4-(hydroxymethyl)phenyl decanoate | 1604841-65-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 4-(hydroxymethyl)phenyl decanoate
• 英文别名: [4-(Hydroxymethyl)phenyl] decanoate
• CAS: 1604841-65-7
• 化学式: C₁₇H₂₆O₃
• 分子量: 278.392
• InChiKey: BEHVFHYNDMKTIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.23
• 重原子数：
  20.0
• 可旋转键数：
  10.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-(hydroxymethyl)phenyl decanoate 在 4,5-二氰基咪唑 作用下， 以 乙腈 为溶剂， 反应 0.75h， 生成
  参考文献：
  名称：

  Nucleoside Diphosphate Prodrugs: Nonsymmetric DiPPro-Nucleotides

  摘要：

  Nonsymmetric DiPPro-nucleotides are described as nucleoside diphosphate (NDP) delivery systems. The concept is to attach different bis(acyloxybenzyl) moieties at the beta-phosphate moiety of a NDP. DiPPro compounds bearing two alkanoylbenzyl residues and DiPPro compounds bearing an alkanoylbenzyl or a benzoylbenzyl group as bioreversible prodrug moieties were studied. Compounds bearing short chain alkanoyl esters led to a fast hydrolysis by chemical or enzymatic means. The ester group in the second prodrug group comprised a long lipophilic aliphatic or an aromatic residue. The lipophilicity of this group enabled the prodrug to penetrate the cell membrane. The introduction of two different groups allowed a controlled stepwise removal of the prodrug moieties to achieve a highly selective delivery of the ND? in CEM cell extracts. The compounds were highly active against HIV even in thymidine ldnase-deficient CEM cells. Thus, the compounds, although charged at the a-phosphate group, were taken up by the cells and released NDPs.

  DOI：

  10.1021/acs.jmedchem.5b00737
• 作为产物：
  描述：

  对羟基苯甲醇 、 癸酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 以57%的产率得到4-(hydroxymethyl)phenyl decanoate
  参考文献：
  名称：

  DiPPro方法：亲脂性d4T二磷酸前药的合成，水解和抗病毒活性

  摘要：

  提出了作为双（酰氧基苄基）磷酸酯的核苷二磷酸酯（NDPs）的β-磷酸酯基团的生物可逆保护。为了研究这些潜在的NDP前药（Di PP ro药物）的结构活性关系，合成了一系列Di PP ro化合物，它们带有各种长度的脂肪酸和d4T作为模型核苷。为了合成亲脂性修饰的二磷酸基团，使预先形成的亚磷酰胺与核苷酸反应，然后使β- PIII随后氧化部分。在不同的介质（例如磷酸盐缓冲液（pH 7.3）或CEM细胞提取物）中研究了这些前药的化学和酶稳定性。在所有介质中，水解速率显然取决于酰基部分，并且随着烷基链长度的增加而降低。由于存在酶催化的裂解，这些化合物在细胞提取物中的半衰期明显低于在pH 7.3磷酸盐缓冲液中。在所有介质中，Di PP ro化合物除了以d4TMP以外，还以d4T二磷酸（d4TDP）为主要产物释放出来。在抗病毒测定中，该化合物在野生型CEM / 0细胞中对HIV-1和2具有至少与d4T相

  DOI：

  10.1002/cmdc.201300500

文献信息

• Anti-HIV-Active Nucleoside Triphosphate Prodrugs
  作者：Xiao Jia、Dominique Schols、Chris Meier

  DOI：10.1021/acs.jmedchem.0c00271

  日期：2020.6.11

  We disclose a study on nucleoside triphosphate (NTP) analogues in which the γ-phosphate is covalently modified by two different biodegradable masking units and d4T as nucleoside analogue that enable the delivery of d4TTP with high selectivity in phosphate buffer (pH 7.3) and by enzyme-triggered reactions in human CD4+ T-lymphocyte CEM cell extracts. This allows the bypass of all steps normally needed

  我们公开了一项关于核苷三磷酸酯（NTP）类似物的研究，其中γ-磷酸酯被两个不同的可生物降解的掩蔽单元和D4T进行了共价修饰，从而使D4TTP在磷酸盐缓冲液（pH 7.3）和酶中具有较高的选择性CD4 + T淋巴细胞CEM细胞提取物中触发的反应。这允许绕过细胞内磷酸化通常所需的所有步骤。这些Tri PPP将包含酰氧基苄基（AB；酯）或烷氧基羰氧基苄基（ACB；碳酸酯）与ACB部分结合的环核苷酸描述为NTP递送系统。这两个不同基团的引入导致通过化学水解，特别是通过细胞提取酶选择性地形成γ-（ACB）-D4TTP。γ-（AB）-D4TTP的裂解速度比γ-（ACB）-D4TTP更快。在抗病毒测定中，这些化合物在野生型CEM / O细胞中具有更强的抗HIV-1和HIV-2活性，更重要的是在缺乏胸苷激酶的CD4 + T细胞（CEM / TK –）中具有很高的活性。
• Photocaged and Mixed Photocaged Bioreversible‐Protected ATP Derivatives as Tools for the Controlled Release of ATP
  作者：Nils Jeschik、Tobias Schneider、Chris Meier

