β-L-5-iododioxolaneuracil

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: β-L-5-iododioxolaneuracil
• 英文别名: L-I-OddU；1-[(2S,4S)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]-5-iodopyrimidine-2,4-dione
• 化学式: C₈H₉IN₂O₅
• 分子量: 340.074
• InChiKey: GFRQBEMRUYIKAQ-WDSKDSINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  Benzoic acid (S)-4-(5-iodo-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-[1,3]dioxolan-2-ylmethyl ester 在 氨 作用下， 反应 24.0h， 生成 β-L-5-iododioxolaneuracil 、 (2S,4R)-1-<2-(hydroxymethyl)-1,3-dioxolan-4-yl>-5-iodouracil
  参考文献：
  名称：

  Structure−Activity Relationships of l-Dioxolane Uracil Nucleosides as Anti-Epstein Barr Virus Agents

  摘要：

  A series of 1,3-dioxolanyluracil analogues was prepared from the dioxolane intermediates 2, and their anti-Epstein Barr virus (anti-EBV) activities were detemined. The potency of L-dioxolane uracil nucleosides against EBV replication is dependent bn the substituents at the 5-position in the following decreasing order: I > Br > Cl > CH3 > CF3 > F. The most active and selective analogue was the iodo derivative (L-I-OddU) with an EC50 value of 0.03 mu M and an EC90 value of 0.16 mu M. There was no cytotoxicity or depletion of mitochondrial DNA in cells after exposure to L-I-OddU at 50 mu M. The action against EBV replication. in H1 cells is time-dependent, and EBV DNA in cells treated with L-I-OddU could rebound to pretreatment levels once the drug was removed. In view of the potent antiviral activity plus favorable toxicity profiles, L-I-OddU may be potentially useful for the treatment of EBV-related infectious diseases as well as for delaying the onset or decreasing the incidence of EBV-associated cancers.

  DOI：

  10.1021/jm9806749

文献信息

• Treatment of EBV and KHSV infection and associated abnormal cellular proliferation
  申请人：——

  公开号：US20030176392A1

  公开（公告）日：2003-09-18

  A method and composition for the treatment, prevention and/or prophylaxis of a host, and in particular, a human, infected with Epstein-Barr virus (EBV), is provided that includes administering an effective amount of a 5-substituted uracil nucleoside or its pharmaceutically acceptable salt or prodrug, optionally in a pharmaceutically acceptable diluent or excipient.

  提供了一种用于治疗、预防和/或预防寄主，特别是感染了爱泼斯坦-巴尔病毒（EBV）的人类的方法和组合物，包括向寄主施用有效量的5-取代尿嘧啶核苷或其药学上可接受的盐或前药，可选地还包括药学上可接受的稀释剂或赋形剂。
• MODIFIED FLUORINATED NUCLEOSIDE ANALOGUES
  申请人：CLARK JEREMY

  公开号：US20080070861A1

  公开（公告）日：2008-03-20

  The disclosed invention provides compositions and methods of treating a Flaviviridae infection, including hepatitis C virus, West Nile Virus, yellow fever virus, and a rhinovirus infection in a host, including animals, and especially humans, using a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleosides, or a pharmaceutically acceptable salt or prodrug thereof.

  本公开发明提供了用(2′R)-2′-脱氧-2′-氟-2′-C-甲基核苷或其药学上可接受的盐或前药治疗Flaviviridae感染的组合物和方法，包括丙型肝炎病毒、西尼罗病毒、黄热病毒和鼻病毒感染，在宿主中，包括动物，特别是人类。
• L-beta-dioxolane uridine analogs and methods for treating and preventing virus infections
  申请人：Yale University and The University of Georgia Research Foundation, Inc.

  公开号：US20010018440A1

  公开（公告）日：2001-08-30

  The present invention relates to the discovery that certain P-L-dioxolane nucleoside analogs which contain a uracil base, and preferably, a 5-halosubstituted uracil base, exhibit unexpectedly high activity against Epstein-Barr virus (EBV), Varciella-Zoster virus (VZV) and Herpes Virus 8 (HV-8). In particular, the compounds according to the present invention show potent inhibition of the replication of the virus (viral growth) in combination with very low toxicity to the host cells (i.e., animal or human tissue). Compounds are useful for treating EBV, VZV and HV-8 infections in humans.

  本发明涉及发现某些含有尿嘧啶碱基的P-L-二氧兰核苷类似物，尤其是含有5-卤代尿嘧啶碱基的类似物，对于Epstein-Barr病毒（EBV）、水痘带状疱疹病毒（VZV）和人类疱疹病毒8（HV-8）表现出意外的高活性。特别是，本发明的化合物在对宿主细胞（即动物或人体组织）的毒性非常低的情况下，显示出对病毒复制（病毒生长）的强效抑制。这些化合物对于治疗人类EBV、VZV和HV-8感染非常有用。
• Modified fluorinated nucleoside analogues
  申请人：Clark Jeremy

  公开号：US20050009737A1

  公开（公告）日：2005-01-13

  The disclosed invention provides compositions and methods of treating a Flaviviridae infection, including hepatitis C virus, West Nile Virus, yellow fever virus, and a rhinovirus infection in a host, including animals, and especially humans, using a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleosides, or a pharmaceutically acceptable salt or prodrug thereof.

  本公开发明提供了治疗黄热病病毒、西尼罗河病毒、肝炎C病毒、以及鼻病毒感染等黄病毒科感染的组合物和方法，包括对于动物和尤其是人类宿主，使用(2′R)-2′-脱氧-2′-氟-2′-C-甲基核苷或其药学上可接受的盐或前药。
• Treatment of EBV and KHSV Infection and Associated Abnormal Cellular Proliferation
  申请人：Schinazi Raymond F.

  公开号：US20100168052A1

  公开（公告）日：2010-07-01

  A method and composition for the treatment, prevention and/or prophylaxis of a host, and in particular, a human, infected with Epstein-Barr virus (EBV), is provided that includes administering an effective amount of a 5-substituted uracil nucleoside or its pharmaceutically acceptable salt or prodrug, optionally in a pharmaceutically acceptable diluent or excipient.

  本发明提供了一种用于治疗、预防和/或预防宿主，特别是人类，感染EB病毒（EBV）的方法和组合物，其中包括在药物接受者中给予有效量的5-取代尿嘧啶核苷或其药学上可接受的盐或前药，可选地在药学上可接受的稀释剂或赋形剂中。