(2S,4S)-1-<2-(hydroxymethyl)-1,3-dioxolan-4-yl>-5-chlorouracil

• 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: (2S,4S)-1-<2-(hydroxymethyl)-1,3-dioxolan-4-yl>-5-chlorouracil
• 英文别名: 5-chloro-1-[(2S,4S)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]pyrimidine-2,4-dione
• 化学式: C₈H₉ClN₂O₅
• 分子量: 248.623
• InChiKey: DCPCHBMAICQGGJ-WDSKDSINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 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：

  [(2S)-4-(5-chloro-2,4-dioxopyrimidin-1-yl)-1,3-dioxolan-2-yl]methyl benzoate 在 氨 作用下， 反应 24.0h， 生成 (2S,4S)-1-<2-(hydroxymethyl)-1,3-dioxolan-4-yl>-5-chlorouracil 、 (2S,4R)-1-<2-(hydroxymethyl)-1,3-dioxolan-4-yl>-5-chlorouracil
  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

• 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。
• L-$g(b)-DIOXOLANE URIDINE ANALOGS AND METHODS FOR TREATING AND PREVENTING VIRUS INFECTIONS
  申请人：YALE UNIVERSITY

  公开号：EP0956021A1

  公开（公告）日：1999-11-17
• L-BETA-DIOXOLANE URIDINE ANALOGS FOR TREATING AND PREVENTING INFECTIONS BY EBV, VZV AND HV-8
  申请人：YALE UNIVERSITY

  公开号：EP0956021B1

  公开（公告）日：2004-11-03
• US6274589B1
  申请人：——

  公开号：US6274589B1

  公开（公告）日：2001-08-14
• [EN] L- beta -DIOXOLANE URIDINE ANALOGS AND METHODS FOR TREATING AND PREVENTING VIRUS INFECTIONS<br/>[FR] ANALOGUES DE L- DOLLAR (b)-DIOXOLANE URIDINE ET METHODES DE PREVENTION ET DE TRAITEMENT D'INFECTIONS VIRALES
  申请人：YALE UNIVERSITY

  公开号：WO1998020879A1

  公开（公告）日：1998-05-22

  (EN) The present invention relates to the discovery that certain $g(b)-L-dioxolane nucleoside analogs which contain a uracil base, and preferably, a 5-halosubstituted uracil base, exhibit unexpectedly high activity against Epstein-Barr virus (EBV), Varicella-Zoster virus (VZV) and Human Herpes Virus 8 (HV-8). In particular, the compounds according to the present invention show potent inhibition of the replication of the virus (viral growth) in combination with very low toxicity to the host cells (i.e., animal or human tissue). Compounds are useful for treating EBV, VZV and HV-8 infections in humans.(FR) La présente invention concerne la découverte selon laquelle certains analogues de nucléosides de L-$g(b)-dioxolane contenant une base uracile, et de préférence, une base uracile 5-halogénosubstituée, présentent une activité élevée inattendue contre le virus Eptsein-Barr, l'herpèsvirus varicellae et le virus de l'herpès humain 8. Les composés de l'invention présente notamment une forte inhibition de la réplication du virus (croissance du virus) et une toxicité très faible vis-à-vis des cellules hôtes (c'est-à-dire, des tissus animaux ou humains). Ces composés sont utiles pour traiter le virus Epstein-Barr, l'herpèsvirus varicellae et les infection dues à l'herpèsvirus 8 chez les humains.