5-fluoro-4-methoxy-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine | 952429-14-0

• 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
• 英文名称: 5-fluoro-4-methoxy-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 4-methoxy-5-fluoro-N7-(β-D-ribofuranosyl)-pyrrolo[2,3-d]pyrimidine；(2R,3R,4S,5R)-2-(5-Fluoro-4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol；(2R,3R,4S,5R)-2-(5-fluoro-4-methoxypyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 952429-14-0
• 化学式: C₁₂H₁₄FN₃O₅
• 分子量: 299.259
• InChiKey: PXIHWDCNOUSGCQ-WOUKDFQISA-N

物化性质

• 沸点：
  591.0±50.0 °C(Predicted)
• 密度：
  1.78±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-fluoro-4-methoxy-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine 在 吡啶 、 咪唑 、 碘代三甲硅烷 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 27.0h， 生成 7-(5-O-(bis(4-methoxyphenyl)(phenyl)methyl)-3-O-(tert-butyl(dimethyl)silyl)-beta-D-ribofuranosyl)-5-fluoro-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
  参考文献：
  名称：

  肿瘤免疫类化合物及其应用

  摘要：

  肿瘤免疫类化合物及其应用。本发明公开了式(Ⅰ)所示化合物、其光学异构体及其药效上可接受的盐，以及该化合物作为STING激动剂的应用。。

  公开号：

  CN111349132B
• 作为产物：
  描述：

  1-乙酰基-三-苄氧基-罗伯糖 在 N,O-双三甲硅基乙酰胺 作用下， 以 乙腈 为溶剂， 反应 1.14h， 生成 5-fluoro-4-methoxy-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  CYCLIC DINUCLEOTIDE COMPOUND AND USES THEREOF

  摘要：

  提供的是化合物（I）的化学式，其光学异构体，其药用盐，以及作为STING激动剂的该化合物的用途。

  公开号：

  US20210340169A1

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。
• 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.
• Fluorine Substituted Adenosines As Probes of Nucleobase Protonation in Functional RNAs
  作者：Ian T. Suydam、Scott A. Strobel

  DOI：10.1021/ja803336y

  日期：2008.10.15

  Ionized nucleobases are required for folding, conformational switching, or catalysis in a number of functional RNAs. A common strategy to study these sites employs nucleoside analogues with perturbed pK(a), but the interpretation of these studies is often complicated by the chemical modification introduced, in particular modifications that add, remove, or translocate hydrogen bonding groups in addition to perturbing pKa values. In the present study we present a series of fluorine substituted adenosine analogues that produce large changes in N1 pK(a) values with minimal structural perturbation. These analogues include fluorine for hydrogen substitutions in the adenine ring of adenosine and 7-deaza-adenosine with resulting N1 pK(a) values spanning more than 4 pKa units. To demonstrate the utility of these analogues we have conducted a nucleotide analogue interference mapping (NAIM) study on a self-ligating construct of the Varkud Satellite (VS) ribozyme. We find that each of the analogues is readily incorporated by T7 RNA polymerase and produces fully active transcripts when substituted at the majority of sites. Strong interferences are observed for three sites known to be critical for VS ribozyme function, most notably A756. Substitutions at A756 lead to slight enhancements in activity for elevated pK(a) analogues and dramatic interferences in activity for reduced pK(a) analogues, supporting the proposed catalytic role for this base. The structural similarity of these analogues, combined with their even incorporation and selective interference, provides an improved method for identifying sites of adenosine protonation in a variety of systems.