5-氟-1,3-二(羟甲基)嘧啶-2,4-二酮 | 74179-14-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 5-氟-1,3-二(羟甲基)嘧啶-2,4-二酮
• 英文名称: N¹,N³-bis(hydroxymethyl)-5-fluorouracil
• 英文别名: N,N'-1,3-bis(hydroxymethyl-5-fluorouracil)；1,3-bis(hydroxymethyl)-5-fluorouracil；3-bis(hydroxymethyl)-5-fluorouracil；1,3-dihydroxymethyl-5-fluorouracil；1,3-dimethylol-5-fluorouracil；bis(hydroxymethyl)-5-fluorouracil；5-Fluoro-1,3-bis(hydroxymethyl)pyrimidine-2,4(1H,3H)-dione；5-fluoro-1,3-bis(hydroxymethyl)pyrimidine-2,4-dione
• CAS: 74179-14-9
• 化学式: C₆H₇FN₂O₄
• 分子量: 190.131
• InChiKey: RKLBAAQBRHDGOA-UHFFFAOYSA-N

物化性质

• 沸点：
  315.1±52.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  81.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-氟-1,3-二(羟甲基)嘧啶-2,4-二酮 在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 succinic acid mono[(5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)methyl] ester
  参考文献：
  名称：

  Selective bone targeting 5-fluorouracil prodrugs: Synthesis and preliminary biological evaluation

  摘要：

  Bone tumor is a notoriously difficult disease to manage, requiring frequent and heavy doses of systemically administered chemotherapy. Targeting anticancer drug to the bone after systemic administration may provide both greater efficacy of treatment and less frequent administration. In this paper, a series of bone targeting Asp oligopeptides 5-fluorouracil conjugates have been synthesized in a convergent approach and well characterized by NMR and MS techniques. Their hydroxyapatite (HAP) affinity, drug release and cytotoxicity characteristics were evaluated in in vitro conditions. All the prodrugs were water soluble and exhibited high affinity to HAP. The efficient release of the active drug moiety occurring by the cleavage of different linkage in physiological conditions significantly reduced the number of viable human cancer cells. From in vivo distribution, we get these compounds with high bone-selectivity and long halflife. These results provided an effective entry to the development of new bone targeting chemotherapeutic drugs. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.05.004
• 作为产物：
  描述：

  聚合甲醛 、 5-氟脲嘧啶 以 水 为溶剂， 反应 0.25h， 生成 5-氟-1,3-二(羟甲基)嘧啶-2,4-二酮
  参考文献：
  名称：

  苄氧羰基氧甲基部分在 5-氟尿嘧啶保护基上的应用。尿嘧啶环酰胺氮的选择性烷基化

  摘要：

  描述了使用苄氧羰基氧甲基部分作为尿嘧啶环的酰胺氮保护基团的 5-氟尿嘧啶的选择性烷基化。以高产率进行保护、烷基化和脱保护。

  DOI：

  10.1246/cl.1988.1381

文献信息

• SELF-ASSEMBLY OF THERAPEUTIC AGENT-PEPTIDE NANOSTRUCTURES
  申请人：Ohio State Innovation Foundation

  公开号：US20140155577A1

  公开（公告）日：2014-06-05

  Disclosed are conjugates of hydrophobic drugs linked to protected or unprotected amino acids or peptides. The disclosed conjugates are amphiphilic and can self assemble into nanotubes. Nanotubes comprising the conjugates are also described and can have high loading of the drug and protect it from degradation or elimination. The nanotubes are well suited to deliver hydrophobic and unstable drugs to individuals.

  揭示了与受保护或未受保护的氨基酸或肽连接的疏水药物的共轭物。所述的共轭物是两性的，可以自组装成纳米管。还描述了包含这些共轭物的纳米管，可以具有高药物载荷并保护药物免受降解或排泄。这些纳米管非常适合向个体输送疏水和不稳定的药物。
• Treatment of genitourinary tract disorders
  申请人：——

  公开号：US20030170286A1

  公开（公告）日：2003-09-11

  Genitourinary system disorders are treated with therapeutic agents, and optionally further with radiation treatments.

