β-5-Fluor-3'-acetyl-2'-desoxy-uridin | 2059-38-3

• 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: β-5-Fluor-3'-acetyl-2'-desoxy-uridin
• 英文别名: O^3'-acetyl-5-fluoro-2'-deoxy-uridine；[(2R,3S,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-2-(hydroxymethyl)oxolan-3-yl] acetate
• CAS: 2059-38-3
• 化学式: C₁₁H₁₃FN₂O₆
• 分子量: 288.232
• InChiKey: PRIOYEZNDKYFSU-DJLDLDEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  β-5-Fluor-3'-acetyl-2'-desoxy-uridin 在 ammonium hydroxide 、 水 、 三氯氧磷 作用下， 生成 3'-O-Acetyl-5-fluoro-2'-deoxyuridine-5'-monophosphate
  参考文献：
  名称：

  Nucleoside conjugates. 8. The preparation of 5-fluoro-2′-deoxyuridine conjugates of corticosteroids

  摘要：

  Three 5'-(steroid-21-phosphoryl)-5-fluoro-2'-deoxyuridines (VI-VIII) have been prepared and characterized by uv, ir, 1H-nmr, elemental analysis, chemical and enzymatic hydrolyses. These new compounds are 5-fluoro-2'-deoxyuridine conjugates of cortisol (VI), cortico-sterone (VII), and prednisolone (VIII). Besides the physical and analytical data, all of the conjugates were demonstrated to be enzymatically hydrolyzed to the corresponding steroid and 5-fluoro-2'-deoxyuridine 5'-monophosphate (III), and the latter was further shown to be hydrolyzed to 5-fluoro-2'-deoxyuridine (II) by phosphodiesterase I, 5'-nucleotidase, and acid phosphatase. However, they were shown to be resistant to hydrolysis by bacterial alkaline phosphatase.

  DOI：

  10.1016/0039-128x(86)90056-5
• 作为产物：
  描述：

  5-fluoro-3'-O-acetyl-5'-O-tert-butyldimethylsilyl-2'-deoxyuridine 在 triethylamine tris(hydrogen fluoride) 作用下， 以 二氯甲烷 为溶剂， 以99 %的产率得到β-5-Fluor-3'-acetyl-2'-desoxy-uridin
  参考文献：
  名称：

  5-FLUOROURACIL DERIVATIVES AS PRODRUGS FOR CANCER TREATMENT

  摘要：

  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。

  公开号：

  EP4151646A1

文献信息

• Compounds for the protection of sulfur containing linkers in nucleic acid synthesis
  申请人：Duff Robert

  公开号：US08673885B1

  公开（公告）日：2014-03-18

  Aromatic and alkyl thiocarbonates with and without a neighboring group that participates in the hydrolysis of a thiocarbonate are described. The aromatic or alkyl thiocarbonates can be used for the protection of sulfur during oligonucleotide synthesis. Their facile processes of manufacture and methods of using the same are provided.

  描述了具有参与硫代碳酸酯水解的相邻基团的芳香族和烷基硫代碳酸酯。这些芳香族或烷基硫代碳酸酯可用于在寡核苷酸合成过程中保护硫。提供了它们的简便制造过程和使用方法。
• [EN] NITROREDUCTASE-RELEASABLE PRO-DRUGS AND METHODS FOR USING THE SAME<br/>[FR] PRO-MÉDICAMENT À LIBÉRATION PAR NITRORÉDUCTASE ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：UNIV ARIZONA

  公开号：WO2020210175A1

  公开（公告）日：2020-10-15

  The present invention provides a nitroreductase-releasable pro-drug of Formula (I); where Ar1, m, n, Z, Y, L, and A are as defined herein, and methods for using and producing the same. Compound of formula (I) is useful in oral administration of the active pharmaceutical ingredient to the distal gut region of a subject to treat a wide variety of clinical conditions associated with distal gut region of a subject, such as colorectal cancer, inflammatory bowel disease (IBD), infectious diarrhea, bacterial infections, and bacterial overgrowth.

  本发明提供了一种硝基还原酶可释放的前药，其具有式(I)的结构；其中Ar1、m、n、Z、Y、L和A如本文所定义，以及使用和生产该前药的方法。式(I)化合物可用于口服给药活性药物成分至受试者的远端肠道区域，以治疗与远端肠道区域相关的多种临床状况，例如结直肠癌、炎症性肠病（IBD）、感染性腹泻、细菌感染和细菌过度生长。
• Synthesis and Antitumor Evaluation of Bis[(pivaloyloxy)methyl] 2'-Deoxy-5-fluorouridine 5'-Monophosphate (FdUMP): A Strategy To Introduce Nucleotides into Cells
  作者：David Farquhar、Saeed Khan、Devendra N. Srivastva、Priscilla P. Saunders

