7-去氮杂肌苷 | 2862-16-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡咯并嘧啶核苷和核苷酸
• 中文名称: 7-去氮杂肌苷
• 中文别名: 7-去氮肌苷
• 英文名称: 4-Hydroxy-7-β-D-ribofuranosyl-7H-pyrrolo<2,3-d>pyrimidin
• 英文别名: Desamino-hydroxy-tubercidin；7-Deazainosine；7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3H-pyrrolo[2,3-d]pyrimidin-4-one
• CAS: 2862-16-0
• 化学式: C₁₁H₁₃N₃O₅
• 分子量: 267.241
• InChiKey: DPRSKJHWKNHBOW-KCGFPETGSA-N

物化性质

• 熔点：
  242.5°C
• 沸点：
  410.42°C (rough estimate)
• 密度：
  1.3329 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-去氮杂肌苷 在 磷酸三乙酯 、 水 、 三氯氧磷 作用下， 反应 1.25h， 以85%的产率得到7-deazainosine 5'-monophosphate
  参考文献：
  名称：

  Structural Determinants for N1/N7 Cyclization of Nicotinamide Hypoxanthine 5‘-Dinucleotide (NHD⁺) Derivatives by ADP-Ribosyl Cyclase from Aplysia californica:  Ca²⁺-Mobilizing Activity of 8-Substituted Cyclic Inosine 5‘-Diphosphoribose Analogues in T-Lymphocytes

  摘要：

  A series of nicotinamide hypoxanthine 5'-dinucleotide (NHD+) analogues modified at C-8 (2-5) and 7-deaza-NHD+ were synthesized, and cyclization in the presence of Aplysia ADP-ribosyl cyclase was studied. All 8-substituted NHD+ analogues were converted into their N1-cyclic forms by the enzyme, while in contrast, 7-deaza- NHD+ 17 was hydrolyzed into 7-deazainosine 5'-diphosphoribose (7-deaza- IDPR) 25. Correlations are made showing that the conformation of the NHD+ substrate is the key to successful cyclization. The pharmacological activities of these novel cIDPR derivatives were evaluated in both permeabilized and intact Jurkat T-lymphocytes. The results show that in permeabilized cells both 8-iodo 1g and 8-N3-N1-cIDPR 1d have an activity comparable to that of cADPR, while 8-iodo 1g and 8-phenyl-N1-cIDPR 1c have a small but significant effect in intact cells and can therefore be regarded as membrane-permeant; thus, cIDPR derivatives are emerging as important novel biological tools to study cADPR-mediated Ca2+ release in T-cells.

  DOI：

  10.1021/jm060275a
• 作为产物：
  描述：

  4-methoxy-7-(β-D-ribofuranosyl)pyrrolo<2,3-d>pyrimidine 在 三甲基氯硅烷 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以71%的产率得到7-去氮杂肌苷
  参考文献：
  名称：

  Structural Determinants for N1/N7 Cyclization of Nicotinamide Hypoxanthine 5‘-Dinucleotide (NHD⁺) Derivatives by ADP-Ribosyl Cyclase from Aplysia californica:  Ca²⁺-Mobilizing Activity of 8-Substituted Cyclic Inosine 5‘-Diphosphoribose Analogues in T-Lymphocytes

  摘要：

  A series of nicotinamide hypoxanthine 5'-dinucleotide (NHD+) analogues modified at C-8 (2-5) and 7-deaza-NHD+ were synthesized, and cyclization in the presence of Aplysia ADP-ribosyl cyclase was studied. All 8-substituted NHD+ analogues were converted into their N1-cyclic forms by the enzyme, while in contrast, 7-deaza- NHD+ 17 was hydrolyzed into 7-deazainosine 5'-diphosphoribose (7-deaza- IDPR) 25. Correlations are made showing that the conformation of the NHD+ substrate is the key to successful cyclization. The pharmacological activities of these novel cIDPR derivatives were evaluated in both permeabilized and intact Jurkat T-lymphocytes. The results show that in permeabilized cells both 8-iodo 1g and 8-N3-N1-cIDPR 1d have an activity comparable to that of cADPR, while 8-iodo 1g and 8-phenyl-N1-cIDPR 1c have a small but significant effect in intact cells and can therefore be regarded as membrane-permeant; thus, cIDPR derivatives are emerging as important novel biological tools to study cADPR-mediated Ca2+ release in T-cells.

  DOI：

  10.1021/jm060275a

文献信息

• C6–O-alkylated 7-deazainosine nucleoside analogues: Discovery of potent and selective anti-sleeping sickness agents
  作者：Fabian Hulpia、Jakob Bouton、Gustavo D. Campagnaro、Ibrahim A. Alfayez、Dorien Mabille、Louis Maes、Harry P. de Koning、Guy Caljon、Serge Van Calenbergh

  DOI：10.1016/j.ejmech.2019.112018

  日期：2020.2

  , is spread to new hosts by bites of infected tsetse flies. Currently approved therapies all have their specific drawbacks, prompting a search for novel therapeutic agents. T. brucei lacks the enzymes necessary to forge the purine ring from amino acid precursors, rendering them dependent on the uptake and interconversion of host purines. This dependency renders analogues of purines and corresponding

