5-iodo-4-methylsulfanyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine | 144928-11-0

• 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-iodo-4-methylsulfanyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: (2R,3S,4R,5R)-2-(hydroxymethyl)-5-(5-iodo-4-methylsulfanyl-pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuran-3,4-diol；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(5-iodo-4-methylsulfanylpyrrolo[2,3-d]pyrimidin-7-yl)oxolane-3,4-diol
• CAS: 144928-11-0
• 化学式: C₁₂H₁₄IN₃O₄S
• 分子量: 423.231
• InChiKey: NHBDQJUSBFAFSA-WOUKDFQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 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：
  126
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-iodo-4-methylsulfanyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine 在 甲醇 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 potassium carbonate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 5-ethynyl-4-methylsulfanyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Synthesis, Cytostatic, Antimicrobial, and Anti-HCV Activity of 6-Substituted 7-(Het)aryl-7-deazapurine Ribonucleosides

  摘要：

  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.

  DOI：

  10.1021/jm4018948
• 作为产物：
  描述：

  (2R,3R,4R,5R)-2-((苯甲酰氧基)甲基)-5-(4-氯-5-碘-7H-吡咯并[2 、 sodium thiomethoxide 以 乙醇 为溶剂， 反应 4.0h， 以94%的产率得到5-iodo-4-methylsulfanyl-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

文献信息

• 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。
• 6‐Methyl‐7‐Aryl‐7‐Deazapurine Nucleosides as Anti‐ <i>Trypanosoma cruzi</i> Agents: Structure‐Activity Relationship and <i>in vivo</i> Efficacy
  作者：Cai Lin、Ludmila Ferreira de Almeida Fiuza、Camila Cardoso Santos、Daniela Ferreira Nunes、Otacílio Cruz Moreira、Jakob Bouton、Izet Karalic、Louis Maes、Guy Caljon、Fabian Hulpia、Maria Nazaré C. Soeiro、Serge Van Calenbergh

  DOI：10.1002/cmdc.202100144

  日期：2021.7.20

  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).
• US9586986B2
  申请人：——

  公开号：US9586986B2

  公开（公告）日：2017-03-07
• 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.