3-azido-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-5-carboxylic acid methyl ester | 704911-46-6

• 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: 3-azido-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-5-carboxylic acid methyl ester
• 英文别名: methyl 3-azido-1-[2,3,5-tri-O-acetyl-β-D-ribofuranosyl]-1,2,4-triazole-5-carboxylate；methyl 5-azido-2-[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(acetyloxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxylate
• CAS: 704911-46-6
• 化学式: C₁₅H₁₈N₆O₉
• 分子量: 426.343
• InChiKey: HFVOEQMOODNMFE-PRULPYPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  160
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  3-azido-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-5-carboxylic acid methyl ester 在 5% Pd(II)/C(eggshell) 、 氢气 作用下， 以 二氯甲烷 为溶剂， 以98%的产率得到(2R,3R,4R,5R)-2-(acetoxymethyl)-5-(3-amino-5-(methoxycarbonyl)-1H-1,2,4-triazol-1-yl)tetrahydrofuran-3,4-diyl diacetate
  参考文献：
  名称：

  N-Aryltriazole ribonucleosides with potent antiproliferative activity against drug-resistant pancreatic cancer

  摘要：

  Novel N-aryltriazole nucleosides were synthesized via Cu-mediated C-N cross-coupling reaction starting with 3-aminotriazole ribonucleoside and various boronic acids. Two of them exhibited potent apoptosis-related antiproliferative activity against the drug-resistant pancreatic cancer cell line MiaPaCa-2, with an increased potency compared to gemcitabine, the reference treatment for pancreatic cancer. A preliminary SAR study suggests that the appended N-aryl moiety and the substituent at its para-position, as well as the ribose sugar component, contribute considerably to the observed antiproliferative activity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.104
• 作为产物：
  描述：

  四乙酰核糖 、 3-叠氮基-5-甲氧羰基-1,2,4-三唑 在 PO(OH)(OC₆H₄NO₂)2 作用下， 反应 0.25h， 以66%的产率得到3-azido-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

• Synthesis of bitriazolyl nucleosides and unexpectedly different reactivity of azidotriazole nucleoside isomers in the Huisgen reaction
  作者：Yi Xia、Wei Li、Fanqi Qu、Zhijin Fan、Xiufeng Liu、Charles Berro、Evelyne Rauzy、Ling Peng

  DOI：10.1039/b703420b

  日期：——

  Novel bitriazolyl nucleosides were synthesized via the Huisgen reaction, starting with 3-azidotriazole nucleoside (1). Surprisingly, its isomer, 5-azidotriazole nucleoside (1′) did not yield the corresponding Huisgen reaction products efficiently because it was rapidly reduced to amine in the presence of Cu(II)–ascorbate. The significant differences between the reactivity of these two isomers in Cu(II)–ascorbate mediated reactions are mainly due to differences in their electronic properties and steric congestion as a result of different relative positions of the azido and the ribosyl moieties.

  新型双氮核苷通过Huisgen反应合成，起始材料为3-叠氮三唑核苷（1）。令人惊讶的是，其异构体5-叠氮三唑核苷（1′）在Cu(II)－抗坏血酸的存在下，并未有效生成相应的Huisgen反应产物，因为它迅速被还原为胺。这两种异构体在Cu(II)－抗坏血酸介导反应中的反应活性显著差异，主要是由于它们的电子性质和空间拥挤度的不同，这些差异源于叠氮基与核糖基的相对位置不同。
• PHOTOLABELING PROBES OF RIBAVIRIN AND EICAR
  作者：Qiongyou Wu、Fanqi Qu、Jinqiao Wan、Yi Xia、Ling Peng

  DOI：10.1081/ncn-200060336

  日期：2005.4.1

  order to study the mechanisms responsible for their antiviral effects using a photolabeling approach, we have developed photolabeling probes of ribavirin and EICAR, in which an azido group was introduced into the pseudobases of triazole and imidazole, respectively. The ribavirin photoprobes were obtained by directly coupling the azidotriazole to the protected ribose sugar, while the EICAR probe was prepared

  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严重急性呼吸系统综合症患者。EICAR 是利巴韦林最有效的同系物之一，其抗病毒效力是利巴韦林的 10 到 100 倍。利巴韦林和 EICAR 抗病毒作用的潜在机制尚未明确阐明，但它们似乎相似。为了使用光标记方法研究其抗病毒作用的机制，我们开发了利巴韦林和 EICAR 的光标记探针，其中将叠氮基分别引入三唑和咪唑的假碱基中。利巴韦林光探针是通过将叠氮三唑直接偶联到受保护的核糖上而获得的，而 EICAR 探针是通过重氮化 AICAR 并随后用 NaN3 取代来制备的。所有这些探针都显示出快速、清晰的光化学反应，这表明它们是用于光标记研究的有前途的工具。
• 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.