5-bromo-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxylic acid methyl ester | 704911-41-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 三唑核糖核苷和核糖核苷酸
• 英文名称: 5-bromo-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxylic acid methyl ester
• 英文别名: methyl 5-bromo-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1,2,4-triazole-3-carboxylate；5-bromo-1-[2,3,5-tri-o-acetyl-β-D-ribofuranosyl]-1,2,4-triazole-3-carboxylate；methyl 5-bromo-1-[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(acetyloxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxylate
• CAS: 704911-41-1
• 化学式: C₁₅H₁₈BrN₃O₉
• 分子量: 464.227
• InChiKey: DQEJXBAFCDWDAT-PRULPYPASA-N

物化性质

• 沸点：
  563.7±60.0 °C(Predicted)
• 密度：
  1.73±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  145
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  5-bromo-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxylic acid methyl ester 在 氨 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以78%的产率得到5-bromo-1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide
  参考文献：
  名称：

  用于研究利巴韦林抗病毒作用机理的光标记探针的设计，合成和表征

  摘要：

  利巴韦林是迄今为止唯一可用于治疗丙型肝炎病毒感染的小分子，最近在紧急情况下用于治疗疾病早期的重症急性呼吸综合征（SARS）患者。为了研究通过使用光标记方法引起病毒唑抗病毒作用的机制，我们设计，合成并表征了叠氮三唑核苷1和2作为病毒唑的光标记探针。这些探针通过执行与NaN的相应的溴代三唑核苷的亲核取代中合成3（方案2），或通过与受保护的核糖的azidotriazole直接连结（方案4）。叠氮三唑核苷1和2显示出快速，清晰的光化学反应，这表明它们是用于光标记研究的有希望的候选者。

  DOI：

  10.1002/hlca.200490079
• 作为产物：
  描述：

  四乙酰核糖 、 5-溴-1,2,4-三唑-3-甲酸甲酯 在 PO(OH)(OC₆H₄NO₂)2 作用下， 反应 0.25h， 以45%的产率得到3-bromo-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-5-carboxylic acid methyl ester
  参考文献：
  名称：

  用于研究利巴韦林抗病毒作用机理的光标记探针的设计，合成和表征

  摘要：

  利巴韦林是迄今为止唯一可用于治疗丙型肝炎病毒感染的小分子，最近在紧急情况下用于治疗疾病早期的重症急性呼吸综合征（SARS）患者。为了研究通过使用光标记方法引起病毒唑抗病毒作用的机制，我们设计，合成并表征了叠氮三唑核苷1和2作为病毒唑的光标记探针。这些探针通过执行与NaN的相应的溴代三唑核苷的亲核取代中合成3（方案2），或通过与受保护的核糖的azidotriazole直接连结（方案4）。叠氮三唑核苷1和2显示出快速，清晰的光化学反应，这表明它们是用于光标记研究的有希望的候选者。

  DOI：

  10.1002/hlca.200490079

文献信息

• An Efficient Mixed-Ligand Pd Catalytic System to Promote CN Coupling for the Synthesis of N-Arylaminotriazole Nucleosides
  作者：Yuting Fan、Yi Xia、Jingjie Tang、Fabio Ziarelli、Fanqi Qu、Palma Rocchi、Juan L. Iovanna、Ling Peng

  DOI：10.1002/chem.201103918

  日期：2012.2.20

  Make it unique! A mixed‐ligand system of Pd/Synphos/Xantphos promotes effective CN coupling in the synthesis of various N‐arylaminotriazole and N‐arylaminopurine nucleoside analogues. This catalytic system is strikingly powerful and efficient, allowing for unparalleled substrate scope and high product yields as well as promotion of CCl bond activation for CN coupling (see scheme).

