methyl 1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)imidazole-4,5-dicarboxylate | 66657-09-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 咪唑核糖核苷和核糖核苷酸
• 英文名称: methyl 1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)imidazole-4,5-dicarboxylate
• 英文别名: dimethyl 1-[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(benzoyloxymethyl)oxolan-2-yl]imidazole-4,5-dicarboxylate
• CAS: 66657-09-8
• 化学式: C₃₃H₂₈N₂O₁₁
• 分子量: 628.592
• InChiKey: CKQUEGAZUMRCCX-NHMNHLDDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  46
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  159
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  methyl 1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)imidazole-4,5-dicarboxylate 在 吡啶 、 甲醇 、 sodium methylate 作用下， 生成 4,5-dihydro-8H-6-(N-dodecylamino)-1-[(3',5'-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl))-β-D-ribofuranosyl]imidazo[4,5-e][1,3]diazepine-4,8-dione
  参考文献：
  名称：

  Potent Inhibition of NTPase/Helicase of the West Nile Virus by Ring-Expanded (“Fat”) Nucleoside Analogues

  摘要：

  A series of ring-expanded ("fat") nucleoside analogues (RENs) containing the 6-aminoimidazo-[4,5-e] [1,3]diazepine-4,8-dione ring system have been synthesized and screened for inhibition of NTPase/helicase of the West Nile Virus (WNV). To assess the selectivity of RENs against the viral enzymes, a truncated form of human enzyme Suv3((Delta1-159)) was also included in the study. Ring-expanded nucleosides 16, 17, and 19, which possess the long C-12, C-14, and C-18 side-chains, respectively, at position 6, as well as the ring-expanded heterocycle 39, which contains aralkyl substitution at position 1, were all found to have excellent profiles of activity and selectivity toward the viral versus human enzymes against the West Nile Virus (IC50 ranging 1-10 muM). Compound 30, while being an equally potent inhibitor of WNV, was found to be somewhat less selective, whereas compound 36, which is an alpha-anomeric counterpart of 30, exhibited potent and selective inhibition of WN-V (IC50 1-3 muM). The same compounds that showed potent inhibition of viral helicase activity completely failed to show any activity against the viral NTPase reaction even up to 500 muM. However, at concentrations >500 muM of RENs and the ATP concentrations >10 times the K-m value of the enzyme, a significant activation of NTPase activity was observed. This activating effect underwent further dramatic enhancement (>1000%) by further increases in ATP concentration in the reaction mixture, suggesting that the viral helicase and NTPase reactions are not coupled. A tentative mechanistic model has been proposed to explain the observed results.

  DOI：

  10.1021/jm030277k
• 作为产物：
  描述：

  1-乙酰氧基-2,3,5-三苯甲酰氧基-1-beta-D-呋喃核糖 、 1-trimethylsilanyl-1H-imidazole-4,5-dicarboxylic acid dimethyl ester 在 四氯化锡 作用下， 以 正己烷 、 二氯甲烷 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 生成 methyl 1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)imidazole-4,5-dicarboxylate
  参考文献：
  名称：

  Ribofuranosyl-imidazole derivatives

  摘要：

  描述了具有以下含义的化学式的核糖嘌呤-咪唑衍生物：##STR1## 这些核糖嘌呤-咪唑衍生物具有心脏和循环动力学特性，并可用于治疗心绞痛。

  公开号：

  US04115641A1

文献信息

• in vitro inhibition of the measles virus by novel ring-expanded (‘fat’) nucleoside analogues containing the imidazo[4,5-e]diazepine ring system
  作者：Ning Zhang、Huan-Ming Chen、Ramesh Sood、Kishna Kalicharran、Ali I Fattom、Robert B Naso、Dale L Barnard、Robert W Sidwell、Ramachandra S Hosmane

  DOI：10.1016/s0960-894x(02)00762-x

  日期：2002.12

  activity in African green monkey kidney cells (CV-1), employing ribavirin as the control standard. While the parent compound 1 itself failed to show any significant antiviral activity against MV, its analogues containing hydrophobic substituents at the 2-position (2) or the 6-position (4) showed promising antiviral activity at submicromolar or micromolar concentration levels with no apparent toxicity to

