5'-palmitoyl-5-fluorouridine | 118408-87-0

• 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: 5'-palmitoyl-5-fluorouridine
• 英文别名: 5'-O-palmitoyl-5-fluorouridine；[(2R,3S,4R,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl hexadecanoate
• CAS: 118408-87-0
• 化学式: C₂₅H₄₁FN₂O₇
• 分子量: 500.608
• InChiKey: TZOQCUBRDHGDPZ-VDEHWKIFSA-N

物化性质

• 熔点：
  165-166 °C
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  35
• 可旋转键数：
  18
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-氟-2',3'-异亚丙基尿苷 在 三氟乙酸 作用下， 以 吡啶 为溶剂， 反应 3.0h， 生成 5'-palmitoyl-5-fluorouridine
  参考文献：
  名称：

  Antitumoral Activity of Liposomes and Immunoliposomes Containing 5-Fluorouridine Prodrugs

  摘要：

  Liposomes and immunoliposomes containing cytotoxic agents may be highly efficacious in intracavity therapy of malignancies confined principally to the peritoneal cavity. To assess the feasibility of this locoregional treatment, we prepared two derivatives of 5-fluorouridine (5-FUR), a highly cytotoxic metabolite of 5-fluorouracile, and incorporated them into REV liposomes, prepared with the reverse phase evaporation method. Encapsulation efficiency, drug leakage, and stability were determined, and size analysis and differential scanning calorimetry were carried out to evaluate the drug delivery potential of liposomes containing 5'-palmitoyl-5-FUR, 5'-succinyl-5-FUR, or the parent drug 5-FUR, The most suitable drug for encapsulation, in terms of minimum leakage and encapsulation efficiency, was 5'-palmitoyl-5-FUR, which differential scanning calorimetry indicated as being firmly anchored to the lipid bilayer. Thus, 5'-palmitoyl-5-FUR was chosen to prepare a chemotherapeutic liposome-monoclonal antibody conjugate (immunoliposome). The covalent linkage between antibody and liposome was realized by coupling the thiolated monoclonal antibody AR-3 with REV liposomes, containing N[4-(p-maleimidophenyl)butyryl]phosphatidylethanolamine. The cytotoxic activity of drug-bearing liposomes and immunoliposomes was evaluated on the HT-29 human colon adenocarcinoma cell line; the immunoliposomes had higher cytotoxicity than liposomes or 5-FUR. To explore the potential of these drug formulations in anticancer therapy, we ip injected liposomes or immunoliposomes into athymic mice ip grafted with human HT-29 cell line, in this mouse model, the immunoliposome containing 5'-palmitoyl-5-FUR displayed the best antitumoral activity, since on day 27 postgraft only 5% of residual tumor mass was present, compared to control mice: there was a close relationship between exposure time of tumor tissue to the drug and antitumor potency.

  DOI：

  10.1021/js9604467

文献信息

• 5-Fluorouracil derivatives. XVII. Synthesis and antitumor activity of 5'-O-acyl-5-fluorouridines.
  作者：Shoichiro OZAKI、Takahiko AKIYAMA、Yoshimasa IKE、Haruki MORI、Akio HOSHI

  DOI：10.1248/cpb.37.3405

  日期：——

  With the aim of diminishing the toxicity of 5-fluorouridine (1) and obtaining biologically active derivatives of 1, various kinds of 5'-O-acyl-8-fluorouridines 2 were synthesized. The antitumor activity of the compounds against L-1210 leukemia in mice was examined. The 5'-O-heptanoyl derivative 2h showed the highest antitumor activity.

