1-hexanoyloxymethyl-5-fluorouracil | 66542-38-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-hexanoyloxymethyl-5-fluorouracil
• 英文别名: 5-fluoro-1-hexanoyloxymethyl-1H-pyrimidine-2,4-dione；1-Caproyloxymethyl-5-fluor-uracil；1-Caproyloxymethyl-5-fluorouracil；(5-fluoro-2,4-dioxopyrimidin-1-yl)methyl hexanoate
• CAS: 66542-38-9
• 化学式: C₁₁H₁₅FN₂O₄
• 分子量: 258.25
• InChiKey: YIILCDVPWNEKAN-UHFFFAOYSA-N

物化性质

• 熔点：
  95-96 °C
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-hexanoyloxymethyl-5-fluorouracil 在 硼酸 作用下， 以 水 、 乙腈 为溶剂， 生成 5-氟-1-(羟甲基)嘧啶-2,4-二酮
  参考文献：
  名称：

  1-Alkylcarbonyloxymethyl Prodrugs of 5-Fluorouracil (5-FU): Synthesis, Physicochemical Properties, and Topical Delivery of 5-FU

  摘要：

  1-Alkylcarbonyloxymethyl (1-ACOM) prodrugs of 5-fluorouracil (5-FU) have been synthesized and characterized by their solubilities in isopropyl myristate (SIPM) and pH 4.0 buffer (SH2O), by their partition coefficients between isopropyl myristate (IPM) and pH 4.0 buffer (K) and by their abilities to deliver total 5-FU species into (Cs) and through (Ji) hairless mouse skin from an IPM vehicle. All of the prodrugs were much more lipophilic (SIPM) than 5-FU (> 60 times), and two members of the series (alkyl = C1 and C2, acetyl- and propionyloxymethyl) were also more soluble in water than 5-FU. The two more water-soluble members gave larger Ji values than the other members of the series, with C2 exhibiting the best biphasic solubility and the largest Ji value (16 times that of 5-FU). The ability of the 1-ACOM-5-FU prodrugs to deliver total 5-FU species into skin (Cs) was greater than the delivery of 5-FU by 5-FU, except for the last two members of series (alkyl = C7 and C9, octanoyl- and decanoyl-oxymethyl). However, the ratios of normalized Cs to Ji for the series was less than that exhibited by 5-FU, except for C7 and C9. Also, except for C9, significant amounts of intact prodrug as percentages of total 5-FU species were found in the receptor phases during the course of the diffusion cell experiments, ranging from 55% for C1 to 12% for C7.

  DOI：

  10.1021/js9702574
• 作为产物：
  描述：

  chloromethyl hexanoate 以 乙腈 为溶剂， 反应 25.0h， 生成 1-hexanoyloxymethyl-5-fluorouracil
  参考文献：
  名称：

  1-Alkylcarbonyloxymethyl Prodrugs of 5-Fluorouracil (5-FU): Synthesis, Physicochemical Properties, and Topical Delivery of 5-FU

  摘要：

  1-Alkylcarbonyloxymethyl (1-ACOM) prodrugs of 5-fluorouracil (5-FU) have been synthesized and characterized by their solubilities in isopropyl myristate (SIPM) and pH 4.0 buffer (SH2O), by their partition coefficients between isopropyl myristate (IPM) and pH 4.0 buffer (K) and by their abilities to deliver total 5-FU species into (Cs) and through (Ji) hairless mouse skin from an IPM vehicle. All of the prodrugs were much more lipophilic (SIPM) than 5-FU (> 60 times), and two members of the series (alkyl = C1 and C2, acetyl- and propionyloxymethyl) were also more soluble in water than 5-FU. The two more water-soluble members gave larger Ji values than the other members of the series, with C2 exhibiting the best biphasic solubility and the largest Ji value (16 times that of 5-FU). The ability of the 1-ACOM-5-FU prodrugs to deliver total 5-FU species into skin (Cs) was greater than the delivery of 5-FU by 5-FU, except for the last two members of series (alkyl = C7 and C9, octanoyl- and decanoyl-oxymethyl). However, the ratios of normalized Cs to Ji for the series was less than that exhibited by 5-FU, except for C7 and C9. Also, except for C9, significant amounts of intact prodrug as percentages of total 5-FU species were found in the receptor phases during the course of the diffusion cell experiments, ranging from 55% for C1 to 12% for C7.

  DOI：

  10.1021/js9702574

文献信息

• 5-Fluorouracil derivatives. IV. Synthesis of antitumor-active acyloxyalkyl-5-fluorouracils.
  作者：SHOICHIRO OZAKI、YUTAKA WATANABE、TOMONORI HOSHIKO、HARUO MIZUNO、KATSUTOSHI ISHIKAWA、HARUKI MORI

  DOI：10.1248/cpb.32.733

  日期：——

  The toxicity and tumor affinity of 5-fluorouracil (1) have been modified by the introduction of acyloxyalkyl group (s) at the 1-, 3- or 1, 3-position (s) of 1. 1-Acyloxyalkyl-5-fluorouracil (3), 3-acyloxyalkyl-5-fluorouracil (4) and 1, 3-bis (acyloxyalkyl)-5-fluorouracil (5) were obtained by three methods : i) the reaction of α-chloroalkyl carboxylate (2) with 1, ii) the reaction of alkylidene diacylate with 2, 4-bis (trimethylsilyloxy)-5-fluoropyrimidine, iii) partial hydrolysis of 5. Compounds 3, 4 and 5 showed antitumor activity.

