5-氟-1-(2-羟基乙氧基甲基)嘧啶-2,4-二酮 | 77474-50-1

• 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-(2-羟基乙氧基甲基)嘧啶-2,4-二酮
• 英文名称: 1-(2-hydroxyethoxy)methyl-5-fluorouracil
• 英文别名: 1-<(2-hydroxyethoxy)methyl>-5-fluorouracil；5-fluoro-1-<(2-hydroxyethoxy)methyl>uracil；1-(2-hydroxyethoxymethylene)-5-fluorouracil；5-fluoro-1-(2'-hydroxyethoxymethyl)uracil；5-fluoroacyclouridine；5-fluoro-1-[(2-hydroxyethoxy)methyl]uridine；5-Fluoro-1-((2-hydroxyethoxy)methyl)uracil；5-fluoro-1-(2-hydroxyethoxymethyl)pyrimidine-2,4-dione
• CAS: 77474-50-1
• 化学式: C₇H₉FN₂O₄
• 分子量: 204.158
• InChiKey: NIXARNBYNBFWPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  5-氟-1-(2-羟基乙氧基甲基)嘧啶-2,4-二酮 在 咪唑 、 lithium diisopropyl amide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 1-<<2-<(tert-butyldimethylsilyl)oxy>ethoxy>methyl>-6-(phenylselenenyl)-5-fluorouracil
  参考文献：
  名称：

  Activity of acyclic 6-(phenylselenenyl)pyrimidine nucleosides against human immunodeficiency viruses in primary lymphocytes

  摘要：

  Several 6-phenylselenenyl-substituted acyclouridine derivatives were prepared for evaluation as antiviral agents. Lithiation of the tert-butyldimethylsilyl-protected acyclonucleosides 4a-f with lithium diisopropylamide at -78-degrees-C, followed by reaction with diphenyl diselenide as an electrophile, and subsequent removal of the protecting group with tetra n-butylammonium fluoride gave 1-[(2-hydroxyethoxy)methyl]-6-(phenylselenenyl)uracils 6a-f in 50-70% overall yield. The potency and spectrum of activity of compounds 6a-f against HIV-1 in vitro was similar to HEPT (1), a related 6-phenylthio acyclonucleoside. However, whereas HEPT inhibited HIV-1 reverse transcriptase, the selenium-containing derivatives were ineffective, suggesting a different mechanism of action. Of significance was the finding that the 6-phenylselenenyl acyclonucleosides inhibited also HIV-2 in primary human lymphocytes.

  DOI：

  10.1021/jm00115a022
• 作为产物：
  描述：

  2-[(5-氟-2,4-二氧代-3,4-二氢-1(2H)-嘧啶基)甲氧基]乙基乙酸酯 在 sodium 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以96%的产率得到5-氟-1-(2-羟基乙氧基甲基)嘧啶-2,4-二酮
  参考文献：
  名称：

  Nucleic acid related compounds. 37. Convenient and high-yield syntheses of N-[(2-hydroxyethoxy)methyl] heterocycles as "acyclic nucleoside" analogues

  摘要：

  1,3-二氧杂环戊烷与乙酰溴反应，得到（2-乙酰氧乙氧基）溴甲烷（2a），收率为88%。多种嘧啶和三种氯代嘌呤经过三甲基硅基化处理后与2a偶联。相应的N-1和N-9烷基化产物（收率为79-89%）经去乙酰化处理后得到N-[(2-羟基乙氧基)甲基]杂环化合物。2-氨基-6-取代嘌呤衍生物的6-氨基或6-氯取代基经过腺苷脱氨酶顺利水解，得到9-[(2-羟基乙氧基)甲基]鸟苷（无环鸟苷），这是一种有效的抗病毒药物。

  DOI：

  10.1139/v82-081

文献信息

• Synthesis of pyrimidine acyclonucleosides
  作者：H. M. Abrams、L. Ho、S. H. Chu

  DOI：10.1002/jhet.5570180520

  日期：1981.8

  Nucleoside analogues of uridine, 5-bromo-, 5-iodo-, and 5-fluorouridines, thymidine and cytidine were prepared by condensing appropriately substituted 2,4-dimethoxypyrimidines with an acyclic side chain in the form of a benzoylated halo-ether, and subsequent removal of the protecting benzoyl group in base. The 2′-O-p-tosylates of these nucleoside analogues could then be modified to 2′-halo-, azido-

  尿苷，5-溴-，5-碘-和5-氟尿苷，胸苷和胞苷的核苷类似物是通过将适当取代的2,4-二甲氧基嘧啶与无环侧链缩合成苯甲酰化卤代醚的形式制备的，随后除去碱中的保护性苯甲酰基。2'- ø - p这些核苷类似物-tosylates然后可以修改成2'-卤代- ，叠氮基，和氨基衍生物。这些化合物中的许多是体外尿苷磷酸化酶的竞争性抑制剂，最活跃的是5-甲基-1-（2'-羟基乙氧基甲基）尿嘧啶。
• Bisphosphonate conjugates and methods of making and using the same
  申请人：——

  公开号：US20020142994A1

  公开（公告）日：2002-10-03

  The present invention is directed to particular bisphosphonate compounds, and in particular, to bisphosphonate conjugates that are useful in the treatment of soft tissues surrounding bone and bone-related diseases, such as bone cancer and osteoporosis.

