((2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl bis(S-pivaloyl-2-mercaptoethan-1-yl)phosphate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: ((2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl bis(S-pivaloyl-2-mercaptoethan-1-yl)phosphate
• 英文别名: 1-[β-D-arabinofuranosyl]cytosine-5'-bis(S-pivaloyl-2-thioethyl)phosphate；bis(tBuSATE) phosphotriester；Bis(tBuSATE)Ara-C-MP；S-[2-[[(2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-[2-(2,2-dimethylpropanoylsulfanyl)ethoxy]phosphoryl]oxyethyl] 2,2-dimethylpropanethioate
• 化学式: C₂₃H₃₈N₃O₁₀PS₂
• 分子量: 611.675
• InChiKey: PWAAFXOVBFKSKU-NRSFXHEJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  39
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  238
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  阿糖胞苷 在 吡啶 、 咪唑 、 四氮唑 、 盐酸 、 叔丁基过氧化氢 、 4-二甲氨基吡啶 、 triethylamine trihydrofluoride 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 癸烷 、 乙腈 为溶剂， 反应 42.0h， 生成 ((2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl bis(S-pivaloyl-2-mercaptoethan-1-yl)phosphate
  参考文献：
  名称：

  Synthetic Approaches to a Mononucleotide Prodrug of Cytarabine

  摘要：

  Synthetic pathways to a mononucleotide prodrug of cytarabine (Ara-C) bearing S-pivaloyl-2-thioethyl (tBuSATE) groups, as biolabile phosphate protections, are reported. Using a common phosphoramidite approach, two different kinds of nucleoside protecting groups have been investigated. During this study, we observed an intermolecular migration of the Boc protecting group in the course of the tert-butyldimethylsilyl ether cleavage using tetrabutyl ammonium fluoride.

  DOI：

  10.1080/15257770500267006

文献信息

• THIONUCLEOSIDE DERIVATIVE OR SALT THEREOF, AND PHARMACEUTICAL COMPOSITION
  申请人：FUJIFILM Corporation

  公开号：US20170233429A1

  公开（公告）日：2017-08-17

  Disclosed are a compound and a pharmaceutical composition that exhibit an excellent drug efficacy against a tumor, in particular a tumor which has acquired resistance to gemcitabine. Specifically, provided is a thionucleoside derivative represented by General Formula [1] (in the formula, R 1 represents a hydroxyl group which may be protected, a C 1-20 alkoxy group which may be substituted, or the like; R 2 represents a C 1-20 alkoxy group which may be substituted, a C 3-8 cycloalkoxy group which may be substituted, or the like; and R 3 represents a hydrogen atom or the like); or a salt thereof. Further, provided is a pharmaceutical composition containing such a thionucleoside derivative or a salt thereof.

  揭示了一种化合物和药物组合物，对抗抗对吉西他滨产生耐药性的肿瘤表现出优异的药效。具体来说，提供了一种由通用式[1]表示的硫代核苷衍生物 （在公式中，R1代表可能被保护的羟基、可能被取代的C1-20烷氧基等；R2代表可能被取代的C1-20烷氧基、可能被取代的C3-8环烷氧基等；R3代表氢原子等）或其盐。此外，提供了含有这种硫代核苷衍生物或其盐的药物组合物。
• Thionucleoside derivative or salt thereof, and pharmaceutical composition
  申请人：FUJIFILM Corporation

  公开号：US10059734B2

  公开（公告）日：2018-08-28

  Disclosed are a compound and a pharmaceutical composition that exhibit an excellent drug efficacy against a tumor, in particular a tumor which has acquired resistance to gemcitabine. Specifically, provided is a thionucleoside derivative represented by General Formula [1] (in the formula, R1 represents a hydroxyl group which may be protected, a C1-20 alkoxy group which may be substituted, or the like; R2 represents a C1-20 alkoxy group which may be substituted, a C3-8 cycloalkoxy group which may be substituted, or the like; and R3 represents a hydrogen atom or the like); or a salt thereof. Further, provided is a pharmaceutical composition containing such a thionucleoside derivative or a salt thereof.

  本发明公开了一种化合物和药物组合物，该化合物和药物组合物对肿瘤，特别是对吉西他滨产生抗药性的肿瘤具有极佳的药效。具体而言，提供了一种由通式[1]表示的硫代核苷衍生物 (式中，R1 代表可被保护的羟基、可被取代的 C1-20 烷氧基或类似基团；R2 代表可被取代的 C1-20 烷氧基、可被取代的 C3-8 环烷氧基或类似基团；R3 代表氢原子或类似基团）；或其盐。此外，还提供了一种含有这种硫代核苷衍生物或其盐的药物组合物。
• Prodrugs of Ara-CMP and Ara-AMP with a<i>S</i>-Acyl-2-thioethyl (SATE) Biolabile Phosphate Protecting Group: Synthesis and Biological Evaluation
  作者：R. Bazzanini、S. Manfredini、E. Durini、B. Gröschel、J. Cinatl、J. Balzarini、E. De Clercq、J-L. Imbach、C. Périgaud、G. Gosselin

  DOI：10.1080/15257779908041616

  日期：1999.4

  The bis(S-pivaloyl-2-thioethyl) phosphotriesters of Ara-C and Ara-A were synthesized as potential bioreversible mononucleotide prodrugs. Some N- and O-acylated derivatives were also prepared with the aim to modify the lipophilicity of the title pronucleotides. Compounds were tested far their antitumor/antiviral activity against a variety of tumor cells and viruses.
• [EN] THIONUCLEOSIDE DERIVATIVE OR SALT THEREOF, AND PHARMACEUTICAL COMPOSITION<br/>[FR] DÉRIVÉ DE THIONUCLÉOSIDE OU SEL DE CELUI-CI, ET COMPOSITION PHARMACEUTIQUE<br/>[JA] チオヌクレオシド誘導体またはその塩および医薬組成物
  申请人：FUJIFILM CORP

  公开号：WO2016068341A1

  公开（公告）日：2016-05-06

  　本発明の課題は、腫瘍、特にゲムシタビン耐性を獲得した腫瘍に対して優れた薬効を示す化合物および医薬組成物を提供するである。本発明は、一般式[１] （式中、Ｒ１は、保護されていてもよいヒドロキシル基または置換されていてもよいＣ１－２０アルコキシ基などを示し；Ｒ２は、置換されていてもよいＣ１－２０アルコキシ基または置換されていてもよいＣ３－８シクロアルコキシ基などを示し；Ｒ３は、水素原子などを示す。）で表されるチオヌクレオシド誘導体またはその塩を提供する。また、これらのチオヌクレオシド誘導体またはその塩を含有する医薬組成物を提供する。