1-乙氧基甲基-5-氟尿嘧啶 | 57610-22-7

• 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: 1-乙氧基甲基-5-氟尿嘧啶
• 中文别名: 1-(乙氧基甲基)-5-氟嘧啶-2,4(1H,3H)-二酮
• 英文名称: 1-ethoxymethyl-5-fluorouracil
• 英文别名: N1-ethoxymethyl-5-fluorouracil；1-(ethoxymethyl)-5-fluoropyrimidine-2,4-dione
• CAS: 57610-22-7
• 化学式: C₇H₉FN₂O₃
• 分子量: 188.158
• InChiKey: OUAPULXYUWUOHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-乙氧基甲基-5-氟尿嘧啶 在 三乙胺 作用下， 以 1,4-二氧六环 、 氯仿 为溶剂， 反应 3.0h， 生成 乙嘧替氟
  参考文献：
  名称：

  Synthesis of 5-Fluorouracil Derivatives Containing an Inhibitor of 5-Fluorouracil Degradation.

  摘要：

  研究了 5-氟尿嘧啶（5-FUra）降解抑制剂 2，4-（2）和 2，6-二羟基吡啶（3）的反应活性。2 和 2，4-双（三甲基硅氧基）吡啶分别在 4-OH 和 2-OH 位优先与等摩尔量的酸氯发生酰化反应，通过 X 射线晶体图分析确定单苯甲酰化 5-氯-2，4-二羟基吡啶 (2b) 的结构为 4-苯甲酰基氧基-5-氯-2-吡啶酮 (5b)。化合物 2 和 3 以及 2 的 N-2-四氢糠基（11）、N-烷基（12）和 N-氨基甲酰基（14）衍生物表现出动态的酮烯醇同分异构现象。这些吡啶的酰基衍生物具有易变性，被认为是活性酯。这些吡啶的单酰基酯衍生物与 5-FUra 类似物相结合，开发出了含有 5-FUra 降解抑制剂的新型抗肿瘤药物。其中，3-[3-(6-苯甲酰氧基-3-氰基-2-吡啶氧羰基)苯甲酰]-1-乙氧基甲基-5-氟尿嘧啶（BOF-A2）（22b）最为有效，目前正在进行第二阶段后期临床试验。

  DOI：

  10.1248/cpb.41.1498
• 作为产物：
  描述：

  氯甲基乙醚 以87%的产率得到
  参考文献：
  名称：

  KARPEJSKIJ M. YA.; MIXAJLOV S. M.; TSIEMINYA A. S.; ZIDERMAN A. A.; KRAVC+, XIMIYA GETEROTSIKL. SOEDIN., 1980, HO 11, 1541-1544

  摘要：

  DOI：

文献信息

• Studies on antitumor agents. V. Syntheses and antitumor activities of 5-fluorouracil derivatives.
  作者：JUNICHI YAMASHITA、ICHIRO YAMAWAKI、SHUICHI UEDA、MITSUGI YASUMOTO、NORIO UNEMI、SADAO HASHIMOTO

  DOI：10.1248/cpb.30.4258

  日期：——

  Six types of 5-fluorouracil (5-FU) derivatives were synthesized ; namely, 2, 4-di-O-substituted, 2-O-substituted, 4-O-substituted, 1, 3-disubstituted, 1-substituted and 3-substituted compounds. After oral administration of these compounds to rats, the blood levels of 5-FU were determined. Among O-substituted derivatives, a 4-O-substituted derivative was most easily activated to 5-FU and 2-O-substituted derivatives were next most easily activated. Among N-substituted derivatives, acyl and sulfonyl derivatives showed the highest 5-FU releasing abilities and 1-alkoxymethyl substituted derivatives showed low ability. N-Alkyl substituted derivatives were not activated to 5-FU. Several compounds which gave higher blood levels of 5-FU than that obtained with 1-(tetrahydro-2-furyl)-5-fluorouracil (Thf-FU), as well as same related compounds, were selected and their antitumor activities were examined. The 2-O-substituted derivatives, 2-butoxy-5-fluoro-4 (1H)-pyrimidone (11) and 2-benzyloxy-5-fluoro-4 (1H)-pyrimidone (19), were as effective as Thf-FU. The activities of 2, 4-di-O-substituted derivatives, 2, 4-dibutoxy-5-fluoropyrimidine (1) and 2, 4-dibenzyloxy-5-fluoropyrimidine (6), against Ehrlich carcinoma and against sarcoma 180, respectively, were the same as those of Thf-FU. The 1-substituted derivatives, 1-ethoxymethyl-5-fluorouracil (49) and 1-(1-ethoxy-1-phenylmethyl)-5-fluorouracil (50), were found to be as effective as Thf-FU.

