S-(2-(((RS)-(((2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)oxy)ethyl) 2,2-dimethylpropanethioate | 1192047-66-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: S-(2-(((RS)-(((2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)oxy)ethyl) 2,2-dimethylpropanethioate
• 英文别名: O-[β-D-arabinofuranosylcytosine]-O'-(S-pivaloyl-2-thioethyl)-O''-phenylphosphate；S-[2-[[(2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-phenoxyphosphoryl]oxyethyl] 2,2-dimethylpropanethioate
• CAS: 1192047-66-7
• 化学式: C₂₂H₃₀N₃O₉PS
• 分子量: 543.535
• InChiKey: IPYYTSFLJBGUIQ-WEMLERLQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  196
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  O-[4-N,N-2',3'-O-tetra-(tert-butyloxycarbonyl)-β-D-arabinofuranosylcytosine]-O'-(S-pivaloyl-2-thioethyl)-O''-phenylphosphate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.25h， 以67%的产率得到S-(2-(((RS)-(((2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)oxy)ethyl) 2,2-dimethylpropanethioate
  参考文献：
  名称：

  Special feature of mixed phosphotriester derivatives of cytarabine

  摘要：

  Despite the unquestionable therapeutic interest of bis(SATE) pronucleotides, a presystemic metabolism preventing the delivery of the prodrugs in target cancer cells or tumours may constitute a limitation to the in vivo development of such derivatives. In order to overcome these drawbacks several strategies have been envisaged and we report herein the application of the S-acyl-2-thioethyl (SATE) phenyl pronucleotide approach to the well-known cytotoxic nucleoside cytosine-1-beta-D-arabinofuranoside (cytarabine, araC). We describe modifications of the SATE moieties with the introduction of polar groups on the acyl residue, in order to study how these changes affect antitumoral activity and metabolic stability. Two different synthetic pathways were explored and lead to obtain the corresponding mixed derivatives in satisfactory yields. Cytotoxicity was studied in murine leukaemia cells L1210 as well as in cells derived from solid human tumours (Messa and MCF7). Biological evaluation of these compounds in cell culture experiments with nucleoside analogue-sensitive and resistant cell lines showed that the modified compounds were active at higher concentrations than unmodified cytarabine, yet were much able to partially reverse resistance due to deficient nucleoside transport or activation. These results can be correlated with an incomplete decomposition mechanism into the corresponding 5'-mononucleotide. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.038

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。
• [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。