(2S,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2-ethynyl-5-(hydroxymethyl)tetrahydrofuran-3,4-diol | 1191237-75-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2-ethynyl-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
• 英文别名: (2S,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2-ethynyl-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 1191237-75-8
• 化学式: C₁₃H₁₄N₄O₄
• 分子量: 290.279
• InChiKey: AOBXNRJISYWUOA-VUXODMRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  瑞德西韦杂质7 、 (2S,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2-ethynyl-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 在 叔丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 反应 12.33h， 以21%的产率得到2-ethylbutyl ((((2R,3S,4R,5S)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate
  参考文献：
  名称：

  Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses

  摘要：

  The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC50 = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the l'-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model. Once-daily 10 mg/kg iv treatment on days 3-14 postinfection had a significant effect on viremia and mortality, resulting in 100% survival of infected treated animals [Nature 2016, 531, 381-385]. A phase 2 study (PREVAIL IV) is currently enrolling and will evaluate the effect of 4b on viral shedding from sanctuary sites in EBOV survivors.

  DOI：

  10.1021/acs.jmedchem.6b01594
• 作为产物：
  描述：

  瑞德西韦杂质1 在 三溴化硼 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 13.0h， 生成 (2S,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2-ethynyl-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 、 (2R,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2-ethynyl-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  [EN] METHODS AND COMPOUNDS FOR TREATING PARAMYXOVIRIDAE VIRUS INFECTIONS
  [FR] PROCÉDÉS ET COMPOSÉS POUR TRAITER DES INFECTIONS À VIRUS PARAMYXOVIRIDAE

  摘要：

  提供了一种治疗Paramyxoviridae病毒感染的方法，通过给予具有以下式（I）的核苷糖苷、核苷糖磷酸和其前药：其中核苷糖的1'位置被取代。所提供的化合物、组合物和方法特别适用于治疗人类副流感病毒和人类呼吸道合胞病毒感染。

  公开号：

  WO2012012776A1

文献信息

• METHODS FOR TREATING ARENAVIRIDAE AND CORONAVIRIDAE VIRUS INFECTIONS
  申请人：Gilead Sciences, Inc.

  公开号：US20170071964A1

  公开（公告）日：2017-03-16

  Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I: wherein the 1′ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.

  提供了通过给予核苷和其前药治疗Arenaviridae和Coronaviridae病毒感染的方法，其化学式为I： 其中核苷糖的1'位置被取代。所提供的化合物、组合物和方法特别适用于治疗拉沙病毒和胡宁病毒感染。
• Synthesis and antiviral activity of a series of 1′-substituted 4-aza-7,9-dideazaadenosine C-nucleosides
  作者：Aesop Cho、Oliver L. Saunders、Thomas Butler、Lijun Zhang、Jie Xu、Jennifer E. Vela、Joy Y. Feng、Adrian S. Ray、Choung U. Kim

  DOI：10.1016/j.bmcl.2012.02.105

  日期：2012.4

  A series of 1′-substituted analogs of 4-aza-7,9-dideazaadenosine C-nucleoside were prepared and evaluated for the potential as antiviral agents. These compounds showed a broad range of inhibitory activity against various RNA viruses. In particular, the whole cell potency against HCV when R = CN was attributed to inhibition of HCV NS5B polymerase and intracellular concentration of the corresponding

  制备了一系列 4-aza-7,9-dideazaadenosine C-核苷的 1'-取代类似物，并评估了其作为抗病毒剂的潜力。这些化合物对各种 RNA 病毒显示出广泛的抑制活性。特别是，当 R = CN 时，全细胞对 HCV 的效力归因于 HCV NS5B 聚合酶的抑制和相应核苷三磷酸的细胞内浓度。
• METHODS FOR THE PREPARATION OF RIBOSIDES
  申请人：Gilead Sciences, Inc.

  公开号：US20200197422A1

  公开（公告）日：2020-06-25

  Provided are methods of preparing compounds and pharmaceutical compositions for treating Filoviridae virus infections The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

  提供了用于治疗Filoviridae病毒感染的化合物和制药组合物的制备方法。所提供的化合物、组合物和方法特别适用于治疗马尔堡病毒、埃博拉病毒和库埃瓦病毒感染。
• 1' -substituted carba-nucleoside analogs for antiviral treatment
  申请人：GILEAD SCIENCES, INC.

  公开号：EP2937350A1

  公开（公告）日：2015-10-28

  Provided are pyrrolo[1,2-f][1,2,4]triazinyl, imidazo[1,5-f][1,2,4]triazinyl, imidazo[1,2-f][1,2,4]triazinyl, and [1,2,4]triazolo[4,3-f][1,2,4]triazinyl nucleosides, nucleoside phosphates and prodrugs thereof, wherein the 1' position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are useful for the treatment of Flaviviridae virus infections, particularly hepatitis C infections.

  本发明提供了吡咯并[1,2-f][1,2,4]三嗪基、咪唑并[1,5-f][1,2,4]三嗪基、咪唑并[1,2-f][1,2,4]三嗪基和[1,2,4]三唑并[4,3-f][1,2,4]三嗪基核苷、核苷磷酸酯及其原药，其中核苷糖的 1'位被取代。所提供的化合物、组合物和方法可用于治疗黄病毒科病毒感染，尤其是丙型肝炎感染。
• Methods for treating arenaviridae and coronaviridae virus infections
  申请人：Gilead Sciences, Inc.

  公开号：US10251904B2

  公开（公告）日：2019-04-09

  Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I: wherein the 1′ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.

  提供了通过施用式 I 的核苷及其原药治疗阿伦病毒科和冠状病毒科病毒感染的方法： 其中核苷糖的 1′位被取代。所提供的化合物、组合物和方法尤其适用于治疗拉沙病毒和朱宁病毒感染。