  非洲锥虫病是由原生动物Trypanosoma brucei spp。引起的一种致命的传染病，通过被感染的采采蝇的叮咬传播到新的寄主。目前批准的疗法都有其特定的缺点，促使人们寻找新的治疗剂。T. brucei缺乏从氨基酸前体形成嘌呤环所需的酶，使其依赖于宿主嘌呤的吸收和相互转化。这种依赖性使得嘌呤的类似物和相应的核苷成为潜在的抗-T的有趣来源。布鲁斯代理商。在这项研究中，我们合成和评估了一系列7-取代的7-脱氮芥子碱衍生物，发现6-O-烷基化的类似物特别具有极好的前景，其EC50值在纳摩尔级范围内。SAR对O-烷基链的研究表明，至少在线性烷基链系列中，随着烷基链长度的增加，抗锥虫活性以及细胞毒性也随之增加。然而，这可以通过引入末端分支点来减弱，从而产生高度有效和选择性的类似物36、37和38。无法鉴定出与转运蛋白介导的摄取相关的抗药性，这些类似物中的几种被指定用于进一步的体内跟踪研究。研究。
• Synthese von 7‐Desazainosin durch Phasentransferglycosidierung
  作者：Frank Seela、Doris Hasselmann

  DOI：10.1002/cber.19801131031

  日期：1980.10

  Synthesis of 7-Deazainosine by Phase Transfer Glycosidation

  相转移糖苷法合成7-脱氮芥子苷
• 7-Functionalized 7-deazapurine β-d and β-l-ribonucleosides related to tubercidin and 7-deazainosine: glycosylation of pyrrolo[2,3-d]pyrimidines with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d or β-l-ribofuranose
  作者：Frank Seela、Xin Ming

  DOI：10.1016/j.tet.2007.06.107

  日期：2007.9

  Several 7-functionalized 7-deazapurine ribonucleosides were prepared. Glycosylation of 7-halogenated 6-chloro-7-deazapurines with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose or 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-L-ribofuranose gave the protected beta-D-nucleosides 8c-e (53-62%) and the beta-L-nucleosides 9b-e (57-72%), which were transformed to 7-halogenated 7-deazapurine ribonucleosides related to tubercidin and 7-deazainosine. 7-Alkynyl derivatives (1f,g) and (2f,g) were obtained from the 7-iodo nucleosides 1e and 2e employing the palladium-catalyzed Sonogashira cross-coupling reaction. Within the series of 7-deazaadenosine ( tubercidin) analogues and 7-deazainosine derivatives physical data such as pK(a) values, chromatographic mobilities, C-13 NMR chemical shifts were determined and correlated to each other. (C) 2007 Elsevier Ltd. All rights reserved.
• 7-Deazainosine Derivatives: Synthesis and Characterization of 7- and 7,8-Substituted Pyrrolo [2,3-<i>d</i>]Pyrimidine Ribonucleosides
  作者：Nunzia Ciliberti、Elisa Durini、Stefano Manfredini、Silvia Vertuani

  DOI：10.1080/15257770802089009

  日期：2008.4.18

  The synthesis of model 7 deazapurine derivatives related to tubercidin and toyocamycin has been performed. Tubercidin derivatives were obtained by simple conversion of the amino group of the heterocyclic moiety of the starting 7-deazadenosine compounds, into a hydroxyl group. Preparation of toyocamycin derivatives was accomplished by treatment of the silylated 6-bromo-5-cyanopyrrolo[2,3-d]pyrimidin-4-one with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose. The glycosylation reaction afforded a mixture of 8-bromo 7-cyano 2',3',5' tri-O-benzoyl 7-deazainosine and 6-bromo-5-cyano-3-(2',3',5'-tri-O-benzoyl-beta-D-ribofuranosyl)pyrrolo[2,3-d]-pyrimidin-4-one isomers: The structures were assigned on the basis of NMR spectroscopy studies. Next deprotection treatment gave the novel 7-deazainosine ribonucleosides.
• Structural Determinants for N1/N7 Cyclization of Nicotinamide Hypoxanthine 5‘-Dinucleotide (NHD⁺) Derivatives by ADP-Ribosyl Cyclase from <i>Aplysia </i><i>californica</i>:  Ca²⁺-Mobilizing Activity of 8-Substituted Cyclic Inosine 5‘-Diphosphoribose Analogues in T-Lymphocytes
  作者：Christelle Moreau、Gerd K. Wagner、Karin Weber、Andreas H. Guse、Barry V. L. Potter

  DOI：10.1021/jm060275a

  日期：2006.8.1

  A series of nicotinamide hypoxanthine 5'-dinucleotide (NHD+) analogues modified at C-8 (2-5) and 7-deaza-NHD+ were synthesized, and cyclization in the presence of Aplysia ADP-ribosyl cyclase was studied. All 8-substituted NHD+ analogues were converted into their N1-cyclic forms by the enzyme, while in contrast, 7-deaza- NHD+ 17 was hydrolyzed into 7-deazainosine 5'-diphosphoribose (7-deaza- IDPR) 25. Correlations are made showing that the conformation of the NHD+ substrate is the key to successful cyclization. The pharmacological activities of these novel cIDPR derivatives were evaluated in both permeabilized and intact Jurkat T-lymphocytes. The results show that in permeabilized cells both 8-iodo 1g and 8-N3-N1-cIDPR 1d have an activity comparable to that of cADPR, while 8-iodo 1g and 8-phenyl-N1-cIDPR 1c have a small but significant effect in intact cells and can therefore be regarded as membrane-permeant; thus, cIDPR derivatives are emerging as important novel biological tools to study cADPR-mediated Ca2+ release in T-cells.