1-[(2S,3S,4S,5S)-3,4-二羟基-5-(羟基甲基)四氢呋喃-2-基]-1,2,4-三唑-3-甲酰胺 | 206269-27-4

• 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
• 中文名称: 1-[(2S,3S,4S,5S)-3,4-二羟基-5-(羟基甲基)四氢呋喃-2-基]-1,2,4-三唑-3-甲酰胺
• 英文名称: ribavirin
• 英文别名: 1-β-L-ribofuranosyl-1,2,4-triazole-3-carboxamide；Levovirin；1-(β-L-ribofuranosyl)-1,2,4-triazole-3-carboxamide；Levovirin M；1-[(2S,3S,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide
• CAS: 206269-27-4
• 化学式: C₈H₁₂N₄O₅
• 分子量: 244.207
• InChiKey: IWUCXVSUMQZMFG-RGDLXGNYSA-N

物化性质

• 溶解度：
  DMSO（轻微）、甲醇（轻微、加热、超声处理）、水（轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[(2S,3S,4S,5S)-3,4-二羟基-5-(羟基甲基)四氢呋喃-2-基]-1,2,4-三唑-3-甲酰胺 在 吡啶 、 偶氮二异丁腈 、 triethylamine trihydrofluoride 、 二苯基硅烷 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 1-[(2S,4R,5S)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide
  参考文献：
  名称：

  Monocyclic l-Nucleosides with Type 1 Cytokine-Inducing Activity

  摘要：

  A series of 1,2,4-triazole L-nucleosides were synthesized and evaluated for their ability to stimulate type 1 cytokine production by activated human T cells in direct comparison to the known active agent ribavirin. Among the compounds prepared, 1-beta-L-ribofuranosyl-1,2,4-triazole-3-carboxamide (5, ICN 17261) was found to be the most uniformly potent compound. Conversion of the 3-carboxamide group of 5 to a carboxamidine functionality resulted in 1-beta-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride(10), which induced cytokine levels comparable to 5 for two of the three type 1 cytokines examined. Modification of the carbohydrate moiety of 5 provided compounds of reduced activity. Significantly, ICN 17261 offers interesting immunomodulatory potential for the treatment of diseases where type 1 cytokines play an important role.

  DOI：

  10.1021/jm9905514
• 作为产物：
  描述：

  L-呋喃核糖 在 盐酸 、 甲醇 、 双(对硝基苯基)磷酸酯 、 氨 作用下， 以 甲醇 为溶剂， 反应 59.42h， 生成 1-[(2S,3S,4S,5S)-3,4-二羟基-5-(羟基甲基)四氢呋喃-2-基]-1,2,4-三唑-3-甲酰胺
  参考文献：
  名称：

  Monocyclic l-Nucleosides with Type 1 Cytokine-Inducing Activity

  摘要：

  A series of 1,2,4-triazole L-nucleosides were synthesized and evaluated for their ability to stimulate type 1 cytokine production by activated human T cells in direct comparison to the known active agent ribavirin. Among the compounds prepared, 1-beta-L-ribofuranosyl-1,2,4-triazole-3-carboxamide (5, ICN 17261) was found to be the most uniformly potent compound. Conversion of the 3-carboxamide group of 5 to a carboxamidine functionality resulted in 1-beta-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride(10), which induced cytokine levels comparable to 5 for two of the three type 1 cytokines examined. Modification of the carbohydrate moiety of 5 provided compounds of reduced activity. Significantly, ICN 17261 offers interesting immunomodulatory potential for the treatment of diseases where type 1 cytokines play an important role.

  DOI：

  10.1021/jm9905514

文献信息

• Monocyclic L-Nucleosides, analogs and uses thereof
  申请人：ICN Pharmaceuticals, Inc.