  DOI：10.1002/ejoc.202001229

  日期：2020.11.22

  For a better understanding of ATP‐depending extra‐ and intracellular processes, a series of new chemical tools for the potential investigation of such processes was developed. We synthesized ATP derivatives with either two photocleavable masks or one photocleavable and one bio‐removable mask. The quantitative release of ATP from these compounds was proven by photolysis and by esterase incubation using

  为了更好地了解依赖ATP的细胞外和细胞内过程，开发了一系列新的化学工具来研究此类过程。我们用两个可光裂解的掩模或一个可光裂解和一个可生物去除的掩模合成了ATP衍生物。从这些化合物中定量释放的ATP已通过光解和使用HPLC监测的酯酶温育进行了证明。
• A Tri<i>PPP</i>ro‐Nucleotide Reporter with Optimized Cell‐Permeable Dyes for Metabolic Labeling of Cellular and Viral DNA in Living Cells
  作者：Vincente T. Sterrenberg、Dörte Stalling、J. Iven H. Knaack、Timothy K. Soh、Jens B. Bosse、Chris Meier

  DOI：10.1002/anie.202308271

  日期：2023.9.18

  The metabolic labeling of nucleic acids in living cells is highly desirable to track the dynamics of nucleic acid metabolism in real‐time and has the potential to provide novel insights into cellular biology as well as pathogen‐host interactions. Catalyst‐free inverse electron demand Diels–Alder reactions (iEDDA) with nucleosides carrying highly reactive moieties such as axial 2‐trans‐cyclooctene (2TCOa) would be an ideal tool to allow intracellular labeling of DNA. However, cellular kinase phosphorylation of the modified nucleosides is needed after cellular uptake as triphosphates are not membrane permeable. Unfortunately, the narrow substrate window of most endogenous kinases limits the use of highly reactive moieties. Here, we apply our TriPPPro (triphosphate pronucleotide) approach to directly deliver a highly reactive 2TCOa‐modified 2′‐deoxycytidine triphosphate reporter into living cells. We show that this nucleoside triphosphate is metabolically incorporated into de novo synthesized cellular and viral DNA and can be labeled with highly reactive and cell‐permeable fluorescent dye‐tetrazine conjugates via iEDDA to visualize DNA in living cells directly. Thus, we present the first comprehensive method for live‐cell imaging of cellular and viral nucleic acids using a two‐step labeling approach.

  摘要 对活细胞中的核酸进行代谢标记非常有助于实时跟踪核酸代谢的动态，并有可能为细胞生物学以及病原体与宿主之间的相互作用提供新的见解。与携带高活性分子（如轴向 2-反式环辛烯（2TCOa））的核苷进行的无催化剂反电子需求 Diels-Alder 反应（iEDDA）是实现 DNA 细胞内标记的理想工具。然而，由于三磷酸盐不具有膜渗透性，因此细胞摄取后需要细胞激酶对修饰的核苷进行磷酸化。遗憾的是，大多数内源性激酶的底物窗口狭窄，限制了高活性分子的使用。在这里，我们采用 TriPPPro（三磷酸代核苷酸）方法将高活性的 2TCOa 修饰的 2′-脱氧胞苷三磷酸报告物直接输送到活细胞中。我们的研究表明，这种三磷酸核苷可通过新陈代谢结合到新合成的细胞和病毒 DNA 中，并可通过 iEDDA 用高活性和细胞渗透性荧光染料-四嗪共轭物进行标记，从而直接观察活细胞中的 DNA。因此，我们首次提出了利用两步标记法对细胞和病毒核酸进行活细胞成像的综合方法。
• 5-FLUOROURACIL DERIVATIVES AS PRODRUGS FOR CANCER TREATMENT
  申请人：Universität Hamburg

  公开号：EP4151646A1

  公开（公告）日：2023-03-22

  The invention provides novel 5-Fluorouracil derivatives that are useful as prodrugs for cancer treatment. 5-Fluorouracil nucleoside triphosphates are masked at the terminal phosphate of the triphosphate group with residues that are cleaved off within the cell releasing the corresponding 5-Fluorouracil nucleoside triphosphate from the prodrug. In contrast to the classical prodrug 5-Fluorouracil, the 5-Fluorouracil derivatives of the invention need no further molecules (ribose, phosphate groups) to be added in the cell in order to become an active drug.

  本发明提供了一种新型的5-氟尿嘧啶衍生物，这些衍生物可以用作癌症治疗的前药。这些5-氟尿嘧啶核苷三磷酸化合物在三磷酸基团的末端磷酸处被掩蔽，掩蔽的基团在细胞内被剪切，从而从原药中释放出相应的5-氟尿嘧啶核苷三磷酸。与传统的5-氟尿嘧啶前药不同，本发明的5-氟尿嘧啶衍生物无需在细胞内添加额外的分子（如核糖、磷酸基团）即可成为具有活性的药物。