  使其独一无二！的Pd / Synphos /加入Xantphos的混合配体系统促进有效的C  N的各个的合成耦合Ñ -arylaminotriazole和Ñ -arylaminopurine核苷类似物。该催化体系是惊人地有力和有效的，从而允许无与伦比的底物范围和高的产物收率以及促进的C 对于C Cl键活化 N个耦合（参见方案）。
• Novel triazole nucleoside derivatives, their preparation and their application in therapeutics
  申请人：INSERM (Institut National de la Santé et de la Recherche Medicale)

  公开号：EP2113508A1

  公开（公告）日：2009-11-04

  The present invention relates to novel compound of formula (I): in the form of a free base or of an addition salt with an acid. The invention also relates to process of preparation of compounds of formula (I), to composition comprising them and to their application in therapeutics and in particular in cancers.

  本发明涉及一种新的化合物，其化学式为(I)，可以是自由碱或与酸形成的加成盐。本发明还涉及制备化合物(I)的方法，包括含有它们的组合物以及它们在治疗学中的应用，特别是在癌症治疗中的应用。
• Pd(dba)₂ vs Pd₂(dba)₃: An in-Depth Comparison of Catalytic Reactivity and Mechanism via Mixed-Ligand Promoted C–N and C–S Coupling Reactions
  作者：Mei Cong、Yuting Fan、Jean-Manuel Raimundo、Jingjie Tang、Ling Peng

  DOI：10.1021/ol501600k

  日期：2014.8.15

  With the help of mixed ligand catalytic systems, the analogous mechanisms behind the cognate performance by Pd(dba)2 and Pd2(dba)3 in catalyzing C-N and C-S coupling reactions were demonstrated. This information is instrumental in organic synthesis requiring Pd-catalyzed cross-coupling reactions and may also be valuable to other Pd-catalyzed transformations.
• Novel Triazole Ribonucleoside Down-Regulates Heat Shock Protein 27 and Induces Potent Anticancer Activity on Drug-Resistant Pancreatic Cancer
  作者：Yi Xia、Yang Liu、Jinqiao Wan、Menghua Wang、Palma Rocchi、Fanqi Qu、Juan L. Iovanna、Ling Peng

  DOI：10.1021/jm900960v

  日期：2009.10.8

  A series of novel 3-arylethynyltriazolyl ribonucleosides were synthesized and assessed for their anticancer activity on the drug-resistant pancreatic cancer cell line MiaPaCa-2. Among them, one compound exhibited potent apoptosis-inducing properties and anticancer activity against the pancreatic cancer model MiaPaCa-2 both in vitro and in vivo with no adverse effects. This compound did not inhibit DNA synthesis and therefore does not resemble the clinical drug gemcitabine. It did, however, significantly down-regulate the expression of heat shock protein 27 (Hsp27), a small molecular chaperone playing an important role in drug resistance and highly expressed in drug-resistant cancer forms, and thus represents the first small molecular anticancer lead with such a mode of action.
• Discovery of Novel Arylethynyltriazole Ribonucleosides with Selective and Effective Antiviral and Antiproliferative Activity
  作者：Jinqiao Wan、Yi Xia、Yang Liu、Menghua Wang、Palma Rocchi、Jianhua Yao、Fanqi Qu、Johan Neyts、Juan L. Iovanna、Ling Peng

  DOI：10.1021/jm800927r

  日期：2009.2.26

  Novel ethynyltriazole ribonucleosides were synthesized using a simple and efficient two-step procedure involving Sonogashira coupling and subsequent ammonolysis. Compounds 2f and 3o inhibited hepatitis C virus (HCV) replication efficiently, whereas compound 3f demonstrated potent apoptosis-induced antiproliferative activity against pancreatic cancer MiaPaCa-2 cells both in vitro and in vivo. Most interestingly, the notable selective antiviral and antiproliferative activities were achieved respectively for 2f and 3f by modulating the ribose sugar moiety into deprotected and protected forms while retaining a similar trifluoromethylphenylethynyltriazole as the nucleobase. Preliminary structure-activity relationship study revealed that not only the ribose moiety but also the CF3 group at the p-position of the phenyl ring and the rigid triple bond functionality contributed critically to the observed antiviral activity of 2f against HCV and antiproliferative activity of 3f against pancreatic cancer. These two compounds constitute therefore promising leads in the search for new antiviral and anticancer candidates.