  本发明涉及特定的双膦酸盐化合物，特别是用于治疗围绕骨骼的软组织和与骨骼相关疾病，如骨癌和骨质疏松症的双膦酸盐化合物。
• A facile synthetic method for pyrimidine acyclonucleoside derivatives.
  作者：KIYOSHIGE OCHI、KATSUHITO MIYAMOTO、YUTAKA MIURA、HIROKI MITSUI、ISAO MATSUNAGA、MINORU SHINDO

  DOI：10.1248/cpb.33.1703

  日期：——

  A facile synthetic method for pyrimidine acyclonucleosides is described. Bis (trimethylsilyl) ethers of uracils (1-3) react with 2-substituted 1, 3-dioxolanes (4) in the presence of a Lewis acid to form 1-[α-(2-hydroxyethoxy) alkyl] uracil derivatives. Treatment of these reaction mixtures with methanol containing sodium hydrogen carbonate or aqueous sodium hydroxide gives pyrimidine acyclonucleosides (5a-g).

  描述了一种简单的合成嘧啶非环核苷的方法。尿嘧啶的二（三甲基硅基）醚（1-3）在路易斯酸的存在下与2-取代的1,3-二氧戊烷（4）反应，形成1-[α-(2-羟基乙氧基)烷基]尿嘧啶衍生物。将这些反应混合物用含有碳酸氢钠的甲醇或水合氢氧化钠处理，得到嘧啶非环核苷（5a-g）。
• Novel uracil derivatives, process for preparing the same and a
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US04415573A1

  公开（公告）日：1983-11-15

  Novel uracil derivatives of the formula ##STR1## (wherein R.sub.1, R.sub.2 R.sub.3 and X are defined in the description) and their pharmaceutically acceptable salts, process for preparing the same and pharmaceutical composition containing the same are disclosed. The uracil derivatives have good antitumor activity and, therefore, are useful as antitumor preparation.

  公开了一种新型尿嘧啶衍生物的化学式 ##STR1##（其中R.sub.1、R.sub.2、R.sub.3和X在描述中有定义）及其药学上可接受的盐，制备这种衍生物的方法以及含有这种衍生物的药物组合物。这些尿嘧啶衍生物具有良好的抗肿瘤活性，因此可用作抗肿瘤制剂。
• Synthesis and antitumor activity of an acyclonucleoside derivative of 5-fluorouracil
  作者：Andre Rosowsky、Sun-Hyuk Kim、Michael Wick

  DOI：10.1021/jm00142a011

  日期：1981.10

  The pyrimidine acyclonucleoside 5-fluoro-1-[(2-hydroxyethoxy)methyl]uracil (3) was synthesized as part of a program aimed at the development of new 5-fluorouracil derivatives with fewer side effects and a broader margin of safety. Condensation of 5-fluoro-2,4-bis[(trimethylsilyl)oxy]pyrimidine with 2-acetoxyethyl acetoxymethyl ether (6) in the presence of SnCl4 afforded the acetate ester 7, which on

  嘧啶无环核苷5-氟-1-[（2-羟基乙氧基）甲基]尿嘧啶（3）的合成是该计划的一部分，该计划旨在开发新的5-氟尿嘧啶衍生物，具有较少的副作用和较宽的安全范围。在SnCl4存在下，5-氟-2,4-双[（三甲基甲硅烷基）氧基]嘧啶与2-乙酰氧基乙基乙酰氧基甲基醚（6）的缩合反应得到乙酸酯7，在用NaOMe脱保护后得到50-60％的3总产量。类似地分别获得了5-溴和5-碘类似物10和11。5-氟-4-（甲硫基）-2-[（三甲基甲硅烷基）氧基]嘧啶与2-乙酰氧基乙基乙酰氧基甲基醚和SnCl4的反应，然后进行氨解，得到5-氟-1-[（2-羟基乙氧基）甲基]胞嘧啶（12）。用亚硝酸将12脱氨基产生3，从而证实5-氟-2的烷基化，在N1出现了4-双[（三甲基甲硅烷基）氧基]嘧啶。3种针对L1210小鼠白血病细胞的ID50为1.7 x 10（-5）M，而FU为1 x 10（-6）M。5-氟胞嘧啶类似物12在最高1