(2R,3R,4R,5R)-5-Hydroxymethyl-3-methyl-2-purin-9-yl-tetrahydro-furan-3,4-diol

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (2R,3R,4R,5R)-5-Hydroxymethyl-3-methyl-2-purin-9-yl-tetrahydro-furan-3,4-diol
• 英文别名: (2R,3R,4R,5R)-5-(hydroxymethyl)-3-methyl-2-purin-9-yloxolane-3,4-diol
• 化学式: C₁₁H₁₄N₄O₄
• 分子量: 266.257
• InChiKey: HAUCHRMUNOHPHD-YJFSRANCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6-氯-9-(2-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 为溶剂， 以67%的产率得到(2R,3R,4R,5R)-5-Hydroxymethyl-3-methyl-2-purin-9-yl-tetrahydro-furan-3,4-diol
  参考文献：
  名称：

  嘌呤核糖核苷抑制丙型肝炎病毒 RNA 依赖性 RNA 聚合酶的构效关系。

  摘要：

  作为识别丙型肝炎病毒 (HCV) 复制抑制剂的持续努力的一部分，我们在此报告了一系列核苷类似物及其相应的三磷酸盐的合成和评估。评估了核苷在基于细胞的亚基因组复制子系统中抑制 HCV RNA 复制的能力，而评估了核苷三磷酸抑制由 HCV RNA 依赖性 RNA 聚合酶 NS5B 介导的体外 RNA 合成的能力。2'-C-甲基腺苷和 2'-C-甲基鸟苷被确定为 HCV RNA 复制的有效抑制剂，并且发现相应的三磷酸盐是 HCV NS5B 介导的 RNA 合成的有效抑制剂。在基于细胞的测定中产生的数据证明了围绕活性核苷的相当严格的构效关系。发现 C2 上超过甲基的空间体积增加、甲基取代基的立体化学或区域化学的变化，或杂碱的特性变化超过内源性腺嘌呤或鸟嘌呤的变化，会导致抑制活性的丧失。结果突出了核糖构型 2'-和 3'-羟基药效团在基于细胞的测定中抑制 HCV RNA 复制的重要性，并证明包含 2

  DOI：

  10.1021/jm030424e

文献信息

• Inhibiting Coronaviridae viral replication and treating Coronaviridae viral infection with nucleoside compounds
  申请人：——

  公开号：US20040259934A1

  公开（公告）日：2004-12-23

  Infection by a Coronaviridae virus (e.g., a coronavirus) and/or illness due to a Coronaviridae virus are treated or protected against by administration of a therapeutically or prophylactically effective amount of certain nucleoside compounds and derivatives thereof, either alone or in a composition comprising the nucleoside compound or its derivative and a pharmaceutically acceptable carrier. In addition, replication of a Coronaviridae virus is inhibited by administration of the nucleoside compounds and derivatives thereof, either alone or in pharmaceutical compositions. The nucleosides are particularly suitable for use in treating or prophylaxis of an infection by the SARS virus and/or in treating or prophylaxis of SARS, and for use in inhibiting replication of the SARS virus. The nucleoside compounds and derivatives can optionally be administered in combination with other agents active against the Coronaviridae virus and/or an illness due to the virus. The nucleoside compounds are also for use in the manufacture of medicaments for the inhibition of Coronaviridae virus replication, for the treatment or prophylaxis of Coronaviridae virus infection, and/or for the treatment or prophylaxis of an illness due to a Coronaviridae virus (e.g., the SARS virus). In addition, the compounds are for use as medicaments for the inhibition of Coronaviridae virus replication, for the treatment or prophylaxis of Coronaviridae virus infection, and/or for the treatment or prophylaxis of an illness due to a Coronaviridae virus.

