9-[(3aR,4R,6R,6aR)-6-(dianilinophosphoryloxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-bromo-1-(2-hydroxyethoxymethyl)purin-6-one | 444989-17-7

• 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: 9-[(3aR,4R,6R,6aR)-6-(dianilinophosphoryloxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-bromo-1-(2-hydroxyethoxymethyl)purin-6-one
• CAS: 444989-17-7
• 化学式: C₂₈H₃₂BrN₆O₈P
• 分子量: 691.475
• InChiKey: FCPQPBYRIZJFKW-HUBRGWSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  44
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  158
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  9-[(3aR,4R,6R,6aR)-6-(dianilinophosphoryloxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-bromo-1-(2-hydroxyethoxymethyl)purin-6-one 在 吡啶 、 四氮唑 、 异戊腈 、 3 A molecular sieve 、 triisopropylbenzenesulfonyl chloride 、 碘 、 乙酸酐 、 溶剂黄146 作用下， 以 吡啶 为溶剂， 反应 31.0h， 生成 N¹-[(5''-O-phosphorylethoxy)methyl]-2',3'-O-isopropylidene 5'-O-phosphoryl-8-bromoinosine 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]-2',3'-O-isopropylideneinosine 在 吡啶 、 四氮唑 、 甲醇 、 sodium methylate 作用下， 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-bromo-1-(2-hydroxyethoxymethyl)purin-6-one
  参考文献：
  名称：

  Chemical synthesis and calcium release activity of N 1 -ether strand substituted cADPR mimic

  摘要：

  8-Chloro cyclic inosine 5'-diphosphate ethoxymethyl ether 3 was synthesized by means of chemical method from protected inosine via phenylthio-type biphosphate substrate. The detection of Ca2+ release activity shows that 3 is a potent agonist of cADPR and has activity in intact Hela cells. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00033-1

文献信息

• Chemical synthesis and calcium release activity of N 1 -ether strand substituted cADPR mimic
  作者：Li-Jun Huang、Yong-Yuan Zhao、Lan Yuan、Ji-Mei Min、Li-He Zhang

  DOI：10.1016/s0960-894x(02)00033-1

  日期：2002.3

  8-Chloro cyclic inosine 5'-diphosphate ethoxymethyl ether 3 was synthesized by means of chemical method from protected inosine via phenylthio-type biphosphate substrate. The detection of Ca2+ release activity shows that 3 is a potent agonist of cADPR and has activity in intact Hela cells. (C) 2002 Elsevier Science Ltd. All rights reserved.
• 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.
• Syntheses and Calcium-Mobilizing Evaluations of <i>N</i>-Glycosyl-Substituted Stable Mimics of Cyclic ADP-Ribose
  作者：Li-Jun Huang、Yong-Yuan Zhao、Lan Yuan、Ji-Mei Min、Li-He Zhang

  DOI：10.1021/jm010530l

  日期：2002.11.1

  Cyclic ADP-ribose (cADPR) is not only a potent endogenous calcium modulator but also a second messenger. However, studies on the mechanism of cADPR action were limited due to its instability and lack of available structural modifications in the N-1-glyosyl unit of cADPR. In the present work, a series of N-1-glycosyl mimics with different configurational glycosyls or an ether strand were designed and synthesized mimicking the furanose ring. S(N)2 substitutions were carried out between the protected inosine and glycosyl triflates to form the N-1-glycosylinosine derivatives, accompanied with some O-6-glyeosyl-substituted as side products. The intramolecular cyclization was followed the strategy described by Matsuda et al. It was found that the 8-unsubstituted substrate could also be used to construct the intramolecular cyclic pyrophosphate. The activities of NI-glycosyl-substituted cADPR mimics were evaluated by induced Ca2+ release in rat brain microsomes and HeLa cells. It was found that the configuration of the N-1-glycosyl moiety in cADPR is not a critical structural factor for retaining the activity of mobilizing Ca2+ release. More interestingly, the N-1-acyclic analogue 6 exhibited strong activity by inducing Ca2+ release in both rat brain microsomes and HeLa cells. It constitutes a useful tool for further studies.