4-methyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine | 1256159-09-7

• 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-methyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 6-methyl-9β-D-ribofuranosyl-7-deazapurine；4-Methyl-7-(beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(4-methylpyrrolo[2,3-d]pyrimidin-7-yl)oxolane-3,4-diol
• CAS: 1256159-09-7
• 化学式: C₁₂H₁₅N₃O₄
• 分子量: 265.269
• InChiKey: TWVNSMOKOGLVNT-DNRKLUKYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  4-methyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine 在 N-碘代丁二酰亚胺 、 sodium thiomethoxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以58%的产率得到5-iodo-4-methyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  NOVEL SUBSTITUTED 7-DEAZAPURINE RIBONUCLEOSIDES FOR THERAPEUTIC USES

  摘要：

  化合物I的盐，其药用上可以接受的盐，其光学异构体或其光学异构体的混合物，以及包括这些化合物的组合物和利用这些化合物和/或组合物的治疗方法。

  公开号：

  US20160159844A1
• 作为产物：
  描述：

  4-chloro-7-β-D-ribofuranosylpyrrolo<2,3-d>pyrimidine 在 吡啶 、 四(三苯基膦)钯 、 氨 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 15.0h， 生成 4-methyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue Viruses

  摘要：

  Bioisosteric deaza analogues of 6-methyl-9-beta-D-ribofuranosylpurine, a hydrophobic analogue of adenosine, were synthesized and evaluated for antiviral activity. Whereas the 1-deaza and 3-deaza analogues were essentially inactive in plaque assays of infectivity, a novel 7-deaza-6-methyl-9-beta-D-ribofuranosylpurine analogue, structurally related to the natural product tubercidin, potently inhibited replication of poliovirus (PV) in HeLa cells (IC50 = 11 nM) and dengue virus (DENV) in Vero cells (IC50 = 62 nM). Selectivity against PV over cytotoxic effects to HeLa cells was > 100-fold after incubation for 7 h. Mechanistic studies of the 5'-triphosphate of 7-deaza-6-methyl-9-beta-D-riboluranosylpurine revealed that this compound is an efficient substrate of PV RNA-dependent RNA polymerase (RdRP) and is incorporated into RNA mimicking both ATP and GTP.

  DOI：

  10.1021/jm100593s

文献信息

• Iron/Copper Co-Catalyzed Cross-Coupling Reaction for the Synthesis of 6-Substituted 7-Deazapurines and the Corresponding Nucleosides
  作者：Qingfeng Li、Leentje Persoons、Dirk Daelemans、Piet Herdewijn

  DOI：10.1021/acs.joc.9b02414

  日期：2020.1.17

  to 6-substituted 7-deazapurine and the corresponding nucleosides by coupling aryl or alkyl Grignard reagents and halogenated purine nucleosides in the presence of Fe(acac)3/CuI is described. A series of 6-substituted 7-deazapurines and the corresponding nucleosides were obtained in medium to good yields. For the synthesis of modified nucleosides that will be the subject of biological testing, we propose

  描述了通过在Fe（acac）3 / CuI存在下偶联芳基或烷基格氏试剂和卤代嘌呤核苷来有效获得6-取代的7-脱氮嘌呤和相应的核苷。以中等至良好的产率获得了一系列6-取代的7-脱氮嘌呤和相应的核苷。对于合成修饰的核苷的合成（将成为生物学测试的主题），我们建议使用铁催化而不是钯催化的反应。测试合成的化合物的抗增殖活性。化合物11a-q的细胞毒性研究表明，通过修饰7-脱氮嘌呤核糖核苷的6位，该化合物可能对某些癌细胞系具有选择性。
• NOVEL SUBSTITUTED 7-DEAZAPURINE RIBONUCLEOSIDES FOR THERAPEUTIC USES
  申请人：Institute of Organic Chemistry and Biochemistry ASCR, v.v.i.

  公开号：US20160159844A1

  公开（公告）日：2016-06-09

  Compounds of Formula I and a pharmaceutically acceptable salt thereof, an optical isomer thereof, or a mixture of optical isomers thereof, as well as compositions which include such compounds and therapeutic methods that utilize such compounds and/or compositions.

  化合物I的盐，其药用上可以接受的盐，其光学异构体或其光学异构体的混合物，以及包括这些化合物的组合物和利用这些化合物和/或组合物的治疗方法。
• US9586986B2
  申请人：——

  公开号：US9586986B2

  公开（公告）日：2017-03-07
• Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue Viruses
  作者：Runzhi Wu、Eric D. Smidansky、Hyung Suk Oh、Ratree Takhampunya、Radhakrishnan Padmanabhan、Craig E. Cameron、Blake R. Peterson

  DOI：10.1021/jm100593s

  日期：2010.11.25

  Bioisosteric deaza analogues of 6-methyl-9-beta-D-ribofuranosylpurine, a hydrophobic analogue of adenosine, were synthesized and evaluated for antiviral activity. Whereas the 1-deaza and 3-deaza analogues were essentially inactive in plaque assays of infectivity, a novel 7-deaza-6-methyl-9-beta-D-ribofuranosylpurine analogue, structurally related to the natural product tubercidin, potently inhibited replication of poliovirus (PV) in HeLa cells (IC50 = 11 nM) and dengue virus (DENV) in Vero cells (IC50 = 62 nM). Selectivity against PV over cytotoxic effects to HeLa cells was > 100-fold after incubation for 7 h. Mechanistic studies of the 5'-triphosphate of 7-deaza-6-methyl-9-beta-D-riboluranosylpurine revealed that this compound is an efficient substrate of PV RNA-dependent RNA polymerase (RdRP) and is incorporated into RNA mimicking both ATP and GTP.
• Synthesis, Cytostatic, Antimicrobial, and Anti-HCV Activity of 6-Substituted 7-(Het)aryl-7-deazapurine Ribonucleosides
  作者：Petr Nauš、Olga Caletková、Petr Konečný、Petr Džubák、Kateřina Bogdanová、Milan Kolář、Jana Vrbková、Lenka Slavětínská、Eva Tloušt’ová、Pavla Perlíková、Marián Hajdúch、Michal Hocek

  DOI：10.1021/jm4018948

  日期：2014.2.13

  A series of 80 7-(het)aryl- and 7-ethyny1-7-deazapurine ribonucleosides bearing a methoxy, methylsulfanyl, methylamino, dimethylamino, methyl, or oxo group at position 6, or 2,6-disubstituted derivatives bearing a methyl or amino group at position 2, were prepared, and the biological activity of the compounds was studied and compared with that of the parent 7-(het)ary1-7-deazaadenosine series. Several of the compounds, in particular 6-substituted 7-deazapurine derivatives bearing a furyl or ethynyl group at position 7, were significantly cytotoxic at low nanomolar concentrations whereas most were much less potent or inactive. Promising activity was observed with some compounds against Mycobacterium bovis and also against hepatitis C virus in a replicon assay.