  通过在 5-氟尿嘧啶（1）的 1-、3-或 1，3-位（s）上引入酰氧基烷基（s），5-氟尿嘧啶（1）的毒性和肿瘤亲和力得到了改变。1-Acyloxyalkyl-5-fluorouracil (3)、3-acyloxyalkyl-5-fluorouracil (4) 和 1，3-bis (acyloxyalkyl)-5-fluorouracil (5) 是通过以下三种方法获得的：i) α-Cloroalkyl carboxylate (2) 与 1 的反应；ii) 亚烷基二乙酸酯与 2，4-bis (trimethylsilyloxy)-5-fluoropyrimidine 的反应；iii) 5 的部分水解。化合物 3、4 和 5 具有抗肿瘤活性。
• 靶向MCT1转运体的5-氟尿嘧啶成酯前药
  申请人：沈阳药科大学

  公开号：CN109761915B

  公开（公告）日：2021-12-21

  本发明属于医药领域，涉及靶向MCT1转运体的5‑氟尿嘧啶成酯前药，具体涉及包括不同碳链长度的含有单羧酸酯的5‑氟尿嘧啶口服前药的合成，以及其在药物传递和治疗中的应用。本发明设计合成了不同碳链长度含有单羧酸酯的5‑氟尿嘧啶口服前药，将该前药用于靶向MCT1转运体，从而实现稳定性好、毒副作用低、渗透性高和口服生物利用度高的效果。同时，以不含羧酸的成酯前药作为对照，考察含有或不含有单羧酸的前药在化学性质以及体内外实验等方面的差异，以及前药是否能通过靶向MCT1转运体进而改善原有5‑氟尿嘧啶渗透性差以及口服生物利用度低的缺点。得到了最佳的口服前药，满足临床中对口服制剂的迫切需求。
• Uracil derivatives
  申请人：Mitsui Toatsu Chemicals, Incorporated

  公开号：US04267326A1

  公开（公告）日：1981-05-12

  New uracil derivatives of the general formula: ##STR1## wherein R.sup.1 stands for a hydrogen atom or a grouping of the formula: ##STR2## R.sup.2 for a hydrogen atom, an alkyl group or a phenyl group and R.sup.3 for an alkyl group or a phenyl group, with the proviso that when both R.sup.1 and R.sup.2 stand for a hydrogen atom, R.sup.3 stands for a phenyl group or a straight chain alkyl group with 3.about.11 carbon atoms, that when R.sup.1 stands for a hydrogen atom and R.sup.2 for methyl group, R.sup.3 stands for an alkyl group with at least 2 carbon atoms or a phenyl group, and that when R.sup.1 stands for a hydrogen atom and R.sup.3 for methyl group, R.sup.2 stands for an alkyl group with at least 2 carbon atoms or a phenyl group. These uracil derivatives are prepared by reacting 5-fluorouracil with an .alpha.-haloalkyl carboxylate or with an aldehyde diacylate or by hydrolyzing a 1,3-bis(acyloxymethyl)-5-fluorouracil with an acid or alkali. These uracil derivatives are useful as improved anti-tumor agents especially for oral administration and injection.

  新的尿嘧啶衍生物的一般式为：##STR1## 其中 R.sup.1 代表氢原子或公式的基团：##STR2## R.sup.2 代表氢原子、烷基或苯基，R.sup.3 代表烷基或苯基，但当 R.sup.1 和 R.sup.2 都代表氢原子时，R.sup.3 代表苯基或具有 3~11 个碳原子的直链烷基；当 R.sup.1 代表氢原子，R.sup.2 代表甲基基团时，R.sup.3 代表至少具有 2 个碳原子的烷基或苯基；当 R.sup.1 代表氢原子，R.sup.3 代表甲基基团时，R.sup.2 代表至少具有 2 个碳原子的烷基或苯基。这些尿嘧啶衍生物是通过将 5-氟尿嘧啶与α-卤代烷基羧酸酯或醛二酰酸酯反应或通过酸或碱水解 1,3-双(酰氧甲基)-5-氟尿嘧啶制备的。这些尿嘧啶衍生物可用作改进的抗肿瘤剂，特别适用于口服和注射。
• OZAKI, SHOICHIRO;IKE, YOSHIMASA;ISHIKAWA, KATSUTOSHI;MORI, HARUKI
  作者：OZAKI, SHOICHIRO、IKE, YOSHIMASA、ISHIKAWA, KATSUTOSHI、MORI, HARUKI

  DOI：——

  日期：——
• OZAKI, SHOICHIRO;WATANABE, YUTAKA;HOSHIKO, TOMONORI;MIZUNO, HARUO;ISHIKAW+, CHEM. AND PHARM. BULL., 1984, 32, N 2, 733-738
  作者：OZAKI, SHOICHIRO、WATANABE, YUTAKA、HOSHIKO, TOMONORI、MIZUNO, HARUO、ISHIKAW+

  DOI：——

  日期：——