4-methoxy-5-chloro-N7-(β-D-ribofuranosyl)-pyrrolo[2,3-d]pyrimidine | 952429-15-1

• 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-methoxy-5-chloro-N7-(β-D-ribofuranosyl)-pyrrolo[2,3-d]pyrimidine
• 英文别名: (2R,3R,4S,5R)-2-(5-chloro-4-methoxypyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 952429-15-1
• 化学式: C₁₂H₁₄ClN₃O₅
• 分子量: 315.713
• InChiKey: FJZUKNINYAACNU-WOUKDFQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 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：
  7

反应信息

• 作为反应物：
  描述：

  4-methoxy-5-chloro-N7-(β-D-ribofuranosyl)-pyrrolo[2,3-d]pyrimidine 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 4.0h， 以33%的产率得到5-chloro-3,7-dihydro-7-(β-D-ribofuranosyl)-4H-pyrrolo[2,3-d]pyrimidin-4-one
  参考文献：
  名称：

  C6-O-烷基化的7-脱氮芥子苷核苷类似物：发现有效的和选择性的抗睡眠病药物。

  摘要：

  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。

  DOI：

  10.1016/j.ejmech.2019.112018
• 作为产物：
  描述：

  在 甲醇 、 三氟甲磺酸三甲基硅酯 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 4-methoxy-5-chloro-N7-(β-D-ribofuranosyl)-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] 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。
• 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。
• NUCLEOSIDE ANALOGUES FOR THE TREATMENT OF PARASITIC INFECTIONS
  申请人：UNIVERSITEIT GENT

  公开号：US20210024566A1

  公开（公告）日：2021-01-28

  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.