(2R,5R)-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)-2-(((tertbutyldimethylsilyl)oxy)methyl)tetrahydrofuran-3-yl benzoate | 51549-50-9

• 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: (2R,5R)-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)-2-(((tertbutyldimethylsilyl)oxy)methyl)tetrahydrofuran-3-yl benzoate
• 英文别名: 5'-O-tert-butyldimethylsilyl-3'-O,4-N-dibenzoyl-2'-deoxycytidine；N⁴,O^3'-dibenzoyl-O^5'-(tert-butyl-dimethyl-silanyl)-2'-deoxy-cytidine；[(2R,3S,5R)-5-(4-benzamido-2-oxopyrimidin-1-yl)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-3-yl] benzoate
• CAS: 51549-50-9
• 化学式: C₂₉H₃₅N₃O₆Si
• 分子量: 549.699
• InChiKey: ZUUZERFYJRVHLI-JBRSBNLGSA-N

物化性质

• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.03
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,5R)-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)-2-(((tertbutyldimethylsilyl)oxy)methyl)tetrahydrofuran-3-yl benzoate 在 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以95%的产率得到N4,3'-O-二苯甲酰基-2'-脱氧胞苷
  参考文献：
  名称：

  [EN] NOVEL MODULATORS OF CELL CYCLE CHECKPOINTS AND THEIR USE IN COMBINATION WITH CHECKPOINT KINASE INHIBITORS
  [FR] NOUVEAUX MODULATEURS DE POINTS DE CONTRÔLE DU CYCLE CELLULAIRE ET LEUR UTILISATION EN COMBINAISON AVEC DES INHIBITEURS DE KINASE DE POINT DE CONTRÔLE

  摘要：

  在其多种实施方式中，本发明提供了一类新型的嘧啶类似物，其化学式为（V），作为细胞周期检查点的靶向机制调节剂。可以通过给予本发明的细胞周期检查点调节剂来治疗癌症和/或恶性肿瘤。还讨论了适当的细胞周期检查点调节剂与检查点激酶抑制剂的组合，以在癌细胞中产生协同凋亡。该发明包括通过给予细胞周期检查点调节剂和检查点激酶抑制剂的组合来治疗癌症的方法，以及包含激活剂以及该组合的药物组合和药物配套工具。

  公开号：

  WO2009061781A1
• 作为产物：
  描述：

  2'-脱氧胞嘧啶核苷 在 咪唑 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2R,5R)-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)-2-(((tertbutyldimethylsilyl)oxy)methyl)tetrahydrofuran-3-yl benzoate
  参考文献：
  名称：

  Design and Synthesis of α-Carboxy Phosphononucleosides

  摘要：

  Rhodium catalyzed O-H insertion reactions employing alpha-diazophosphonate 20 with appropriately protected thymidine, uridine, cytosine, adenosine and guanosine derivatives leads to novel 5'-phosphononucleoside derivatives. Deprotection led to a novel series of phosphono derivatives bearing a carboxylic acid moiety adjacent to the phosphonate group with potential antiviral and/or anticancer activity. The phosphononucleosides bearing an alpha-carboxylic acid group are envisaged as potential diphosphate mimics. Conversion to mono- and diphosphorylated phosphononucleosides has been effected for evaluation as nucleoside triphosphate mimics. Most of the novel phosphononucleosides proved to be inactive against a variety of DNA and RNA viruses. Only the phosphono AZT derivatives 56-59 showed weak activity against HIV-1 and HIV-2.

  DOI：

  10.1021/jo101738e

文献信息

• [EN] NOVEL MODULATORS OF CELL CYCLE CHECKPOINTS AND THEIR USE IN COMBINATION WITH CHECKPOINT KINASE INHIBITORS<br/>[FR] NOUVEAUX MODULATEURS DE POINTS DE CONTRÔLE DU CYCLE CELLULAIRE ET LEUR UTILISATION EN COMBINAISON AVEC DES INHIBITEURS DE KINASE DE POINT DE CONTRÔLE
  申请人：SCHERING CORP

  公开号：WO2009061781A1

  公开（公告）日：2009-05-14

  In its many embodiments, the present invention provides a novel class of pyrimidine analogs of formula (V) as targeted mechanism-based modulators of cell cycle checkpoints. Cancers and/or malignancies can be treated by administration of a cell cycle checkpoint modulator of the invention. Also discussed are suitable combinations of the cell cycle checkpoint modulator with a checkpoint kinase inhibitor to produce synergistic apoptosis in cancer cells. The invention includes methods of treating cancers by administering the combination of the cell cycle checkpoint modulator and the checkpoint kinase inhibitor, pharmaceutical compositions comprising the activator as well as the combination and pharmaceutical kits.

  在其多种实施方式中，本发明提供了一类新型的嘧啶类似物，其化学式为（V），作为细胞周期检查点的靶向机制调节剂。可以通过给予本发明的细胞周期检查点调节剂来治疗癌症和/或恶性肿瘤。还讨论了适当的细胞周期检查点调节剂与检查点激酶抑制剂的组合，以在癌细胞中产生协同凋亡。该发明包括通过给予细胞周期检查点调节剂和检查点激酶抑制剂的组合来治疗癌症的方法，以及包含激活剂以及该组合的药物组合和药物配套工具。
• Chemoselective Acylation of Nucleosides
  作者：Yu Tang、Rebecca L. Grange、Oliver D. Engl、Scott J. Miller

  DOI：10.1002/chem.202201661

  日期：2022.9.16

  Chemoselective functionalization of oxygen atoms versus nitrogen atoms in bifunctional and polyfunctional molecules is a long-standing challenge in both fundamental chemistry and in complex molecule synthesis. Different conditions that allow high selectivity in the derivatization of complex nucleosides that contain both O- and N-based functionalities are described. Particularly intriguing cases are

  双功能和多功能分子中氧原子与氮原子的化学选择性功能化是基础化学和复杂分子合成中长期存在的挑战。描述了允许高选择性衍生同时包含O和N官能团的复杂核苷的不同条件。还提出了特别有趣的案例，其中基于O和N的功能的反应性非常依赖于上下文，表现出模糊传统考虑的反应性，但也可以观察到选择性。
• Design and Synthesis of α-Carboxy Phosphononucleosides
  作者：Sebastien Debarge、Jan Balzarini、Anita R. Maguire

  DOI：10.1021/jo101738e

  日期：2011.1.7

  Rhodium catalyzed O-H insertion reactions employing alpha-diazophosphonate 20 with appropriately protected thymidine, uridine, cytosine, adenosine and guanosine derivatives leads to novel 5'-phosphononucleoside derivatives. Deprotection led to a novel series of phosphono derivatives bearing a carboxylic acid moiety adjacent to the phosphonate group with potential antiviral and/or anticancer activity. The phosphononucleosides bearing an alpha-carboxylic acid group are envisaged as potential diphosphate mimics. Conversion to mono- and diphosphorylated phosphononucleosides has been effected for evaluation as nucleoside triphosphate mimics. Most of the novel phosphononucleosides proved to be inactive against a variety of DNA and RNA viruses. Only the phosphono AZT derivatives 56-59 showed weak activity against HIV-1 and HIV-2.