  公开号：US06130326A1

  公开（公告）日：2000-10-10

  Novel monocyclic L-Nucleoside compounds have the general formula ##STR1## Embodiments of these compounds are contemplated to be useful in treating a wide variety of diseases including infections, infestations, neoplasms, and autoimmune diseases. Viewed in terms of mechanism, embodiments of the novel compounds show immunomodulatory activity, and are expected to be useful in modulating the cytokine pattern, including modulation of Th1 and Th2 response.

  新型单环L-核苷化合物的一般公式为##STR1##。这些化合物的实施形式被认为在治疗各种疾病方面是有用的，包括感染、寄生虫感染、肿瘤和自身免疫性疾病。从机制上看，这些新型化合物的实施形式显示出免疫调节活性，并有望在调节细胞因子模式方面发挥作用，包括调节Th1和Th2反应。
• Nucleotide mimics and their prodrugs
  申请人：——

  公开号：US20040059104A1

  公开（公告）日：2004-03-25

  The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

  本发明涉及核苷二磷酸模拟物和核苷三磷酸模拟物，其中包含二磷酸或三磷酸基团模拟物，以及可选的糖修饰和/或碱基修饰。本发明的核苷酸模拟物，以药学上可接受的盐、药学上可接受的前药或药物配方的形式，可用作抗病毒、抗微生物和抗癌剂。本发明提供了一种治疗病毒感染、微生物感染和增生性疾病的方法。本发明还涉及包含本发明化合物的药物组合物，可选地与其他药理活性剂结合。
• Antiviral nucleoside derivatives
  申请人：Roche Palo Alto LLC

  公开号：US20040121969A1

  公开（公告）日：2004-06-24

  The present invention relates to nucleosides of formula I wherein R 1 , R 2 and R 3 are as defined herein that modulateTh1 and Th2 immune activity, methods of using compounds according to formula I, alone or in combination therapy, for treatment of a bacterial or a viral infection, a parasite infestation, a cancer or tumor or an autoimmune disease and compositions containing prodrugs of the nucleoside of formula Ia. 1

  本发明涉及式I的核苷，其中R1、R2和R3如本文所定义，调节Th1和Th2免疫活性，使用符合式I的化合物的方法，单独或联合治疗细菌或病毒感染、寄生虫侵染、癌症或肿瘤或自身免疫疾病，并含有式Ia的核苷的前药的组合物。
• New Piperazine Compound and Use Thereof as a HCV Polymerase Inhibitor
  申请人：Abe Hiroyuki

  公开号：US20080081818A1

  公开（公告）日：2008-04-03

  The present invention relates to a compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof, or a solvate thereof and an anti-HCV agent and an HCV polymerase inhibitor containing this compound. The compound of the present invention shows an anti-HCV activity based on the HCV polymerase inhibitory activity, and useful as an agent for the prophylaxis or treatment of hepatitis C.

  本发明涉及一种由以下式[I]表示的化合物，其中每个符号如规范中定义，或其药学上可接受的盐，或其溶剂化合物，以及含有该化合物的抗HCV剂和HCV聚合酶抑制剂。本发明的化合物基于HCV聚合酶抑制活性显示出抗HCV活性，并且可用作预防或治疗丙型肝炎的药剂。
• Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation
  申请人：——

  公开号：US20030087873A1

  公开（公告）日：2003-05-08

  The disclosed invention is a composition for and a method of treating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction (“RT-PCR”). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.

  该公开的发明涉及一种用于治疗Flaviviridae（包括BVDV和HCV）、Orthomyxoviridae（包括甲型和乙型流感）或Paramyxoviridae（包括RSV）感染或与异常细胞增殖有关的病况的组合物和方法，适用于宿主，包括动物，尤其是人类，使用通用式（I）-（XXIII）的核苷或其药学上可接受的盐或前药。该发明还提供了一种有效的过程，用于量化病毒载量，特别是BVDV、HCV或西尼罗河病毒载量，使用实时聚合酶链反应（RT-PCR）。此外，该发明揭示了可以与样本中存在的病毒数量成比例发光的探针分子。