  据报道，含有标题杂环系统的一类环膨胀（“脂肪”）核苷类似物（1-4）的合成和体外抗麻疹病毒（anti-MV）活性。通过适当取代的咪唑-1-核糖苷的4，5-二羧酸酯与适当取代的胍衍生物的碱催化缩合来合成目标化合物。以利巴韦林为对照标准，筛选化合物在非洲绿猴肾细胞（CV-1）中的抗MV活性。虽然母体化合物1本身未显示出对MV的任何重要抗病毒活性，其在2位（2）或6位（4）处含有疏水取代基的类似物在亚微摩尔或微摩尔浓度水平下显示出有希望的抗病毒活性，对宿主细胞系无明显毒性。两种化合物均显示出比对照药物利巴韦林更高的抗MV活性。
• Ring expanded nucleosides and nucleotides
  申请人：——

  公开号：US20040077564A1

  公开（公告）日：2004-04-22

  The present invention relates to compositions comprising analogues of purine nucleosides containing a ring-expanded (“fat”) heterocyclic ring, in place of purine, and an unmodified or modified sugar residue, pharmaceutically acceptable derivatives of such compositions, as well as methods of use thereof. In particular, these compositions may be utilized in the treatment of certain cancers, bacterial, fungal, parasitic, and viral infections, including, but not limited to, Acquired Immunodeficiency Syndrome (AIDS), hepatitis, Epstein-Barr and cytomegalovirus.

  本发明涉及含有环扩张（“肥胖”）杂环环代替嘌呤的嘌呤核苷类似物和未经改性或改性的糖残基的组合物，以及这些组合物的药学上可接受的衍生物，以及其使用方法。特别地，这些组合物可用于治疗某些癌症、细菌、真菌、寄生虫和病毒感染，包括但不限于获得性免疫缺陷综合症（AIDS）、肝炎、EB病毒和巨细胞病毒。
• Ring-expanded nucleosides and nucleotides
  申请人：Hosmane S. Ramachandra

  公开号：US20060241065A1

  公开（公告）日：2006-10-26

  The present invention relates to compositions comprising analogues of purine nucleosides containing a ring-expanded (“fat”) heterocyclic ring, in place of purine, and an unmodified or modified sugar residue, pharmaceutically acceptable derivatives of such compositions, as well as methods of use thereof. In particular, these compositions may be utilized in the treatment of certain cancers, bacterial, fungal, parasitic, and viral infections, including, but not limited to, Acquired Immunodeficiency Syndrome (AIDS), hepatitis, Epstein-Barr and cytomegalovirus.

  本发明涉及一种组成物，其包含嘌呤核苷类似物，其中嘌呤被扩展环（“fat”）杂环替代，并且含有未经修饰或修饰的糖残基，以及这种组成物的药学上可接受的衍生物，以及其使用方法。特别地，这些组成物可以用于治疗某些癌症、细菌、真菌、寄生虫和病毒感染，包括但不限于获得性免疫缺陷综合症（艾滋病）、肝炎、埃普斯坦-巴尔病毒和巨细胞病毒感染。
• An Efficient, Short Synthesis, and Potent Anti-Hepatitis B Viral Activity of a Novel Ring-Expanded Purine Nucleoside Analogue Containing a 5:7-Fused, Planar, Aromatic, Imidazo[4,5-<i>E</i>][1,3]diazepine Ring System
  作者：Huan-Ming Chen、Ramesh Sood、Ramachandra S. Hosmane

  DOI：10.1080/15257779908043079

  日期：1999.3

  An efficient, short synthesis of a ring-expanded nucleoside analogue containing a novel 5:7-fused, planar, and potentially aromatic imidazo[4,5-e][1,3]diazepine heterocyclic ring system is reported. The target compound, 6-amino-8-hydroxy-4H-1-beta-D- ribofuranosylimidazo[4,5-e][1,3]diazepin-4-one (2) was synthesized in a single step in > or = 90% yield by condensation of guanidine with either methyl

  高效，短环合成含有新型5：7融合，平面和潜在芳香族咪唑并[4,5-e] [1,3]二氮杂杂环体系的核苷类似物的报告。目标化合物6-氨基-8-羟基-4H-1-β-D-呋喃核糖嘧啶偶氮[4,5-e] [1,3]二氮杂-4--4-（2）一步合成通过胍与1-β-D-呋喃呋喃基嘧啶甲基-4,5-二羧酸甲酯（1a）或其2'，3'，5'-三-O-苯甲酰基衍生物（1b）的缩合得到= 90％的收率。化合物2在转染的肝癌细胞系2.2.15中显示出有效的抗乙型肝炎病毒（anti-HBV）活性，EC50值为0.17 microM，CC50值为2.4 mM的细胞毒性低（TI> 14,000）。
• US4115641A
  申请人：——

  公开号：US4115641A

  公开（公告）日：1978-09-19