  合成了六类氟尿嘧啶（5-FU）衍生物，即2,4-二-O-取代、2-O-取代、4-O-取代、1,3-二取代、1-取代和3-取代的化合物。在大鼠口服这些化合物后，测定了5-FU的血药浓度。在O-取代衍生物中，4-O-取代衍生物最容易被激活为5-FU，其次是2-O-取代衍生物。在N-取代衍生物中，酰基和磺酰基衍生物显示出最高的5-FU释放能力，1-烷氧甲基取代衍生物的释放能力较低。N-烷基取代衍生物未被激活为5-FU。选择了几种在血中5-FU水平高于1-(四氢-2-呋喃基)-5-氟尿嘧啶（Thf-FU）的化合物，以及一些相关化合物，并对其抗肿瘤活性进行了检测。2-O-取代衍生物，2-丁氧基-5-氟-4(1H)-嘧啶酮（11）和2-苄氧基-5-氟-4(1H)-嘧啶酮（19），与Thf-FU一样有效。2,4-二-O-取代衍生物，2,4-二丁氧基-5-氟嘧啶（1）和2,4-二苄氧基-5-氟嘧啶（6），对艾氏癌和肉瘤180的活性与Thf-FU相同。1-取代衍生物，1-乙氧甲基-5-氟尿嘧啶（49）和1-(1-乙氧基-1-苯甲基)-5-氟尿嘧啶（50），发现与Thf-FU一样有效。
• 5-Fluorouracil derivatives. X. Synthesis and antitumor activities of .ALPHA.-alkoxyalkyl-5-fluorouracils.
  作者：SHOICHIRO OZAKI、YUTAKA WATANABE、TOMONORI HOSHIKO、TOSHIO NAGASE、TOMIO OGASAWARA、HIROYUKI FURUKAWA、ATSUHIKO UEMURA、KATSUTOSHI ISHIKAWA、HARUKI MORI、AKIO HOSHI、MASAAKI IIGO、REIKO TOKUZEN

  DOI：10.1248/cpb.34.150

  日期：——

  With the aim of diminishing the toxicity of 5-fluorouracil (1) and obtaining biologically active derivatives of 1 suitable for oral administration, α-alkoxyalkyl groups were introduced at the 1-, 3-and 1, 3-positions of 1. Alkoxyalkylation can be effected by four methods : (i) reaction of 1-alkoxyalkyl chloride (2) with 1, (ii) reaction of acetal with 2, 4-bis (trimethylsiloxy)-5-fluoropy-rimidine, (iii) addition reaction of α-unsaturated ether with 1, (iv) aminolysis of 1-alkylthio-carbonyl-3-(1-alkoxyalkyl)-5-fluorouracil. The toxicity of the products was less than that of 1, and some of these compounds showed moderate antitumor activity against L-1210 leukemia.

  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，人们在 1-氟尿嘧啶的 1、3 和 1、3-位上引入了 α-烷氧基烷基。烷氧基烷基化可通过四种方法实现：(i) 1-烷氧基烷基氯（2）与 1 反应；(ii) 缩醛与 2，4-双（三甲基硅氧基）-5-氟嘧啶反应；(iii) α-不饱和醚与 1 的加成反应；(iv) 1-烷硫基-羰基-3-（1-烷氧基烷基）-5-氟尿嘧啶的氨解反应。这些产物的毒性小于 1，其中一些化合物对 L-1210 白血病具有中等程度的抗肿瘤活性。
• Enhancer of anti-tumour effect
  申请人：Yamasa Shoyu Kabushiki Kaisha

  公开号：EP0068268A1

  公开（公告）日：1983-01-05

  N6-acylated 3'-deoxyadenosines or phosphates thereof are disclosed as being effective for enhancing anti-tumor effect afforded by irradiation of or administration of an anti-tumor pharmaceutical to tumor-bearing animals.

