-[[[bis-5''-(phenylthio)phosphoryl]oxyethoxy]methyl]-5'-O-dianilinophosphoryl-2',3'-O-isopropylidene-8-azidoinosine 在 吡啶 、 甲酸 、 异戊腈 、 3 A molecular sieve 、 碘 、 乙酸酐 、 溶剂黄146 作用下， 以 吡啶 为溶剂， 反应 19.0h， 生成 N¹-[(5''-O-phosphorylethoxy)methyl]-5'-O-phosphoryl-8-azidoinosine 5',5''-cyclicpyrophosphate triethylammonium salt
  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 吡啶 、 四氮唑 、 甲醇 、 sodium azide 、 triisopropylbenzenesulfonyl chloride 、 sodium methylate 作用下， 以 二甲基亚砜 为溶剂， 反应 26.0h， 生成 N¹-[[[bis-5''-(phenylthio)phosphoryl]oxyethoxy]methyl]-5'-O-dianilinophosphoryl-2',3'-O-isopropylidene-8-azidoinosine
  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

文献信息

• Synthesis and Biological Evaluation of Novel Membrane-Permeant Cyclic ADP-Ribose Mimics:  <i>N</i>-[(5‘ ‘-<i>O</i>-Phosphorylethoxy)methyl]-5‘-<i>O</i>-phosphorylinosine 5‘,5‘ ‘-Cyclicpyrophosphate (cIDPRE) and 8-Substituted Derivatives
  作者：Xianfeng Gu、Zhenjun Yang、Liangren Zhang、Svenja Kunerth、Ralf Fliegert、Karin Weber、Andreas H. Guse、Lihe Zhang

  DOI：10.1021/jm040092t

  日期：2004.11.1

  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.