4,5-dichloro-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine | 952429-08-2

• 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: 4,5-dichloro-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: [(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(4,5-dichloropyrrolo[2,3-d]pyrimidin-7-yl)oxolan-2-yl]methyl benzoate
• CAS: 952429-08-2
• 化学式: C₃₂H₂₃Cl₂N₃O₇
• 分子量: 632.457
• InChiKey: ZPOYWLXTRNFCAQ-CTDWIVFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  119
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4,5-dichloro-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine 在 氨 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以84%的产率得到5-氯杀结核菌素
  参考文献：
  名称：

  C7修饰的4-氨基-吡咯并[2,1-f] [1,2,4]三嗪C-核苷的抗诺如病毒活性。

  摘要：

  以CC异头键为特征的合成核苷类似物形成了一个有前途的针对传染性和恶性疾病的疗法。本文中，检查了在糖和核碱基部分包含结构变异的C-核苷抑制鼠和人诺如病毒RNA依赖性RNA聚合酶（RdRp）的能力。我们发现4-氨基-吡咯并[2,1-f] [1,2,4]三嗪及其7-卤代同族与d-核糖或2'-C-甲基-d-核糖的组合该单元产生了对鼠诺如病毒（MNV）具有良好抗病毒活性的类似物，尽管其具有明显的细胞毒性。在该系列中，4-氮杂-7,9-二氮杂叠氮腺苷在人诺如病毒（HuNoV）复制子测定中的EC50 = 0.015μM时特别保留了强大的抗病毒作用。

  DOI：

  10.1016/j.ejmech.2020.112198
• 作为产物：
  描述：

  4,5-二氯-7H-吡咯并[2,3-D]嘧啶 在 三氟甲磺酸三甲基硅酯 作用下， 以 乙腈 为溶剂， 反应 1.17h， 生成 4,5-dichloro-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.tet.2007.06.107

文献信息

• [EN] NOVEL CYTOSTATIC 7-DEAZAPURINE NUCLEOSIDES<br/>[FR] NOUVEAUX NUCLÉOSIDES 7-DÉAZAPURINE CYTOSTATIQUES
  申请人：ACAD OF SCIENCE CZECH REPUBLIC

  公开号：WO2009089804A1

  公开（公告）日：2009-07-23

  The invention provides compounds of formula (I), wherein R1 and R2 have any of the values defined in the specification and salts thereof, as well as compositions comprising such compounds and therapeutic methods that utilize such compounds.

  这项发明提供了式（I）的化合物，其中R1和R2具有规范中定义的任何值及其盐，以及包含这些化合物的组合物和利用这些化合物的治疗方法。
• 6-Alkyl-, 6-aryl- or 6-hetaryl-7-deazapurine ribonucleosides as inhibitors of human or MTB adenosine kinase and potential antimycobacterial agents
  作者：Pavla Perlíková、Petr Konečný、Petr Nauš、Jan Snášel、Ivan Votruba、Petr Džubák、Iva Pichová、Marián Hajdúch、Michal Hocek

  DOI：10.1039/c3md00232b

  日期：——

  Title 6-alkyl-, 6-aryl- and 6-hetaryl-7-deazapurine ribonucleosides previously known as nanomolar cytostatics were found to be potent inhibitors of either human or mycobacterial (MTB) adenosine kinase (ADK). Several new derivatives bearing bulky substituents at position 6 were non-cytotoxic but selectively inhibited MTB ADK. However, most of the nucleosides (ADK inhibitors) as well as their octadecylphosphate prodrugs were inactive in the whole cell assay of inhibition of Mycobacterium bovis growth. 6-Methyl-7-deazapurine ribonucleoside was found to be a potent antimycobacterial agent.

  标题：6-烷基、6-芳基和6-杂芳基-7-脱氮嘌呤核糖核苷，先前被称为纳摩尔级的细胞抑制剂，被发现是强效的人类或分枝杆菌（MTB）腺苷激酶（ADK）抑制剂。一些在6位带有大体积取代基的新衍生物无细胞毒性，但能选择性地抑制MTB ADK。然而，大多数核苷（ADK抑制剂）及其十八烷基磷酸前药在抑制牛分枝杆菌生长的整体细胞试验中均无活性。6-甲基-7-脱氮嘌呤核糖核苷被发现是一种强效的抗分枝杆菌剂。
• [EN] NUCLEOSIDE ANALOGUES FOR THE TREATMENT OF PARASITIC INFECTIONS<br/>[FR] ANALOGUES DE NUCLÉOSIDE POUR LE TRAITEMENT D'INFECTIONS PARASITAIRES
  申请人：UNIV GENT

  公开号：WO2019076633A1

  公开（公告）日：2019-04-25

  The present invention relates to novel nucleoside analogues and compositions containing said nucleoside analogues. Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the diagnosis, prevention and/or treatment of parasitic infections, more specifically for use in the diagnosis, prevention and/or treatment of a Trypanosoma infection.

  本发明涉及新型核苷类似物和含有所述核苷类似物的组合物。此外，本发明提供了制备所述化合物的方法，以及使用它们的方法，例如作为药物，特别是用于诊断、预防和/或治疗寄生虫感染，更具体地用于诊断、预防和/或治疗Trypanosoma感染。
• 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。
• Nucleoside analogues for the treatment of parasitic infections
  申请人：UNIVERSITEIT GENT

  公开号：US11072628B2

  公开（公告）日：2021-07-27

  The present invention relates to novel nucleoside analogues and compositions containing said nucleoside analogues. Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the diagnosis, prevention and/or treatment of parasitic infections, more specifically for use in the diagnosis, prevention and/or treatment of a Trypanosoma infection.

  本发明涉及新型核苷类似物和含有所述核苷类似物的组合物。 此外，本发明还提供了所公开化合物的制备工艺以及使用方法，例如将其用作药物，特别是用于诊断、预防和/或治疗寄生虫感染，更具体地说是用于诊断、预防和/或治疗锥虫感染。