  已公开的 N6-酰化 3'-脱氧腺苷或其磷酸酯可有效增强肿瘤动物通过照射或服用抗肿瘤药物所获得的抗肿瘤效果。
• Enhancer of antitumor effect
  申请人：Yamasa Shoyu Kabushiki Kaisha

  公开号：EP0079054A1

  公开（公告）日：1983-05-18

  An antitumor effect enhancer for antitumor agents comprising 9-β-D-arabinofuranosyl adenine, a chemotherapeutic comprising a combination of said enhancer with an antitumor agent and a use thereof are disclosed.

  本发明公开了一种由 9-β-D-arabinofuranosyl adenine 组成的抗肿瘤药抗肿瘤效果增强剂、一种由所述增强剂与抗肿瘤药组合而成的化疗药及其用途。
• A composition for increasing the anti-cancer activity of an anti-cancer compound
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：EP0180188A2

  公开（公告）日：1986-05-07

  A composition for increasing the anti-cancer activity of an anti-cancer compound selected from among 5-fluorouracil and a compound capable of producing 5-fluorouracil in vivo, the composition comprising an effective amount of a pyridine derivative represented by the formula wherein R1 is hydroxy or acyloxy, R2 and R4 are each hydrogen, halogen, amino, carboxyl, carbamoyl, cyano, nitro, lower alkyl, lower alkenyl or lower alkoxycarbonyl, R3 and R are each hydrogen, hydroxy or acyloxy; when at least one of R1, R3 and R5 is hydroxy, the structure of 1-position on the pyridine rina can be duetothe due to the keto-enol tautomerism, said hydrogen attached to nitrogen being optionally substituted with a substituent selected from the group consisting of lower alkyl, tetrahydrofuranyl, tetrahydropyranyl, lower alkoxy-lower alkyl, phthalidyl, carbamoyl, lower alkoxycarbonyl-lower alkylcarbamoyl, phenyl-lower alkoxy-lower alkyl, phenylcarbamoyl which may have a substituent on the phenyl ring, lower alkylcarbamoyl, carboxy-lower alkylcarbamoyl, lower alkylthio-lower alkyl and lower alkenyl, provided that the compound having the following formula is excluded, wherein a is hydrogen, lower alkyl, tetrahydrofuranyl, tetrahydropyranyl, lower alkoxy-lower alkyl, lower alkylcarbamoyl, lower alkylthio-lower alkyl or lower alkenyl.

  一种提高选自5-氟尿嘧啶和一种能在体内产生5-氟尿嘧啶的化合物的抗癌活性的组合物，该组合物包括有效量的由式表示的吡啶衍生物 其中 R1 是羟基或酰氧基，R2 和 R4 分别是氢、卤素、氨基、羧基、氨基甲酰基、氰基、硝基、低级烷基、低级烯基或低级烷氧基羰基，R3 和 R 分别是氢、羟基或酰氧基；当 R1、R3 和 R5 中至少有一个是羟基时，吡啶里纳上 1 位的结构可以是 当 R1、R3 和 R5 中至少有一个是羟基时，吡啶里纳上 1 位的结构可以是酮烯醇同分异构，所述连接到氮上的氢可选择被选自低烷基、四氢呋喃基、四氢吡喃基、低烷氧基低烷基、邻苯二甲酰基、氨基甲酰基、低烷氧基羰基低烷基氨基甲酰基组成的取代基取代、苯基-低级烷氧基-低级烷基、苯基氨基甲酰基（苯基环上可能有取代基）、低级烷基氨基甲酰基、羧基-低级烷基氨基甲酰基、低级烷硫基-低级烷基和低级烯基，但具有下式的化合物除外、 其中 a 为氢、低级烷基、四氢呋喃基、四氢呋喃基、低级烷氧基低级烷基、低级烷基氨基甲酰基、低级烷硫基低级烷基或低级烯基。