β-L-2'-deoxy-xylo-thimidine | 201295-39-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: β-L-2'-deoxy-xylo-thimidine
• 英文别名: L-xylo-dT；1-[4-Hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,3-dihydropyrimidine-2,4-dione；1-[(2S,4S,5S)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 201295-39-8
• 化学式: C₁₀H₁₄N₂O₅
• 分子量: 242.232
• InChiKey: IQFYYKKMVGJFEH-FXQIFTODSA-N

物化性质

• 密度：
  1.452±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◆ 母乳喂养期间使用概要：替比夫定已在美国市场停用。该药物尚未在正在接受乙型肝炎治疗的哺乳期母亲中进行研究。可能更倾向于使用其他药物，尤其是在哺乳新生儿或早产儿时。 对于乙型肝炎感染女性的婴儿，只要婴儿在出生时接受了乙型肝炎免疫球蛋白和乙型肝炎疫苗，母乳喂养和配方奶粉喂养的婴儿感染率没有差异。鼓励患有乙型肝炎的母亲在婴儿接受了这些预防措施后进行母乳喂养。 ◆ 对母乳喂养婴儿的影响：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:Telbivudine has been discontinued from the US market. It has not been studied in nursing mothers being treated for hepatitis B infection. An alternate drug may be preferred, especially while nursing a newborn or preterm infant. No difference exist in infection rates between breast-fed and formula-fed infants born to hepatitis B-infected women, as long as the infant receives hepatitis B immune globulin and hepatitis B vaccine at birth. Mothers with hepatitis B are encouraged to breastfeed their infants after their infants receive these preventative measures. ◉ 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：

  β-L-2'-deoxy-xylo-thimidine 在 吡啶 、 二苯基磷酸 、 溶剂黄146 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 生成 1-(3-azido-2,3-dideoxy-β-L-threo-pentofuranosyl)thymine
  参考文献：
  名称：

  New Unnatural L-Nucleoside Enantiomers:From Their Stereospecific Synthesis to Their Biological Activities

  摘要：

  Several purine and pyrimidine beta-L-dideoxynucleosides were stereospecifically synthesized and their antiviral properties examined. Two of them, namely beta-L-2', 3'-dideoxyadenosine (beta-L-ddA) and its 2',3'-didehydro derivative (beta-L-d4A) were found to have significant anti-human immunodeficiency virus (HIV) and anti-hepatitis B virus (HBV) activities in cell culture.

  DOI：

  10.1080/07328319708006190
• 作为产物：
  描述：

  O,O-二(三甲基甲硅烷基)胸苷 在 N-溴代丁二酰亚胺(NBS) 、 4 A molecular sieve 、 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.33h， 生成 β-L-2'-deoxy-xylo-thimidine
  参考文献：
  名称：

  Stereoselective Synthesis of 2'-Deoxy-.beta.-D-threo-pentofuranosyl Nucleosides by the NBS-Promoted Coupling Reaction of Thioglycosides with Silylated Heterocyclic Bases

  摘要：

  The NBS-promoted coupling reaction of phenyl 3,5-O-isopropylidene-2-deoxy-1-thio-alpha-D-threo-pentofuranoside (5e) with silylated pyrimidine bases was found to proceed in a highly stereoselective manner (alpha:beta = 1:24-0:1) to afford 2'-deoxy-beta-D-threo-pentofuranosyl pyrimidine nucleosides in satisfactory yields. The highly stereoselective outcome is thought to result from an in situ anomerization-type mechanism, in which intimate ionic intermediates would be in equilibrium and anomerize to the sterically preferable a form. A subsequent S(N)2 type attack to the intermediate will lead to the beta-nucleosides. By using this method, the synthesis of L-nucleosides, 1-(2-deoxy-beta-L-threo-pentofuranosyl)thymine and cytosine derivatives, was also demonstrated by starting from the L-enantiomer of the thioglycoside. On the other hand, the reaction with purine bases was accompanied by the production of undesirable N-7 regioisomers besides the desired N-9 products. The product distribution of the regioisomers was, however, proved to change with reaction time. For instance, a long reaction period allowed the thermodynamically stable N-9 isomers to be exclusively produced with moderate selectivity (alpha:beta = 1:2-1:4.8). The isolated yields of the 9-beta isomers after purification were acceptable for practical use.

  DOI：

  10.1021/jo00104a020

文献信息

• Bridged-Cyclo-ProTides as Prodrugs of Therapeutic Nucleosides and Nucleotides
  申请人：Zhong Minghong

  公开号：US20150266918A1

  公开（公告）日：2015-09-24

  Provided herein are bridged cyclic phosphates and phosphoramidates (bc-ProTides) of nucleosides, which is a compound, its stereoisomers, isotope-enriched analogues, pharmaceutically acceptable salts, hydrates, solvates, or crystalline or polymorphic forms thereof, with the following structure: These compounds can be used for the treatment of viral infections and/or neoplastic diseases in mammals. By optimizing combinations of Y 2 , Y 3 , R 0 , and M, the cleavability of these compounds as prodrugs can be attuned for different tissue targeting with various functional combinations. Also disclosed are processes and methods for preparation of these compounds.

