[(2R,3R,4R,5R)-5-(4-amino-5-cyanopyrrolo[2,3-d]pyrimidin-7-yl)-4-benzoyloxy-2-[(1R)-1-benzoyloxybut-3-enyl]oxolan-3-yl] benzoate | 332363-33-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡咯并嘧啶核苷和核苷酸
• 英文名称: [(2R,3R,4R,5R)-5-(4-amino-5-cyanopyrrolo[2,3-d]pyrimidin-7-yl)-4-benzoyloxy-2-[(1R)-1-benzoyloxybut-3-enyl]oxolan-3-yl] benzoate
• CAS: 332363-33-4
• 化学式: C₃₆H₂₉N₅O₇
• 分子量: 643.656
• InChiKey: PENWDFRVZCIYJA-QANMIMMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  48
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  169
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  [(2R,3R,4R,5R)-5-(4-amino-5-cyanopyrrolo[2,3-d]pyrimidin-7-yl)-4-benzoyloxy-2-[(1R)-1-benzoyloxybut-3-enyl]oxolan-3-yl] benzoate 在 氨 、 sodium acetate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以145 mg的产率得到4-amino-5-cyano-7-(5(R)-C-allyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Synthesis and cytotoxicity of 4′-C- and 5′-C-substituted toyocamycins

  摘要：

  Toyocamycin and some analogues have shown potent antitumor activities; however, none of them could be used clinically primarily owing to their cytotoxicity to normal human cells. In order to overcome the weakness of these nucleoside analogues, substitution of a variety of modified sugars for the ribofuranose was explored in our laboratories with expectation that certain sugar-modified toyocamycin analogues may be selectively cytotoxic to cancer cells. In this article, we report synthesis and cytotoxicity of 4'-C- and T-C-substituted toyocamycins, which were prepared via the condensations of 4-C- and 5-C-substituted ribofuranose derivatives 11, 12, 13, 20, 21, and 26 with the silylated form of 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]py (27) and subsequent debromination and debenzoylation. When compared to the parent toyocamycin, all these analogues showed much lower cytotoxicity to human prostate cancer cells (HTB-81), mouse melanoma cancer cells (B16) as well as normal human fibroblasts. Compound le showed a significant cytotoxicity to the prostate cancer cells and a moderate selectivity. The results suggested that sugar modifications, especially those that may affect phosphorylation of nucleosides, could alter cytotoxicity profile significantly. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00221-2
• 作为产物：
  描述：

  1-O-acetyl-2,3,5-tri-O-benzoyl-5(R)-C-allyl-D-ribofuranose 在 ammonium sulfate 、 溶剂黄146 、 六甲基二硅氮烷 、 锌 作用下， 以 间二甲苯 为溶剂， 反应 83.0h， 生成 [(2R,3R,4R,5R)-5-(4-amino-5-cyanopyrrolo[2,3-d]pyrimidin-7-yl)-4-benzoyloxy-2-[(1R)-1-benzoyloxybut-3-enyl]oxolan-3-yl] benzoate
  参考文献：
  名称：

  Synthesis and cytotoxicity of 4′-C- and 5′-C-substituted toyocamycins

  摘要：

  Toyocamycin and some analogues have shown potent antitumor activities; however, none of them could be used clinically primarily owing to their cytotoxicity to normal human cells. In order to overcome the weakness of these nucleoside analogues, substitution of a variety of modified sugars for the ribofuranose was explored in our laboratories with expectation that certain sugar-modified toyocamycin analogues may be selectively cytotoxic to cancer cells. In this article, we report synthesis and cytotoxicity of 4'-C- and T-C-substituted toyocamycins, which were prepared via the condensations of 4-C- and 5-C-substituted ribofuranose derivatives 11, 12, 13, 20, 21, and 26 with the silylated form of 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]py (27) and subsequent debromination and debenzoylation. When compared to the parent toyocamycin, all these analogues showed much lower cytotoxicity to human prostate cancer cells (HTB-81), mouse melanoma cancer cells (B16) as well as normal human fibroblasts. Compound le showed a significant cytotoxicity to the prostate cancer cells and a moderate selectivity. The results suggested that sugar modifications, especially those that may affect phosphorylation of nucleosides, could alter cytotoxicity profile significantly. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00221-2

文献信息

• Pyrrolo[2,3-d]pyrimidine nucleoside analogs
  申请人：——

  公开号：US20020035077A1

  公开（公告）日：2002-03-21

  Compositions and methods for pyrrolo[2,3-d]pyrimidine nucleoside analogs having substituents at the C4′ and C5′ positions of the ribofuranose moiety are presented. Contemplated compositions exhibit, among other things, anti-cancer and immunomodulating effects at reduced cytotoxicity.

  本发明提供了在核糖苷骨架的C4'和C5'位置具有取代基的吡咯[2,3-d]嘧啶核苷类似物的组合物和方法。考虑到的组合物在减少细胞毒性的情况下表现出抗癌和免疫调节等效果。
• US6831069B2
  申请人：——

  公开号：US6831069B2

  公开（公告）日：2004-12-14
• Synthesis and cytotoxicity of 4′-C- and 5′-C-substituted toyocamycins
  作者：Esmir Gunic、Jean-Luc Girardet、Zbigniew Pietrzkowski、Cathey Esler、Guangyi Wang

  DOI：10.1016/s0968-0896(00)00221-2

  日期：2001.1

  Toyocamycin and some analogues have shown potent antitumor activities; however, none of them could be used clinically primarily owing to their cytotoxicity to normal human cells. In order to overcome the weakness of these nucleoside analogues, substitution of a variety of modified sugars for the ribofuranose was explored in our laboratories with expectation that certain sugar-modified toyocamycin analogues may be selectively cytotoxic to cancer cells. In this article, we report synthesis and cytotoxicity of 4'-C- and T-C-substituted toyocamycins, which were prepared via the condensations of 4-C- and 5-C-substituted ribofuranose derivatives 11, 12, 13, 20, 21, and 26 with the silylated form of 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]py (27) and subsequent debromination and debenzoylation. When compared to the parent toyocamycin, all these analogues showed much lower cytotoxicity to human prostate cancer cells (HTB-81), mouse melanoma cancer cells (B16) as well as normal human fibroblasts. Compound le showed a significant cytotoxicity to the prostate cancer cells and a moderate selectivity. The results suggested that sugar modifications, especially those that may affect phosphorylation of nucleosides, could alter cytotoxicity profile significantly. (C) 2000 Elsevier Science Ltd. All rights reserved.