1-[(2R,4S,5R)-5-(羟基甲基)-4-甲氧基四氢呋喃-2-基]-5-甲基嘧啶-2,4-二酮 | 108895-42-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 1-[(2R,4S,5R)-5-(羟基甲基)-4-甲氧基四氢呋喃-2-基]-5-甲基嘧啶-2,4-二酮
• 中文别名: 3-苯并呋喃丙酸,a-氨基-
• 英文名称: 3'-O-methylthymidine
• 英文别名: 1-[(2R,4S,5R)-5-(hydroxymethyl)-4-methoxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 108895-42-7
• 化学式: C₁₁H₁₆N₂O₅
• 分子量: 256.258
• InChiKey: ZGBKEOLAPVBJFC-DJLDLDEBSA-N

物化性质

• 溶解度：
  溶于氯仿、二氯甲烷、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[(2R,4S,5R)-5-(羟基甲基)-4-甲氧基四氢呋喃-2-基]-5-甲基嘧啶-2,4-二酮 在 碘代三甲硅烷 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 65.5h， 生成 [(2R,3S,5R)-5-(4-Hydroxy-5-methyl-2-oxo-2H-pyrimidin-1-yl)-3-methoxy-tetrahydro-furan-2-ylmethoxymethyl]-phosphonic acid
  参考文献：
  名称：

  5′-O-膦酰基甲基-2′，3′-二脱氧核苷：合成和抗HIV活性。

  摘要：

  通过在氢化钠存在下使后者与[（对甲苯磺酰基）氧基]甲膦酸二乙酯（1）反应，实现不同嘧啶2'，3'-二脱氧核苷的5'-O-膦酰基甲基化。通过1H和13C NMR和MS分析可以轻松地区分碱基膦酰基甲基化（15-19）和糖膦酰基甲基化（8-12）衍生物。用N3-苯甲酰基保护尿嘧啶或胸腺嘧啶残基不能阻止碱基修饰。然而，O4-甲基保护的2'，3'-二脱氧尿苷容易得到5'-O-膦酰基甲基化的衍生物12，该衍生物被转化为2'，3'-二脱氧尿苷类似物27和2'，3'-二脱氧胞苷。对应物29. 3'-脱氧胸苷（23），2'，3'-二脱氧尿苷，（27），2'，3'的5'-O-膦酰基甲基衍生物 -二脱氧胞苷（29），3'-O-甲基胸苷（26）和3'-氨基-3'-脱氧胸苷（28）在MT-4细胞中未显示出明显的抗HIV活性。相反，3'-脱氧-3'-氟胸苷（24）和3'-叠氮基3'-脱氧胸苷（25）的5'-O-膦酰基

  DOI：

  10.1021/jm00171a023
• 作为产物：
  描述：

  3'-O-<<<2-(methylthio)phenyl>thio>methyl>thymidine 在 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 甲苯 为溶剂， 反应 2.5h， 以73%的产率得到1-[(2R,4S,5R)-5-(羟基甲基)-4-甲氧基四氢呋喃-2-基]-5-甲基嘧啶-2,4-二酮
  参考文献：
  名称：

  [[2-(Methylthio)phenyl]thio]methyl (MTPM): a new protecting group of hydroxyl groups capable of conversion to a methyl group

  摘要：

  DOI：

  10.1021/jo00286a041

文献信息

• 3'-or 2'-hydroxymethyl substituted nucleoside derivatives for treatment of hepatites virus infections
  申请人：——

  公开号：US20020055483A1

  公开（公告）日：2002-05-09

  The present invention relates to a composition for and a method of treating hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, hepatitis D virus (HDV) infection or a proliferative disorder in a patient using an effective amount of a compound selected from the group consisting of formulas [I]- [IV] below and mixtures of two or more thereof: 1 wherein the substituents are as defined herein. Pharmaceutical compositions comprising these compounds in combination with other HBV, HCV, or HDV agents is also disclosed.