  DOI：10.1021/jm00049a009

  日期：1994.11

  enter cells by passive diffusion and to revert to FdUMP after removal of the PIV groups by hydrolytic enzymes. The most convenient preparation of PIV2FdUMP was by condensation of 2'-deoxy-5-fluorouridine (FUdR) with PIV2 phosphate in the presence of triphenylphosphine and diethyl azodicarboxylate (the Mitsunobo reagent). PIV2FdUMP was stable in the pH range 1.0-4.0 (t1/2 > 100 h). It was also fairly

  合成了2'-脱氧-5-氟尿苷5'-单磷酸酯（FdUMP）的双[（新戊酰氧基）甲基] [PIV2]衍生物，作为FdUMP潜在的膜渗透性前药。该化合物设计为通过被动扩散进入细胞，并在通过水解酶去除PIV基团后还原为FdUMP。最方便的制备PIV2FdUMP的方法是在三苯基膦和偶氮二羧酸二乙酯（Mitsunobo试剂）存在下，将2'-脱氧-5-氟尿苷（FUdR）与磷酸PIV2缩合。PIV2FdUMP在1.0-4.0的pH范围内稳定（t1 / 2> 100小时）。在pH 7.4（t1 / 2 = 40.2小时）时也相当稳定。但是，在0.05 M NaOH溶液中，它迅速降解（t1 / 2 <2分钟）。在猪肝羧酸酯酶存在下，将PIV2FdUMP定量转化为单[[（新戊酰氧基）甲基] [PIV1]类似物PIV1FdUMP。孵育24小时后，仅观察到痕量的FdUMP（1-3％），表明PIV1FdUMP是羧酸酯
• Regioselective Acylation of Nucleosides Catalyzed by<i>Candida Antarctica</i>Lipase B: Enzyme Substrate Recognition
  作者：Ning Li、Min-Hua Zong、Ding Ma

  DOI：10.1002/ejoc.200800780

  日期：2008.11

  The substrate recognition of Candida antarctica lipase B (CAL-B) in the acylation of nucleosides was revealed through rational substrate engineering for the first time. CAL-B displayed lower activities and excellent 5-regioselectivities (94 to 99 %) in the acylation of ribonucleosides 1f–1j as compared to those in the acylation of 2-deoxynucleosides 1a– 1e. The excellent regioselectivities might be

  首次通过合理的底物工程揭示了南极念珠菌脂肪酶B（CAL-B）在核苷酰化中的底物识别。与 2-脱氧核苷 1a-1e 的酰化相比，CAL-B 在核糖核苷 1f-1j 的酰化中表现出较低的活性和优异的 5-区域选择性（94% 至 99%）。优异的区域选择性可能归因于存在于 2-羟基中的有利的空间位阻
• Synthesis and anticancer activities of amphiphilic 5-fluoro-2′-deoxyuridylic acid prodrugs
  作者：Peter S. Ludwig、Reto A. Schwendener、Herbert Schott

  DOI：10.1016/j.ejmech.2004.12.006

  日期：2005.5

  lyl-(3' --> 5')-3'-O-acetyl-5-fluoro-2'-deoxyuridine (dC(pam)-5-FdU(Ac), N4-palmitoyl-2',3'-dideoxycytidylyl-(5' --> 5')-3'-O-acetyl-5-fluoro-2'-deoxyuridine (ddC(pam)-(5' --> 5')-5-FdU(Ac), 5-fluoro-2'-deoxyuridylyl-(3' --> 5')-5-fluoro-N4-hexadecyl-2'-deoxycytidine (5-FdU-5-FdC(hex)), and of the new liponucleotide 1-O-octadecyl-rac-glycerylyl-(3 --> 5')-5-fluoro-2'-deoxyuridine (Oct1Gro-(3 --> 5')-5-FdU)

  5'-氟-2'-脱氧尿苷-5'-单磷酸酯（5-FdUMP）的两亲抗癌前药是通过将亲脂性胞嘧啶衍生物或磷脂与5-氟-2'-脱氧尿苷偶联的氢膦酸盐方法合成的（5 -FdU）。美国国家癌症研究所体外抗癌筛选计划内的研究表明，异二核苷磷酸酯具有很高的抗癌活性：N4-棕榈酰基-2'-脱氧胞嘧啶-（3'-> 5'）-3'-O-乙酰基-5 -氟-2'-脱氧尿苷（dC（pam）-5-FdU（Ac），N4-棕榈酰基-2'，3'-二脱氧胞嘧啶-（5'-> 5'）-3'-O-乙酰基-5 -氟-2'-脱氧尿苷（ddC（pam）-（5'-> 5'）-5-FdU（Ac），5-氟-2'-脱氧尿苷-（3'-> 5'）-5 -氟-N4-十六烷基-2'-脱氧胞苷（5-FdU-5-FdC（hex）），以及新的脂核苷酸1-O-十八烷基-rac-甘油基-（3-> 5'）-5-氟-2'-脱氧尿苷（Oct1Gro-（3-> 5'）-5