2'-deoxy-2',2',5-trifluorocytidine | 132786-38-0

• 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: 2'-deoxy-2',2',5-trifluorocytidine
• 英文别名: 4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-fluoropyrimidin-2-one
• CAS: 132786-38-0
• 化学式: C₉H₁₀F₃N₃O₄
• 分子量: 281.191
• InChiKey: IEBJQCKQGMUTHO-WYDQCIBASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2'-deoxy-2',2',5-trifluorocytidine 在 盐酸 作用下， 以 水 为溶剂， 以89%的产率得到2'-deoxy-2',2',5-trifluorocytidine hydrochloride
  参考文献：
  名称：

  [EN] MULTITARGETED NUCLEOSIDE DERIVATIVES
  [FR] DÉRIVÉS DE NUCLÉOSIDE MULTICIBLES

  摘要：

  多靶向嘧啶核苷卡巴酯，其在碱基和糖部分均取代有氟（见式I），其中R = 直链或支链烷基（C1-7）；R' = H，羟基保护基团；R" = H，磷酸酯，氨基酸烷基（C1-酯磷酸酰胺，或磷酸二胺基。所披露的化合物是氟代嘧啶前药，其具有一种新颖的结构组分组合，可提供能够1）抑制细胞合成和DNA正常功能所需的多种细胞酶的细胞内代谢产物，以及2）通过错误插入到DNA中引起DNA损伤。通过作用于具有不同作用机制的多个靶点，式I的化合物降低了核苷类抗癌和抗病毒药物使用的主要缺点之一，即药物耐药性的出现可能性。

  公开号：

  WO2018200859A1
• 作为产物：
  描述：

  3',5'-di-O-benzoyl-2'deoxy-2',2',5-trifluorocytidine 在 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 以5.85 g的产率得到2'-deoxy-2',2',5-trifluorocytidine
  参考文献：
  名称：

  [EN] MULTITARGETED NUCLEOSIDE DERIVATIVES
  [FR] DÉRIVÉS DE NUCLÉOSIDE MULTICIBLES

  摘要：

  多靶向嘧啶核苷卡巴酯，其在碱基和糖部分均取代有氟（见式I），其中R = 直链或支链烷基（C1-7）；R' = H，羟基保护基团；R" = H，磷酸酯，氨基酸烷基（C1-酯磷酸酰胺，或磷酸二胺基。所披露的化合物是氟代嘧啶前药，其具有一种新颖的结构组分组合，可提供能够1）抑制细胞合成和DNA正常功能所需的多种细胞酶的细胞内代谢产物，以及2）通过错误插入到DNA中引起DNA损伤。通过作用于具有不同作用机制的多个靶点，式I的化合物降低了核苷类抗癌和抗病毒药物使用的主要缺点之一，即药物耐药性的出现可能性。

  公开号：

  WO2018200859A1

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。
• Rational Design of an Orally Active Anticancer Fluoropyrimidine, Pencitabine, a Hybrid of Capecitabine and Gemcitabine
  作者：Thomas I. Kalman

  DOI：10.1021/acsmedchemlett.1c00565

  日期：2022.3.10

  parent drugs. Pencitabine is postulated to interfere with DNA synthesis and function by inhibiting multiple nucleotide-metabolizing enzymes and by misincorporation into DNA. Based on detailed mechanistic analyses and literature precedents, the hypothesis is put forward that the significant DNA damage caused by pencitabine may be accounted for by two additional effects not shown by the parent drugs: inhibition

  抗癌药物卡培他滨的结构经过重新设计，以防止代谢转化为 5-氟尿嘧啶及其相关的潜在致命毒性。由此产生的胞苷类似物喷西他滨是卡培他滨和吉西他滨的混合体，吉西他滨是临床使用的另一种抗癌药物。初步生物学评估表明，培西他滨在体外细胞培养物中具有细胞毒性，在体内具有口服活性在人类异种移植测试系统中。Pencitabine 可以模拟其母体药物的已知治疗优势组合。据推测，Pencitabine 通过抑制多种核苷酸代谢酶和错误掺入 DNA 来干扰 DNA 合成和功能。基于详细的机制分析和文献先例，提出了一个假设，即喷西他滨引起的显着 DNA 损伤可能是由母体药物未显示的两种额外作用造成的：抑制参与碱基切除修复的 DNA 糖基化酶和 DNA（ cytosine-5)-methyltransferase 参与细胞代谢的表观遗传调控。
• Multitargeted nucleoside derivatives
  申请人：Kalman Thomas I.