  本发明涉及一种用于治疗患有乙型肝炎病毒（HBV）感染、丙型肝炎病毒（HCV）感染、丁型肝炎病毒（HDV）感染或患有增生性疾病的患者的组合物和方法，所述方法使用从下面的公式I-IV中选择的化合物或两个或两个以上化合物的混合物的有效量：其中，取代基如本文所定义。还公开了包含这些化合物与其他HBV、HCV或HDV药物组合的制药组合物。
• 3'-Substituted methyl nucleosides as antiviral agents
  申请人：Bristol-Myers Squibb Company

  公开号：EP0391411A2

  公开（公告）日：1990-10-10

  Certain 3′-substituted methyl nucleosides are disclosed which are useful in the treatment of viral infections, e.g., infections caused by herpes simplex virus types 1 and 2, and/or are useful as intermediates in the preparation of 3′-substituted methyl nucleosides having antiviral activity. In accordance with one aspect of the invention, there are provided novel 3′-substituted methyl nucleosides represented by Formulas I and II wherein: B indicates that B can be either alpha or beta; B is a member selected from the group consisting of the pyrimidine and purine nucleoside bases connected to the tetrahydrofuran ring through the N¹ heterocyclic nitrogen atom of the pyrimidines and the N⁹ or N⁷ heterocyclic nitrogen atom of the purines including the naturally occurring nucleoside bases and 5-fluoro, 5-bromo, 5-iodo, 5-chloro, 5-trifluoromethyl, 5-ethyl, 5-(2-bromovinyl)­uracil; triazolecarboxamide; 2-aminopurine; 2,6-diaminopurine; 4-chloropyrimidine; pyrimidine; azapyrimidine; purine; 2,6-dichloropurine; 2-amino-6-­chloropurine; and deazapurine; R and Q are either both hydrogen or halogen, especially fluorine, or one is hydrogen and the other one is hydroxy or halogen, especially fluorine; in Formula I at least one of R and Q is halogen; and X and Y can be the same or different and are selected from the group consisting of O-alkyl, O-aryl, O-acyl-, halogen, especially fluorine, azido, amino, acylamido, -SH, S-alkyl and S-aryl, or one of X or Y can be hydroxy, or X may be the group R¹O and Y may be the group R²O wherein R¹ and R² are hydrogen or hydroxy-protecting groups. Preferred O-alkyl and S-alkyl groups contain from one to four carbon atoms; preferred O-aryl and S-aryl groups contain from 6 to 10 carbon atoms; and preferred O-acyl groups contain from one to four carbon atoms.

  本发明公开了某些3′-取代的甲基核苷，它们可用于治疗病毒感染，例如由单纯疱疹病毒1型和2型引起的感染，和/或可用作制备具有抗病毒活性的3′-取代的甲基核苷的中间体。根据本发明的一个方面，提供了由式 I 和 II 表示的新型 3′-取代的甲基核苷 其中 B表示B可以是α或β； B 是选自以下组成的组的成员：通过嘧啶的 N¹ 杂环氮原子和嘌呤的 N⁹ 或 N⁷ 杂环氮原子与四氢呋喃环连接的嘧啶和嘌呤核苷碱基，包括天然存在的核苷碱基和 5-氟、5-溴、5-碘、5-氯、5-三氟甲基、5-乙基、5-(2-溴乙烯基)尿嘧啶；三唑甲酰胺； 2-氨基嘌呤； 2,6-二氨基嘌呤；4-氯嘧啶；嘧啶；氮杂嘧啶；嘌呤；2,6-二氯嘌呤；2-氨基-6-氯嘌呤；以及去氮嘌呤； R 和 Q 要么都是氢或卤素，特别是氟，要么一个是氢，另一个是羟基或卤素，特别是氟；在式 I 中，R 和 Q 中至少有一个是卤素；以及 X 和 Y 可以相同或不同，选自由 O-烷基、O-芳基、O-酰基、卤素（尤其是氟）、叠氮、氨基、酰氨基、-SH、S-烷基和 S-芳基组成的组，或者 X 或 Y 中的一个可以是羟基，或者 X 可以是基团 R¹O，Y 可以是基团 R²O，其中 R¹ 和 R² 是氢或羟基保护基团。 优选的 O-烷基和 S-烷基含有 1 至 4 个碳原子；优选的 O-芳基和 S-芳基含有 6 至 10 个碳原子；优选的 O-酰基含有 1 至 4 个碳原子。
• 3'-or 2'-hydroxymethyl substituted nucleoside derivatives for treatment of viral infections
  申请人：Pharmasset, Inc.