  为了降低 5-氟尿苷（1）的毒性并获得 1 的生物活性衍生物，合成了各种 5'-O-acyl-8-fluorouridines 2。研究了这些化合物对小鼠 L-1210 白血病的抗肿瘤活性。5'-O-庚酰基衍生物 2h 的抗肿瘤活性最高。
• Diacylnucleosides and process for preparing the same
  申请人：Asahi Kasei Kogyo Kabushiki Kaisha

  公开号：US04097665A1

  公开（公告）日：1978-06-27

  Compounds represented by formula (I) ##STR1## wherein one of Z.sub.1 ', Z.sub.2 ', Z.sub.3 ' and Z.sub.4 ' represents R, another one of Z.sub.1 ', Z.sub.2 ', Z.sub.3 ' and Z.sub.4 ' represents Z, and the remaining two moieties of Z.sub.1 ', Z.sub.2 ', Z.sub.3 ' and Z.sub.4 ' represents a hydrogen atom and/or a protective group, one of R and Z represents A.sub.1 and the other represents A.sub.2, A.sub.1 being an acyl group having 14 to 22 carbon atoms which does not contain a carboxylic group and A.sub.2 being an acyl group having 2 to 14 carbon atoms and having one carboxyl group, X represents a hydrogen atom or a halogen atom (hereinafter referred to as Compound Ia); a 2,2'-anhydro product of Compound Ia wherein Z.sub.2 ' represents a hydrogen atom (hereinafter referred to as Compound Ib); an arabinosylation product of Compound Ia (hereinafter referred to as Compound Ic); a deamination product of Compound Ia (hereinafter referred to as Compound Id); a 2'-deoxy product of Compound Id wherein Z.sub.2 ' represents a hydrogen atom (hereinafter referred to as Compound Ie); a salt of Compound Ia, Ib, Ic, or Id or Ie having an A.sub.2 group with a base (hereinafter referred to as Compound If); and a salt of Compound Ia, Ib or Ic wherein Z.sub.1 ' represents a hydrogen atom with an acid (hereinafter referred to as Compound Ih); and processes for preparing the same.

  化合物的化学式为（I）##STR1## 其中Z.sub.1'，Z.sub.2'，Z.sub.3'和Z.sub.4'中的一个代表R，Z.sub.1'，Z.sub.2'，Z.sub.3'和Z.sub.4'中的另一个代表Z，Z.sub.1'，Z.sub.2'，Z.sub.3'和Z.sub.4'的剩余两个基团代表氢原子和/或保护基，R和Z中的一个代表A.sub.1，另一个代表A.sub.2，其中A.sub.1是具有14至22个碳原子且不含羧基的酰基，A.sub.2是具有2至14个碳原子且具有一个羧基的酰基，X代表氢原子或卤素原子（以下简称化合物Ia）; 化合物Ia的2,2'-去水产物，其中Z.sub.2'代表氢原子（以下简称化合物Ib）; 化合物Ia的阿拉伯糖基化产物（以下简称化合物Ic）; 化合物Ia的脱氨产物（以下简称化合物Id）; 化合物Id的2'-去氧产物，其中Z.sub.2'代表氢原子（以下简称化合物Ie）; 具有碱的A.sub.2基团的化合物Ia，Ib，Ic，或Id或Ie的盐（以下简称化合物If）; 以及具有酸的化合物Ia，Ib或Ic的Z.sub.1'代表氢原子的盐（以下简称化合物Ih）; 以及制备它们的过程。
• OZAKI, SHOICHIRO;AKIYAMA, TAKAHIKO;IKE, YOSHIMASA;MORI, HARUKI;HOSHI, AKI+, CHEM. AND PHARM. BULL., 37,(1989) N2, C. 3405-3408
  作者：OZAKI, SHOICHIRO、AKIYAMA, TAKAHIKO、IKE, YOSHIMASA、MORI, HARUKI、HOSHI, AKI+

  DOI：——

  日期：——
• 5-FLUOROURIDINE DERIVATIVES
  申请人：B. Braun Melsungen AG

  公开号：EP2900679B1

  公开（公告）日：2020-07-01
• US4097665A
  申请人：——

  公开号：US4097665A

  公开（公告）日：1978-06-27