4-methyl-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine | 1536110-54-9

• 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: 4-methyl-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 4-Methyl-7-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine；[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(4-methylpyrrolo[2,3-d]pyrimidin-7-yl)oxolan-2-yl]methyl benzoate
• CAS: 1536110-54-9
• 化学式: C₃₃H₂₇N₃O₇
• 分子量: 577.593
• InChiKey: RQGNPONVRNOFGY-NODMTMHWSA-N

物化性质

• 沸点：
  741.7±60.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.18
• 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-methyl-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  6-甲基7位脱氮嘌呤核苷类化合物及其用途

  摘要：

  本发明公开了一种6‑甲基7位脱氮嘌呤核苷类化合物及其用途，属于药物化学领域。本发明的具有式I结构特征的6‑甲基7位脱氮嘌呤核苷类化合物或者其药学上可接受的盐，是依据RNA病毒聚合酶的蛋白结构特征，设计和合成的一类新结构的化合物，该类化合物能够抑制RNA病毒，从而可以做为预防和治疗如HCV,流感病毒，HRV(鼻病毒)，RSV，Ebola病毒，登革热病毒以及肠道病毒等RNA病毒感染的潜在药物。

  公开号：

  CN107033206B
• 作为产物：
  描述：

  4-氯-5-碘-7H-吡咯并[2,3-d]嘧啶 在 copper(l) iodide 、 lithium chloro-isopropyl-magnesium chloride 、 iron(III)-acetylacetonate 、 三氟甲磺酸三甲基硅酯 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 乙腈 为溶剂， 反应 3.0h， 生成 4-methyl-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  铁/铜共催化的交叉偶联反应，用于合成6-取代的7-脱氮嘌呤和相应的核苷。

  摘要：

  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。

  DOI：

  10.1021/acs.joc.9b02414

文献信息

• [EN] NOVEL 6-SUBSTITUTED 7-DEAZAPURINES AND CORRESPONDING NUCLEOSIDES AS MEDICAMENTS<br/>[FR] NOUVELLES 7-DÉAZAPURINES 6-SUBSTITUÉES ET NUCLÉOSIDES CORRESPONDANTS EN TANT QUE MÉDICAMENTS
  申请人：UNIV LEUVEN KATH

  公开号：WO2021164848A1

  公开（公告）日：2021-08-26

  The present invention relates to the synthesis of 6-substituted 7-deazapurines and their corresponding nucleosides by coupling aryl or alkyl Grignard reagents with halogenated purine nucleosides in the presence of iron or an iron/copper mixture such as Fe(acac)3/Cul. The present invention also relates to pharmaceutical compositions comprising said compounds and the use of said pharmaceutical compositions to treat or prevent viral infections.

  本发明涉及通过在铁或铁/铜混合物（如Fe(acac)3/Cul）存在下，将芳基或烷基格氏试剂与卤代嘌呤核苷酸偶联来合成6-取代7-脱氮嘌呤及其相应的核苷的方法。本发明还涉及包括所述化合物的药物组合物以及利用所述药物组合物治疗或预防病毒感染的用途。
• 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).
• 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.
• US9586986B2
  申请人：——

  公开号：US9586986B2

  公开（公告）日：2017-03-07