  冠状病毒感染和/或由冠状病毒引起的疾病可通过给予某些核苷类化合物及其衍生物的治疗或预防有效剂量来治疗或防护，可以单独给予这些核苷类化合物或其衍生物，也可以与药用载体混合组成的组合物一起给予。此外，通过给予这些核苷类化合物及其衍生物，可以抑制冠状病毒的复制，可以单独给予或在药物组合中给予。这些核苷类化合物特别适用于用于治疗或预防SARS病毒感染和/或治疗或预防SARS，以及用于抑制SARS病毒的复制。这些核苷类化合物和其衍生物可以选择性地与其他对抗冠状病毒和/或由该病毒引起的疾病活性的药剂一起给予。这些核苷类化合物还可用于制造用于抑制冠状病毒复制、治疗或预防冠状病毒感染和/或治疗或预防冠状病毒引起的疾病（如SARS病毒）的药物。此外，这些化合物可用作用于抑制冠状病毒复制、治疗或预防冠状病毒感染和/或治疗或预防冠状病毒引起的疾病的药物。
• [EN] METHODS OF INHIBITING ORTHOPOXVIRUS REPLICATION WITH NUCLEOSIDE COMPOUNDS<br/>[FR] PROCEDE D'INHIBITION DE LA REPLICATION D'ORTHOPOXVIRUS AVEC DES COMPOSES DE NUCLEOSIDE
  申请人：MERCK & CO INC

  公开号：WO2003068244A1

  公开（公告）日：2003-08-21

  The present invention provides methods of inhibiting orthopoxvirus replication and/or treating orthopoxvirus infection with certain nucleoside compounds and derivatives thereof. These compounds are particularly useful as inhibitors of vaccinia virus and variola virus replication and/or for the treatment of vaccinia virus and variola virus infection. The nucleoside compounds may be administered alone or in combination with other agents active against orthopoxvirus infection, in particular against vaccinia virus or variola virus infection. Another aspect of the present invention provides for the use of such nucleoside compounds in the manufacture of a medicament for the inhibition of orthopoxvirus replication and/or for the treatment of orthopoxvirus infection. Yet a further aspect of the present invention provides such nucleoside compounds for use as a medicament for the inhibition of orthopoxvirus replication and/or for the treatment of orthopoxvirus infection.

  本发明提供了使用某些核苷类化合物及其衍生物抑制正痘病毒复制和/或治疗正痘病毒感染的方法。这些化合物特别适用于抑制天花病毒和痘病毒的复制和/或治疗天花病毒和痘病毒感染。这些核苷类化合物可以单独或与其他对抗正痘病毒感染的药物联合使用，特别是对抗天花病毒或痘病毒感染的药物。本发明的另一个方面提供了将这些核苷类化合物用于制造药物，以抑制正痘病毒复制和/或治疗正痘病毒感染。本发明的另一个方面提供了这些核苷类化合物作为药物，以抑制正痘病毒复制和/或治疗正痘病毒感染。
• Methods of inhibiting orthopoxvirus replication with nucleoside compounds
  申请人：Olsen B. David

  公开号：US20050164960A1

  公开（公告）日：2005-07-28

  The present invention provides methods of inhibiting orthopoxvirus replication and/or treating orthopoxvirus infection with certain nucleoside compounds and derivatives thereof. These compounds are particularly useful as inhibitors of vaccinia virus and variola virus replication and/or for the treatment of vaccinia virus and variola virus infection. The nucleoside compounds may be administered alone or in combination with other agents active against orthopoxvirus infection, in particular against vaccinia virus or variola virus infection. Another aspect of the present invention provides for the use of such nucleoside compounds in the manufacture of a medicament for the inhibition of orthopoxvirus replication and/or for the treatment of orthopoxvirus infection. Yet a further aspect of the present invention provides such nucleoside compounds for use as a medicament for the inhibition of orthopoxvirus replication and/or for the treatment of orthopoxvirus infection.

  本发明提供了使用某些核苷类化合物及其衍生物来抑制正痘病毒复制和/或治疗正痘病毒感染的方法。这些化合物特别适用于抑制天花病毒和痘病毒的复制和/或治疗天花病毒和痘病毒感染。这些核苷类化合物可以单独或与其他对抗正痘病毒感染的药物联合使用，特别是对抗天花病毒或痘病毒感染的药物。本发明的另一方面提供了将这些核苷类化合物用于制造用于抑制正痘病毒复制和/或治疗正痘病毒感染的药物。本发明的另一个方面提供了这些核苷类化合物作为用于抑制正痘病毒复制和/或治疗正痘病毒感染的药物。
• Inhibiting orthopoxvirus replication with nucleoside compounds
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1476169B1

  公开（公告）日：2013-03-20
• EP1476169A4
  申请人：——

  公开号：EP1476169A4

  公开（公告）日：2009-06-03