1-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide | 1192243-01-8

• 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: 1-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide
• 英文别名: 1-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide
• CAS: 1192243-01-8
• 化学式: C₈H₁₂N₄O₅
• mdl: MFCD01544655
• 分子量: 244.2
• InChiKey: IWUCXVSUMQZMFG-UHFFFAOYSA-N

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：
  0.625
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  7

ADMET

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用总结：利巴韦林尚未在正在接受丙型肝炎治疗的哺乳期母亲中进行研究。然而，利巴韦林通过吸入方式直接给予婴儿以治疗呼吸道合胞病毒（RSV）感染。乳汁中的量可能低于接受利巴韦林治疗的RSV感染婴儿的剂量。 丙型肝炎不会通过母乳传播，母乳已被证明可以灭活丙型肝炎病毒（HCV）。然而，疾病控制中心建议，如果感染HCV的母亲乳头裂开或出血，应考虑停止哺乳。目前尚不清楚这一警告是否适用于正在接受丙型肝炎治疗的母亲。 出生时母亲患有HCV感染的婴儿应进行HCV感染检测；因为母体抗体在生命的前18个月内存在，并且在婴儿产生免疫反应之前，推荐进行核酸检测。 对哺乳婴儿的影响：截至修订日期，未找到相关的已发布信息。 对哺乳和母乳的影响：截至修订日期，未找到相关的已发布信息。

◉ Summary of Use during Lactation:Ribavirin has not been studied in nursing mothers being treated for hepatitis C infection. However, ribavirin is given directly to infants by inhalation to treat respiratory syncytial virus (RSV) infection. The amount in milk is likely to be lower than the doses received by infants treated with ribavirin for RSV infection. Hepatitis C is not transmitted through breastmilk and breastmilk has been shown to inactivate hepatitis C virus (HCV). However, the Centers for Disease Control recommends that mothers with HCV infection should consider abstaining from breastfeeding if their nipples are cracked or bleeding. It is not clear if this warning would apply to mothers who are being treated for hepatitis C. Infants born to mothers with HCV infection should be tested for HCV infection; because maternal antibody is present for the first 18 months of life and before the infant mounts an immunologic response, nucleic acid testing is recommended. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为反应物：
  描述：

  1-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide 生成 三氮唑核苷 2',3',5'-三乙酸酯
  参考文献：
  名称：

  1,2,4-triazole nucleosides

  摘要：

  制备了在3号位置取代且具有公式I的Ac和Y具有声明中所述含义的1-(O-酰基阻断-ss-D-核糖呋喃基)-1,2,4-三唑。方法是将相应的三唑与相应的核糖呋喃衍生物反应。根据本发明，可以通过水解从公式I的化合物中消除酰基基团。水解产物反过来可以用来制备具有公式V的相应磷酸化合物，其中Y具有与公式I相同的含义，并且至少一个Z基团具有磷酸酰基的酰基含义，而另一个Z基团则同样具有磷酸酰基的酰基含义或者是氢原子。然后将水解产物酯化以给出公式V的磷酸酯。公式I的化合物以及由其水解得到的1-(ss-D-核糖呋喃基)-1,2,4-三唑-3-羧酰胺核苷具有相当的抗病毒活性和抗肿瘤活性。

  公开号：

  US03798209A1
• 作为产物：
  描述：

  三乙酰利巴韦林甲酯 以96.7的产率得到1-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide
  参考文献：
  名称：

  一种利巴韦林的制备方法

  摘要：

  本发明公开了一种利巴韦林的制备方法，步骤为：A、以肌苷为原料，加入酸和催化剂I进行酰化反应，生成四乙酰核糖；B、将步骤A的四乙酰核糖和1，2，4-三氮唑-3-羧酸甲酯分别先用活性炭处理后，再将四乙酰核糖和1，2，4-三氮唑-3-羧酸甲酯混合均匀，然后加入催化剂II进行缩合反应得缩合物；C、将步骤B的缩合物在氨和甲醇中氨解生产出利巴韦林粗品；D、将步骤C的利巴韦林粗品进行精制处理得利巴韦林纯品。该方法操作简单、选择性好、清洁环保、利巴韦林收率高。

  公开号：

  CN102286046A

文献信息

• Process for preparing 1,2,4-triazole nucleosides
  申请人：ICN Pharmaceuticals, Inc.

  公开号：US04138547A1

  公开（公告）日：1979-02-06

  1-.beta.-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide is prepared by a process wherein a suitably substituted formimidic acid hydrazide is condensed with a blocked derivative of D-ribose and the intermediate is ring closed with a reagent which donates one carbon atom to yield a 3-substituted-1-(blocked .beta.-D-ribofuranosyl)-1,2,4-triazole. Treatment of this intermediate with ammonia and/or removal of the blocking group yields the product.

  1-.beta.-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide是通过以下过程制备的：将适当取代的甲酰胺肼与D-核糖的阻断衍生物缩合，中间体经过环合反应，其中一个碳原子由试剂提供，形成3-取代-1-(阻断的β-D-核糖呋喃基)-1,2,4-三唑。将该中间体与氨和/或去除阻断基即可得到产物。
• Active agent delivery systems and methods for protecting and administering active agents
  申请人：Mickle Travis

  公开号：US20070232529A1

  公开（公告）日：2007-10-04

  The present invention relates to active agent delivery systems and more specifically to compositions that comprise amino acids, as single amino acids or peptides, covalently attached to active agents and methods for administering conjugated active agent compositions.

  本发明涉及活性物质输送系统，更具体地涉及包含氨基酸（作为单个氨基酸或肽）与活性物质共价连接的组合物以及用于给予共轭活性物质组合物的方法。
• ACTIVE AGENT DELIVERY SYSTEMS AND METHODS FOR PROTECTING AND ADMINISTERING ACTIVE AGENTS
  申请人：Mickle Travis

  公开号：US20090253792A1

  公开（公告）日：2009-10-08

  The present invention relates to active agent delivery systems and more specifically to compositions that comprise amino acids, as single amino acids or peptides, covalently attached to active agents and methods for administering conjugated active agent compositions.

  本发明涉及活性剂递送系统，更具体地涉及包含氨基酸（作为单个氨基酸或肽）与活性剂共价连接的组合物以及给予共轭活性剂组合物的方法。
• MACROCYCLIC COMPOUNDS AS INHIBITORS OF VIRAL REPLICATION
  申请人：BLATT LAWRENCE M.

  公开号：US20090286843A1

  公开（公告）日：2009-11-19

  The embodiments provide compounds of the general formulas I-XIX, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating flaviviral infection, including hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

  该实施例提供了一般式I-XIX的化合物，以及包括药物组合物在内的组合物。该实施例还提供了治疗方法，包括治疗黄热病毒感染的方法，包括丙型肝炎病毒感染的方法和治疗肝纤维化的方法，通常涉及向需要治疗的个体施用所述化合物或组合物的有效量。
• ACTIVE AGENT DELIVERY SYSTEMS AND METHODS FOR PROTECTING AND ADMINISTERING ACTIVE AGENTS
  申请人：Mickle Travis

  公开号：US20090306228A1

  公开（公告）日：2009-12-10

  The present invention relates to active agent delivery systems and more specifically to compositions that comprise amino acids, as single amino acids or peptides, covalently attached to active agents and methods for administering conjugated active agent compositions.

  本发明涉及活性剂递送系统，更具体地涉及包含氨基酸，作为单个氨基酸或肽，与活性剂共价结合的组合物以及用于给予共轭活性剂组合物的方法。