  生殖泌尿系统疾病可以用治疗性药物进行治疗，必要时还可以进一步进行放射治疗。
• A facile method for synthesis of N-acyloxymethyl-5-fluorouracils, as a class of antitumor agents.
  作者：SUHAIL AHMAD、SHOICHIRO OZAKI、TOSHIO NAGASE、MASAAKI IIGO、REIKO TOKUZEN、AKIO HOSHI

  DOI：10.1248/cpb.35.4137

  日期：——

  Antitumor-active derivatives of 5-fluorouracil were prepared via a new method by introducing an acyloxymethyl group at the 1-, 3-, or 1, 3-position (s). These derivatives were obtained by condensing 1, 3-bis (hydroxymethyl) -5-fluorouracil with various short-/long-chain carboxylic acids or their derivatives, in the presence of dicyclohexylcarbodiimide and a catalytic amount of N, N-dimethylaminopyridine. Some of the derivatives showed strong antitumor activity against the leukemia L1210 system when administered orally.

  通过一种新方法，制备了5-氟尿嘧啶的抗肿瘤活性衍生物，方法是在1位、3位或1、3位引入酰氧基甲基基团。这些衍生物是通过将1,3-双(羟甲基)-5-氟尿嘧啶与各种短链/长链羧酸或其衍生物在二环己基碳二亚胺和催化量的N,N-二甲基氨基吡啶存在下进行缩合反应而获得的。一些衍生物在口服给药时对白血病L1210体系显示出强烈的抗肿瘤活性。
• N-hydroxymethyl Derivatives of Nitrogen Heterocycles as Possible Prodrugs I: N-hydroxymethylation of Uracils
  作者：Padam C. Bansal、Ian H. Pitman、Josiah N.S. Tam、Mathias Mertes、James J. Kaminski

  DOI：10.1002/jps.2600700803

  日期：1981.8

  constants for formation of N-1-hydroxymethyl derivatives were approximately twice those for formation of N-3-hydroxymethyl derivatives, and they were formed more rapidly throughout the pH 3--8 range. Substituents at C-5 of uracil had little effect on the thermodynamics of N-hydroxymethylation. The potential usefulness of N-hydroxymethyl compounds as prodrugs is discussed.

  制备了1，3-二羟甲基尿嘧啶，3-羟甲基-1-甲基尿嘧啶和1-羟甲基-3-甲基尿嘧啶的固体样品，并通过光谱分析确认了它们的结构。还研究了在甲醛水溶液中形成N-羟甲基化尿嘧啶的热力学和动力学。用于形成N-1-羟甲基衍生物的平衡常数大约是用于形成N-3-羟甲基衍生物的平衡常数的两倍，并且它们在整个pH 3--8范围内的形成速度更快。尿嘧啶C-5处的取代基对N-羟甲基化的热力学影响很小。讨论了N-羟甲基化合物作为前药的潜在用途。
• 5-Fluorouracil derivatives. XII. Synthesis and antitumor activity of .ALPHA.-alkylthiomethyl-, .ALPHA.-alkylsulfinylmethyl-, .ALPHA.-alkylsulfonylmethyl-, and .ALPHA.-acylthiomethyl-5-fluorouracils.
  作者：SHOICHIRO OZAKI、TOSHIO NAGASE、HIROFUMI TAMAI、HARUKI MORI、AKIO HOSHI、MASAAKI IIGO

  DOI：10.1248/cpb.35.3894

  日期：——

  For the purpose of diminishing the toxicity of 5-fluorouracil (1) and obtaining biologically active derivatives of 1 suitable for oral administration, alkylthiomethyl, alkylsulfinylmethyl, alkylsulfonylmethyl, and acylthiomethyl groups were introduced at the 1- and 3-positions of 1. The antitumor activity of these synthetic compounds was tested against L1210 leukemia in mice. 1-Alkylthiomethyl-5-fluorouracils showed weak antitumor activity at a high dose (300 mg/kg).

  为了降低 5-氟尿嘧啶（1）的毒性并获得适合口服的具有生物活性的 1-氟尿嘧啶衍生物，在 1-氟尿嘧啶的 1-和 3-位上引入了烷硫甲基、烷基亚磺酰甲基、烷基亚磺酰甲基和酰硫甲基基团。在高剂量（300 毫克/千克）下，1-烷基硫甲基-5-氟尿嘧啶显示出微弱的抗肿瘤活性。