  本文提供了核苷的桥接环磷酸酯和磷酰胺酯（bc-ProTides），这是一种化合物，包括其立体异构体、同位素富集类似物、药用可接受盐、水合物、溶剂合物，或其结晶或多形式，具有以下结构： 这些化合物可用于治疗哺乳动物的病毒感染和/或肿瘤性疾病。通过优化Y 2 、Y 3 、R 0 和M的组合，这些化合物作为前药的可裂性可以调节以适应不同组织靶向和各种功能组合。还公开了制备这些化合物的过程和方法。
• Beta-L-2'-Deoxy-Nucleosides for the Treatment of Hepatitis B
  申请人：Gosselin Gilles

  公开号：US20080188440A1

  公开（公告）日：2008-08-07

  This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2′-deoxy-β-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2′-deoxy-β-L-erythro-pentofuranonucleoside has the formula: wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted. The 2′-deoxy-β-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof may be administered either alone or in combination with another 2′-deoxy-β-L-erythro-pentofuranonucleoside or in combination with another anti-hepatitis B agent.

  该发明涉及一种治疗乙型肝炎感染宿主的方法，包括给予有效量的抗HBV生物活性2'-去氧-β-L-核糖核苷或其药学上可接受的盐或前药，其中2'-去氧-β-L-核糖核苷的化学式为：其中R选自H、直链、支链或环烷基、CO-烷基、CO-芳基、CO-烷氧基烷基、CO-芳氧基烷基、CO-取代芳基、烷基磺酰基、芳基磺酰基、芳基烷基磺酰基、氨基酸残基、单、二或三磷酸盐或磷酸衍生物；BASE是一种可以选择性地取代的嘌呤或嘧啶碱基。2'-去氧-β-L-核糖核苷或其药学上可接受的盐或前药可以单独或与另一种2'-去氧-β-L-核糖核苷或与另一种抗乙型肝炎药物联合使用。
• Compounds and pharmaceutical compositions for the treatment of viral infections
  申请人：Sommadossi Jean-Pierre

  公开号：US20080286230A1

  公开（公告）日：2008-11-20

  Provided herein are compounds, compositions and methods for the treatment of liver disorder, including HCV and/or HBV infections. Specifically, compound and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

  本文提供了用于治疗肝脏疾病，包括HCV和/或HBV感染的化合物、组合物和方法。具体地，本文公开了核苷衍生物的化合物和组合物，可以单独或与其他抗病毒药物联合使用。
• BETA-L-2' DEOXYNUCLEOSIDES FOR THE TREATMENT OF RESISTANT HBV STRAINS AND COMBINATION THERAPIES
  申请人：Standring David

  公开号：US20110172178A1

  公开（公告）日：2011-07-14

  It has been discovered that β-L-2′-deoxynucleosides are active against drug-resistant hepatitis B virus with mutations. A method for treating lamivudine resistant HBV (M552V) in a host is provided that includes administering a β-L-2′-deoxynucleoside or its pharmaceutically acceptable salt, ester or prodrug. In addition, a method for preventing lamivudine resistant HBV (M552V) mutation from occurring in a naïve host is provided that includes administering a β-L-2′-deoxynucleoside or its pharmaceutically acceptable salt, ester or prodrug. A method for preventing and/or suppressing the emergence of the HBV double mutant (L528M/M552V) in a host is also provided that includes administering a β-L-2′-deoxynucleoside or its pharmaceutically acceptable salt, ester or prodrug.

  已经发现β-L-2'-去氧核苷可以对具有突变的耐药性乙肝病毒发挥作用。提供了一种用于治疗宿主中拉米夫定耐药性乙肝病毒（M552V）的方法，包括给予β-L-2'-去氧核苷或其药学上可接受的盐、酯或前药。此外，还提供了一种用于预防拉米夫定耐药性乙肝病毒（M552V）突变在原始宿主中发生的方法，包括给予β-L-2'-去氧核苷或其药学上可接受的盐、酯或前药。还提供了一种用于预防和/或抑制宿主中HBV双突变体（L528M/M552V）出现的方法，包括给予β-L-2'-去氧核苷或其药学上可接受的盐、酯或前药。
• COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF VIRAL INFECTIONS
  申请人：SOMMADOSSI Jean-Pierre

  公开号：US20110286962A1

  公开（公告）日：2011-11-24

  Provided herein are compounds, compositions and methods for the treatment of liver disorder, including HCV and/or HBV infections. Specifically, compound and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

  本文提供了治疗肝脏疾病，包括HCV和/或HBV感染的化合物、组合物和方法。具体地，揭示了核苷衍生物的化合物和组合物，可以单独或与其他抗病毒药物联合使用。