1-<5-O-benzyl-3-C-<(benzyloxy)methyl>-3-deoxy-β-D-erythro-pentofuranosyl>thymine | 133713-72-1

• 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: 1-<5-O-benzyl-3-C-<(benzyloxy)methyl>-3-deoxy-β-D-erythro-pentofuranosyl>thymine
• 英文别名: 1-[(2R,3R,4S,5S)-3-hydroxy-4,5-bis(phenylmethoxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 133713-72-1
• 化学式: C₂₅H₂₈N₂O₆
• 分子量: 452.507
• InChiKey: YGPWGQNUPKSGEU-GBEXAXCTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-<5-O-benzyl-3-C-<(benzyloxy)methyl>-3-deoxy-β-D-erythro-pentofuranosyl>thymine 在 吡啶 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 139.0h， 生成 1-<5-O-benzyl-3-C-<(benzyloxy)methyl>-3-deoxy-β-D-threo-pentofuranosyl>thymine
  参考文献：
  名称：

  Syntheses and biological evaluations of 3'-deoxy-3'-C-branched-chain-substituted nucleosides

  摘要：

  Various 3'-deoxy-3'-C-(hydroxymethyl)-, 3'-deoxy-3'-C-(fluoromethyl)-, 3'-deoxy-3'-C-(azidomethyl)-, and 3'-deoxy-3'-C-(aminomethyl)-substituted nucleosides (total 12 compounds) have been synthesized and evaluated against L1210, P388, S-180, and CCRF-CEM cells and HSV-1, HSV-2, and HIV-1 in culture. Only 3'-deoxy-3'-C-(hydroxymethyl)thymidine (36) was found to show significant anticancer activity against L1210, P388, S-180, and CCRF-CEM cells with ED50 values of 50, 5, 10, and 1 muM, respectively. None of these compounds demonstrated significant antiviral activity against HSV-1, HSV-2, or HIV-1. These compounds were also evaluated against thymidine kinases derived from HSV-1 (strain KOS), HSV-2 (strain 333), and mammalian (K562) cells. The thymidine kinase (HSV-1 strain KOS) was inhibited significantly by both 3'-deoxy-3'-C-(hydroxymethyl)- and 3'-deoxy-3'-C-(fluoromethyl)thymidine.

  DOI：

  10.1021/jm00055a006
• 作为产物：
  描述：

  胸腺嘧啶 在 C₄F₉SO₃K 、 氨 、 六甲基二硅氮烷 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 48.0h， 生成 1-<5-O-benzyl-3-C-<(benzyloxy)methyl>-3-deoxy-β-D-erythro-pentofuranosyl>thymine
  参考文献：
  名称：

  Syntheses and biological evaluations of 3'-deoxy-3'-C-branched-chain-substituted nucleosides

  摘要：

  Various 3'-deoxy-3'-C-(hydroxymethyl)-, 3'-deoxy-3'-C-(fluoromethyl)-, 3'-deoxy-3'-C-(azidomethyl)-, and 3'-deoxy-3'-C-(aminomethyl)-substituted nucleosides (total 12 compounds) have been synthesized and evaluated against L1210, P388, S-180, and CCRF-CEM cells and HSV-1, HSV-2, and HIV-1 in culture. Only 3'-deoxy-3'-C-(hydroxymethyl)thymidine (36) was found to show significant anticancer activity against L1210, P388, S-180, and CCRF-CEM cells with ED50 values of 50, 5, 10, and 1 muM, respectively. None of these compounds demonstrated significant antiviral activity against HSV-1, HSV-2, or HIV-1. These compounds were also evaluated against thymidine kinases derived from HSV-1 (strain KOS), HSV-2 (strain 333), and mammalian (K562) cells. The thymidine kinase (HSV-1 strain KOS) was inhibited significantly by both 3'-deoxy-3'-C-(hydroxymethyl)- and 3'-deoxy-3'-C-(fluoromethyl)thymidine.

  DOI：

  10.1021/jm00055a006

文献信息

• 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。
• Syntheses and biological evaluations of 3'-deoxy-3'-C-branched-chain-substituted nucleosides
  作者：Tai Shun Lin、Ju Liang Zhu、Ginger E. Dutschman、Yung Chi Cheng、William H. Prusoff

  DOI：10.1021/jm00055a006

  日期：1993.2

  Various 3'-deoxy-3'-C-(hydroxymethyl)-, 3'-deoxy-3'-C-(fluoromethyl)-, 3'-deoxy-3'-C-(azidomethyl)-, and 3'-deoxy-3'-C-(aminomethyl)-substituted nucleosides (total 12 compounds) have been synthesized and evaluated against L1210, P388, S-180, and CCRF-CEM cells and HSV-1, HSV-2, and HIV-1 in culture. Only 3'-deoxy-3'-C-(hydroxymethyl)thymidine (36) was found to show significant anticancer activity against L1210, P388, S-180, and CCRF-CEM cells with ED50 values of 50, 5, 10, and 1 muM, respectively. None of these compounds demonstrated significant antiviral activity against HSV-1, HSV-2, or HIV-1. These compounds were also evaluated against thymidine kinases derived from HSV-1 (strain KOS), HSV-2 (strain 333), and mammalian (K562) cells. The thymidine kinase (HSV-1 strain KOS) was inhibited significantly by both 3'-deoxy-3'-C-(hydroxymethyl)- and 3'-deoxy-3'-C-(fluoromethyl)thymidine.