  公开号：US10751358B2

  公开（公告）日：2020-08-25

  Multitargeted pyrimidine nucleoside carbamates, substituted with fluorine at both the base and the sugar moieties, are disclosed (see Formula I): where R=linear or branched alkyl (C1-7); R′=H, hydroxy protecting group; R″=H, phosphate ester, amino acid alkyl (C1-7) ester phoshoramidate, or phosphorodiamidate. The disclosed compounds are fluoropyrimidine prodrugs that are characterized by a novel combination of structural components that provide intracellular metabolites capable of 1) inhibiting several cellular enzymes required for the synthesis and proper functioning of DNA, and 2) causing DNA damage by misincorporation into DNA. By acting on multiple targets with different mechanisms of action, compounds of Formula I reduce the likelihood of the emergence of drug resistance, a major drawback of the use of nucleoside-based anticancer and antiviral drugs. Due to the metabolic activation profile of compounds of Formula I, characteristic adverse effects and potential lethality of the fluoropyrimidine class of anticancer drugs may be alleviated. Compounds and compositions of the present disclosure can be used in treatment of cancer and viral infections.

  多靶点嘧啶核苷氨基甲酸酯的碱基和糖基均被氟取代（见式 I）： 其中，R=直链或支链烷基（C1-7）；R′=H，羟基保护基；R″=H，磷酸酯，氨基酸烷基（C1-7）酯磷酰胺酯或磷酰二酰胺酯。所公开的化合物是氟嘧啶原药，其特点是结构成分的新颖组合，提供的细胞内代谢物能够：1）抑制 DNA 合成和正常功能所需的几种细胞酶；2）通过误入 DNA 造成 DNA 损伤。通过作用于具有不同作用机制的多个靶点，式 I 化合物降低了出现耐药性的可能性，而耐药性是使用核苷类抗癌和抗病毒药物的一个主要缺点。由于式 I 化合物的代谢活化特征，可减轻氟嘧啶类抗癌药物的特征性不良反应和潜在致死性。本公开的化合物和组合物可用于治疗癌症和病毒感染。
• NOVEL MODULATORS OF CELL CYCLE CHECKPOINTS AND THEIR USE IN COMBINATION WITH CHECKPOINT KINASE INHIBITORS
  申请人：Guzi Timothy J.

  公开号：US20110183933A1

  公开（公告）日：2011-07-28

  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.
• MULTITARGETED NUCLEOSIDE DERIVATIVES
  申请人：Kalman Thomas I.

  公开号：US20200054661A1

  公开（公告）日：2020-02-20

  Multitargeted pyrimidine nucleoside carbamates, substituted with fluorine at both the base and the sugar moieties, are disclosed (see Formula I): where R=linear or branched alkyl (C 1-7 ); R′=H, hydroxy protecting group; R″=H, phosphate ester, amino acid alkyl (C 1-7 ) ester phoshoramidate, or phosphorodiamidate. The disclosed compounds are fluoropyrimidine prodrugs that are characterized by a novel combination of structural components that provide intracellular metabolites capable of 1) inhibiting several cellular enzymes required for the synthesis and proper functioning of DNA, and 2) causing DNA damage by misincorporation into DNA. By acting on multiple targets with different mechanisms of action, compounds of Formula I reduce the likelihood of the emergence of drug resistance, a major drawback of the use of nucleoside-based anticancer and antiviral drugs. Due to the metabolic activation profile of compounds of Formula I, characteristic adverse effects and potential lethality of the fluoropyrimidine class of anticancer drugs may be alleviated. Compounds and compositions of the present disclosure can be used in treatment of cancer and viral infections.