  公开号：EP1964569A2

  公开（公告）日：2008-09-03

  The present invention relates to a composition for and a method of treating hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, hepatitis D virus (HDV) infection or a proliferative disorder in a patient using an effective amount of a compound selected from the group consisting of formulas (I)-(IV) below and mixtures of two or more thereof, wherein the substituents are as defined herein. Pharmaceutical compositions comprising these compounds in combination with other HBV, HCV, or HDV agents is also disclosed.

  本发明涉及一种治疗乙型肝炎病毒（HBV）感染、丙型肝炎病毒（HCV）感染、丁型肝炎病毒（HDV）感染或患者增殖性疾病的组合物和方法，使用有效量的选自下式（I）-（IV）组成的组的化合物及其两种或两种以上的混合物，其中取代基如本文所定义。还公开了由这些化合物与其他 HBV、HCV 或 HDV 制剂组合而成的药物组合物。
• Linkers and co-coupling agents for optimization of oligonucleotide synthesis and purification on solid support
  申请人：The Regents of the University of Michigan

  公开号：EP2048149A2

  公开（公告）日：2009-04-15

  A method of modulation of synthesis capacity on and cleavage properties of synthetic oligomers from solid support is described. The method utilizes linker molecules attached to a solid surface and co-coupling agents that have similar reactivities to the coupling compounds with the surface functional groups. The preferred linker molecules provide an increased density of polymers and more resistance to cleavage from the support surface. The method is particularly useful for synthesis of oligonucleotides, oligonucleotides microarrays, peptides, and peptide microarrays. The stable linkers are also coupled to anchor molecules for synthesis of DNA oligonucleotides using on support purification, eliminating time-consuming chromatography and metal cation presence. Oligonucleotides thus obtainded can be directly used for mass analysis, DNA amplification and ligation, hybridization, and many other applications.

  本文介绍了一种调节固体支持物上合成低聚物的合成能力和裂解特性的方法。该方法利用附着在固体表面的连接分子和与表面官能团偶联化合物具有相似反应活性的助偶联剂。优选的连接分子可增加聚合物的密度，提高从支撑表面裂解的阻力。该方法尤其适用于合成寡核苷酸、寡核苷酸微阵列、肽和肽微阵列。稳定的连接体还可与锚分子偶联，用于合成 DNA 寡核苷酸，在支持物上进行纯化，省去了耗时的色谱法和金属阳离子的存在。由此获得的寡核苷酸可直接用于质量分析、DNA 扩增和连接、杂交以及许多其他应用。
• Linkers and co-coupling agents for optimization of oligonucleotide synthesis and purification on solid supports
  申请人：The Regents Of The University Of Michigan

  公开号：US20030120035A1

  公开（公告）日：2003-06-26

  A method of modulation of synthesis capacity on and cleavage properties of synthetic oligomers from solid support is described. The method utilizes linker molecules attached to a solid surface and co-coupling agents that have similar reactivities to the coupling compounds with the surface functional groups. The preferred linker molecules provide an increased density of polymers and more resistance to cleavage from the support surface. The method is particularly useful for synthesis of oligonucleotides, oligonucleotides microarrays, peptides, and peptide microarrays. The stable linkers are also coupled to anchor molecules for synthesis of DNA oligonucleotides using on support purification, eliminating time-consuming chromatography and metal cation presence. Oligonucleotides thus obtained can be directly used for mass analysis, DNA amplification and ligation, hybridization, and many other applications.

  本文介绍了一种调节固体支持物上合成低聚物的合成能力和裂解特性的方法。该方法利用附着在固体表面的连接分子和与表面官能团偶联化合物具有相似反应活性的助偶联剂。优选的连接分子可增加聚合物的密度，提高从支撑表面裂解的阻力。该方法尤其适用于合成寡核苷酸、寡核苷酸微阵列、肽和肽微阵列。这种稳定的连接体还可与锚分子偶联，用于合成 DNA 寡核苷酸，在支持物上进行纯化，省去了耗时的色谱法和金属阳离子的存在。由此获得的寡核苷酸可直接用于质量分析、DNA 扩增和连接、杂交以及许多其他应用。