1-(1-ethoxy-1-phenylmethyl)-5-fluorouracil | 65315-16-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(1-ethoxy-1-phenylmethyl)-5-fluorouracil
• 英文别名: 1-[Ethoxy(phenyl)methyl]-5-fluoropyrimidine-2,4-dione
• CAS: 65315-16-4
• 化学式: C₁₃H₁₃FN₂O₃
• 分子量: 264.256
• InChiKey: SZMGBDOXHBMTOJ-UHFFFAOYSA-N

物化性质

• 熔点：
  128-129 °C(Solv: ethanol (64-17-5); water (7732-18-5))
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-氟脲嘧啶 、 ethyl-(α-chloro-benzyl)-ether 在 potassium carbonate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 5.0h， 以60%的产率得到1-(1-ethoxy-1-phenylmethyl)-5-fluorouracil
  参考文献：
  名称：

  5-Fluorouracil derivatives. X. Synthesis and antitumor activities of .ALPHA.-alkoxyalkyl-5-fluorouracils.

  摘要：

  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。

  DOI：

  10.1248/cpb.34.150

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。
• YAMASHITA, JUN-ICHI;YAMAWAKI, ICHIRO;UEDA, SHUICHI;YASUMOTO, MITSUGI;UNEM+, CHEM. AND PHARM. BULL., 1982, 30, N 12, 4258-4267
  作者：YAMASHITA, JUN-ICHI、YAMAWAKI, ICHIRO、UEDA, SHUICHI、YASUMOTO, MITSUGI、UNEM+

  DOI：——

  日期：——