N-4,O-3′-dibenzoyl-gemcytabine | 1020657-43-5

• 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: N-4,O-3′-dibenzoyl-gemcytabine
• 英文别名: N⁴,O-^3’-dibenzoyl-2’,2’-difluoro-2-deoxycytidine；N⁴,O^3′-dibenzoylgemcitabine；N,O3'-dibenzoylgemcitabine；[(2R,3R,5R)-5-(4-benzamido-2-oxopyrimidin-1-yl)-4,4-difluoro-2-(hydroxymethyl)oxolan-3-yl] benzoate
• CAS: 1020657-43-5
• 化学式: C₂₃H₁₉F₂N₃O₆
• 分子量: 471.417
• InChiKey: DHFVAACQVXHOHI-HGHGUNKESA-N

物化性质

• 熔点：
  195-197oC
• 溶解度：
  可溶于DMSO（轻微）、甲醇（轻微、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-4,O-3′-dibenzoyl-gemcytabine 在 甲基三苯氧基碘磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以84%的产率得到[(2S,3R,5R)-5-(4-benzamido-2-oxopyrimidin-1-yl)-4,4-difluoro-2-(iodomethyl)oxolan-3-yl] benzoate
  参考文献：
  名称：

  5'-氨基-2'，5'-二脱氧-2'，2'-二氟胞苷衍生物的合成作为新型抗癌核苷类似物

  摘要：

  为了鉴定抗癌核苷类似物，已经合成了新型的5'-氨基-2'，5'-二脱氧-2'，2'-二氟胞苷衍生物。设计并实施了几种合成路线，这些路线依靠S N 2置换或还原胺化来提供所需的衍生物。

  DOI：

  10.1016/j.tetlet.2013.11.018
• 作为产物：
  描述：

  盐酸吉西他滨 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.5h， 生成 N-4,O-3′-dibenzoyl-gemcytabine
  参考文献：
  名称：

  5'-氨基-2'，5'-二脱氧-2'，2'-二氟胞苷衍生物的合成作为新型抗癌核苷类似物

  摘要：

  为了鉴定抗癌核苷类似物，已经合成了新型的5'-氨基-2'，5'-二脱氧-2'，2'-二氟胞苷衍生物。设计并实施了几种合成路线，这些路线依靠S N 2置换或还原胺化来提供所需的衍生物。

  DOI：

  10.1016/j.tetlet.2013.11.018

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。
• Efficient Synthesis of Gemcitabine 5′-O-Triphosphate Using Gemcitabine 5′-O-Phosphoramidate as an Intermediate
  作者：Janina Baraniak、Renata Kaczmarek、Ewa Radzikowska

  DOI：10.1055/s-0034-1378353

  日期：——

  A new efficient approach for the synthesis of gemcitabine triphosphate has been developed. The method is based on the ring-opening reaction of 2-cyanoethoxy-2-oxo-1,3,2-oxathia­phospholane with protected gemcitabine in the presence of DBU. Subsequent treatment of gemcitabine monophosphate with DCC in the presence of ammonia provides gemcitabine 5′-O-phosphoramidate. Finally, this compound, on reaction

  已开发出一种新的有效合成吉西他滨三磷酸的方法。该方法基于 2-cyanoethoxy-2-oxo-1,3,2-oxathiaphospholane 与受保护的吉西他滨在 DBU 存在下的开环反应。随后在氨存在下用 DCC 处理吉西他滨单磷酸盐，提供吉西他滨 5'-O-氨基磷酸酯。最后，该化合物与焦磷酸盐反应后，以 50% 的产率提供吉西他滨 5'-三磷酸盐。
• [EN] SALT OF TRIPHOSPHATE PHOSPHORAMIDATES OF NUCLEOTIDES AS ANTICANCER COMPOUNDS<br/>[FR] SEL DE PHOSPHORAMIDATES DE TRIPHOSPHATE DE NUCLÉOTIDES EN TANT QUE COMPOSÉS ANTICANCÉREUX
  申请人：NUCANA PLC

  公开号：WO2020201751A1

  公开（公告）日：2020-10-08

  The present invention relates to salts of triphosphate phosphoramidates which are useful in the treatment of cancer.

  本发明涉及三磷酸三酯磷酰胺盐，可用于癌症治疗。
• [EN] MODULATORS OF CELL CYCLE CHECKPOINTS AND THEIR USE IN COMBINATION WITH CHECKPOINT KINASE INHIBITORS<br/>[FR] 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：WO2011028638A1

  公开（公告）日：2011-03-10

  In its many embodiments, the present invention provides a novel class of pyrimidine analogs 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 also includes methods of treating cancers by administering the combination of the cell cycle checkpoint modulator and the checkpoint kinase inhibitor, pharmaceutical compositions comprising the cell cycle checkpoint modulator as well as combinations and pharmaceutical kits. An example cell cycle checkpoint modulator is shown below: formula (I).

  在其多种实施方式中，本发明提供了一种新型嘧啶类似物作为细胞周期检查点的靶向机制调节剂。通过给予该发明的细胞周期检查点调节剂，可以治疗癌症和/或恶性肿瘤。本发明还讨论了细胞周期检查点调节剂与检查点激酶抑制剂的合适组合，以产生对癌细胞的协同凋亡。本发明还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物来治疗癌症的方法，以及包含细胞周期检查点调节剂的制药组合物和组合物制药套件。下面是一个例子细胞周期检查点调节剂的公式（I）。
• N-Acyl-phosphoramidates as potential novel form of gemcitabine prodrugs
  作者：Janina Baraniak、Aleksandra Pietkiewicz、Renata Kaczmarek、Ewa Radzikowska、Katarzyna Kulik、Karolina Krolewska、Marcin Cieslak、Agnieszka Krakowiak、Barbara Nawrot

  DOI：10.1016/j.bmc.2014.02.034

  日期：2014.4

  Gemcitabine (dFdC) is a cytidine analog remarkably active against a wide range of solid tumors. Inside a cell, gemcitabine is phosphorylated by deoxycytidine kinase to yield gemcitabine monophosphate, further converted to gemcitabine di- and triphosphate. The most frequent form of acquired resistance to gemcitabine in vitro is the deoxycytidine kinase deficiency. Thus, proper prodrugs carrying the 5'-pdFdC moiety may help to overcome this problem. A series of new derivatives of gemcitabine possessing N-acyl(thio) phosphoramidate moieties were prepared and their cytotoxic properties were determined. N-Acyl-phosphoramidate derivatives of gemcitabine have similar cytotoxicity as gemcitabine itself, and have been found accessible to the cellular enzymes. The nicotinic carboxamide derivative of gemcitabine 5'-O-phosphorothioate occurred to be the best inhibitor of bacterial DNA polymerase I and human DNA polymerase alpha. (C) 2014 Elsevier Ltd. All rights reserved.