7-Deazanebularin | 16754-83-9

• 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: 7-Deazanebularin
• 英文别名: 7beta-D-Ribofuranosylpyrrolo-(2,3-d)pyrimidine；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-pyrrolo[2,3-d]pyrimidin-7-yloxolane-3,4-diol
• CAS: 16754-83-9
• 化学式: C₁₁H₁₃N₃O₄
• 分子量: 251.242
• InChiKey: AAVNIPCGOZFQJG-TURQNECASA-N

物化性质

• 沸点：
  567.0±50.0 °C(Predicted)
• 密度：
  1.75±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  18
• 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：
  101
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-Deazanebularin 在 N-碘代丁二酰亚胺 、 trisodium tris(3-sulfophenyl)phosphine 、 palladium diacetate 、 sodium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.0h， 生成 5-(4-chlorophenyl)-N7-(β-D–ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  6‐Methyl‐7‐Aryl‐7‐Deazapurine Nucleosides as Anti‐ Trypanosoma cruzi Agents: Structure‐Activity Relationship and in vivo Efficacy

  摘要：

  AbstractChagas disease is a tropical infectious disease resulting in progressive organ‐damage and currently lacks efficient treatment and vaccine options. The causative pathogen, Trypanosoma cruzi, requires uptake and processing of preformed purines from the host because it cannot synthesize these de novo, instigating the evaluation of modified purine nucleosides as potential trypanocides. By modifying the pyrimidine part of a previously identified 7‐aryl‐7‐deazapurine nucleoside, we found that substitution of a 6‐methyl for a 6‐amino group allows retaining T. cruzi amastigote growth inhibitory activity but confers improved selectivity towards mammalian cells. By keeping the 6‐methyl group unaltered, and introducing different 7‐aryl groups, we identified several analogues with sub‐micromolar antitrypanosomal activity. The 7‐(4‐chlorophenyl) analogue 14, which was stable in microsomes, was evaluated in an acute mouse model. Oral administration of 25 mg/kg b.i.d. suppressed peak parasitemia and protected mice from infection‐related mortality, gave similar reductions as the reference drug of blood parasite loads determined by qPCR, but as benznidazole failed to induce sterile cure in the short time period of drug exposure (5 days).

  DOI：

  10.1002/cmdc.202100144
• 作为产物：
  描述：

  4-chloro-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine 在 甲醇 、 10 wt% Pd(OH)2 on carbon 、 氢气 、 potassium carbonate 作用下， 反应 2.0h， 以84%的产率得到7-Deazanebularin
  参考文献：
  名称：

  6‐Methyl‐7‐Aryl‐7‐Deazapurine Nucleosides as Anti‐ Trypanosoma cruzi Agents: Structure‐Activity Relationship and in vivo Efficacy

  摘要：

  AbstractChagas disease is a tropical infectious disease resulting in progressive organ‐damage and currently lacks efficient treatment and vaccine options. The causative pathogen, Trypanosoma cruzi, requires uptake and processing of preformed purines from the host because it cannot synthesize these de novo, instigating the evaluation of modified purine nucleosides as potential trypanocides. By modifying the pyrimidine part of a previously identified 7‐aryl‐7‐deazapurine nucleoside, we found that substitution of a 6‐methyl for a 6‐amino group allows retaining T. cruzi amastigote growth inhibitory activity but confers improved selectivity towards mammalian cells. By keeping the 6‐methyl group unaltered, and introducing different 7‐aryl groups, we identified several analogues with sub‐micromolar antitrypanosomal activity. The 7‐(4‐chlorophenyl) analogue 14, which was stable in microsomes, was evaluated in an acute mouse model. Oral administration of 25 mg/kg b.i.d. suppressed peak parasitemia and protected mice from infection‐related mortality, gave similar reductions as the reference drug of blood parasite loads determined by qPCR, but as benznidazole failed to induce sterile cure in the short time period of drug exposure (5 days).

  DOI：

  10.1002/cmdc.202100144

文献信息

• [EN] COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATING VIRAL INFECTION<br/>[FR] COMPOSÉS, COMPOSITIONS, ET PROCÉDÉS POUR LE TRAITEMENT D'UNE INFECTION VIRALE
  申请人：CHIMERIX INC

  公开号：WO2010135520A1

  公开（公告）日：2010-11-25

  The present invention describes compounds of formulae I and II and methods for treating viral infection, such as Flaviviridae virus infection, including Hepatitis C infection (HCV).

  本发明描述了式I和式II的化合物以及治疗病毒感染的方法，例如黄病毒科病毒感染，包括丙型肝炎病毒感染（HCV）。
• Biochemical and biological properties of 5-bromotubercidin: Differential effects on cellular DNA-directed and viral RNA-directed RNA synthesis
  作者：Branko Brdar、Edward Reich

  DOI：10.1016/j.bmc.2007.10.054

  日期：2008.2.1

  We have studied the biochemical and biological properties of 5-bromotubercidin (4-amino-5-bromo-7-beta-d-ribofuranosyl-pyrrolo [2,3-d]pyrimidine) (BrTu), a synthetic analogue of the highly cytotoxic pyrrolo[2,3-d]pyrimidine ribonucleoside antibiotic tubercidin (Tu) that interferes with numerous cellular processes, and has been shown to possess biological specificity and selectivity. Thus, BrTu entered

  我们已经研究了5-溴微球菌素（4-氨基-5-溴-7-β-d-呋喃呋喃糖基-吡咯并[2,3-d]嘧啶）（BrTu）的生物化学和生物学特性，该类似物具有高度的细胞毒性。吡咯并[2,3-d]嘧啶核糖核苷酸抗生素结核菌素（Tu）干扰许多细胞过程，并已显示具有生物学特异性和选择性。因此，BrTu通过磷酸化进入哺乳动物细胞核苷酸库，以未修饰的形式掺入RNA中，因此可逆地抑制（15 microM）哺乳动物细胞生长和高分子量细胞RNA种类（即mRNA和rRNA）。但是，BrTu（300 microM）不能抑制小核糖核酸病毒RNA的合成或繁殖，从而区分病毒RNA依赖型和DNA依赖的各种形式的RNA合成，无论是细胞来源还是病毒来源；因此，BrTu作为研究细胞与病毒关系的代谢探针应被证明是有价值的。此外，BrTu是腺苷激酶的底物（K（m）= 24 microM），也是其有效的抑制剂（K（i）= 0.93 microM）。因此，低浓度的BrTu（1
• Nucleoside compounds for treating viral infections
  申请人：Roberts D. Christopher

  公开号：US20060079468A1

  公开（公告）日：2006-04-13

  Disclosed are compounds, compositions and methods for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus.

  本发明涉及一种用于治疗由黄病毒科病毒引起的病毒感染的化合物、组合物和方法，例如丙型肝炎病毒。
• NOVEL CYTOSTATIC 7-DEAZAPURINE NUCLEOSIDES
  申请人：INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY OF THE ACADEMY OF SCIENCES OF THE CZECH REPUBLIC

  公开号：EP3133080A1

  公开（公告）日：2017-02-22

  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.

  本发明提供了式 I 的化合物（其中 R1 和 R2 具有说明书中定义的任何值）及其盐类，以及包含此类化合物的组合物和利用此类化合物的治疗方法。
• Reductive Deamination of Aminopurine Nucleosides
  作者：Vasu Nair、Stanley D. Chamberlain

  DOI：10.1055/s-1984-30851

  日期：——