(RS)-1-<<3-(2-hydroxyethoxy)-1-methoxy>propyl>-5-fluorouracil

• 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: (RS)-1-<<3-(2-hydroxyethoxy)-1-methoxy>propyl>-5-fluorouracil
• 英文别名: 5-Fluoro-1-[3-(2-hydroxyethoxy)-1-methoxypropyl]pyrimidine-2,4-dione
• 化学式: C₁₀H₁₅FN₂O₅
• 分子量: 262.238
• InChiKey: HMKDGFNXUVNBIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (RS)-1-<<3-(2-hydroxyethoxy)-1-methoxy>propyl>-5-fluorouracil 在 四氯化碳 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以89%的产率得到(RS)-1-[3-(2-chloroethoxy)-1-methoxypropyl]-5-fluorouracil
  参考文献：
  名称：

  Chemical modifications on the acyclic moiety of 3-(2-hydroxyethoxy)-1-alkoxypropyl nucleobases. 2. Differentiation and growth inhibition in rhabdomyosarcoma cells after exposure to a novel 5-fluorouracil acyclonucleoside

  摘要：

  A series of new 5FU acyclonucleoside analogues has been synthesized and tested for their in vitro cytotoxicity versus HT-29 colon carcinoma. The only active compound is 1-{[3-(3-cloro-2-hydroxypropoxy)-1-methoxy]propoxy}-5-fluorouracil 14, which is 8-fold less active than 5-fluorouracil. The rest of the newly prepared compounds showed no significant activity We selected 14 as the drug in the treatment of an human embryonal cell line RD derived from rhabdomyosarcoma. Such treatment caused time-dependent growth inhibition. Interestingly, RD cells treated with 14 at a concentration of 90 mu M for 6 days showed phenotypic differentiation, with increased expression of desmin, alpha-actinin and tropomyosin. We conclude that exposure of this human embryonal rhabdomyosarcoma cell line to a 90 mu M concentration released the neoplastic cells from their blockade, allowing them to recover normal myogenic development. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(97)00415-8
• 作为产物：
  描述：

  5-氟脲嘧啶 、 5-Methoxy-1,4-dioxepane 在 三甲基氯硅烷 、 四氯化锡 、 六甲基二硅氮烷 作用下， 以 乙腈 为溶剂， 反应 0.75h， 以31%的产率得到(RS)-1-<<3-(2-hydroxyethoxy)-1-methoxy>propyl>-5-fluorouracil
  参考文献：
  名称：

  5-氟尿嘧啶衍生物。1.无环核苷通过氯化锡（IV）介导的烷氧基-1,4-二杂庚烷的区域特异性开环

  摘要：

  5-氟尿嘧啶在室温下在氯化锡（IV），三甲基氯硅烷和六甲基二硅氮烷的存在下与七元缩醛1a-g反应，得到1-{[[3-（2-（羟乙基杂）-1-烷氧基]烷基] -5-氟尿嘧啶2A-F和1 - {[2-（3-羟基丙氧基）-1-异丙氧基]乙基} -5-氟尿嘧啶2克在31-86％的产率。杂原子在环缩醛的1位上的存在和氯化锡（IV）能够进行1,4-螯合，似乎在1a-g的区域特异性开环中施加了它们的影响。对2b和（1 R，3 R）-2e和（1 R，3S）-2e清楚地表明，N 1（sp 2）-C 1 -C 2 -C 3部分倾向于以薄纱构象折叠。评估化合物2b-g对HEp人类细胞的抗肿瘤活性，显示2c的活性是5-FU的4倍。与5-FU的毒性作用相比，所研究的药物未显示任何明显的毒性。

  DOI：

  10.1016/0040-4020(96)00439-5

文献信息

• 5-fluorouracil derivatives. 1. Acyclonucleosides through a tin (IV) chloride-mediated regiospecific ring opening of alkoxy-1,4-diheteroepanes
  作者：J. Campos、M.J. Pineda、J.A. Gómez、A. Entrena、M.A. Trujillo、M.A. Gallo、A. Espinosa

  DOI：10.1016/0040-4020(96)00439-5

  日期：1996.6

  and the use of tin (IV) chloride, capable of a 1,4-chelation, seem to impose their influence in the regiospecific ring opening of 1a-g. The conformational analyses carried out on 2b and (1R,3R)-2e and (1R,3S)-2e clearly indicate that the N1(sp2)-C1-C2-C3 moiety tends to fold in a gauche conformation. The antitumour activities of compounds 2b-g were assessed against HEp human cells showing that 2c is 4-fold

  5-氟尿嘧啶在室温下在氯化锡（IV），三甲基氯硅烷和六甲基二硅氮烷的存在下与七元缩醛1a-g反应，得到1-[[3-（2-（羟乙基杂）-1-烷氧基]烷基] -5-氟尿嘧啶2A-F和1 - [2-（3-羟基丙氧基）-1-异丙氧基]乙基} -5-氟尿嘧啶2克在31-86％的产率。杂原子在环缩醛的1位上的存在和氯化锡（IV）能够进行1,4-螯合，似乎在1a-g的区域特异性开环中施加了它们的影响。对2b和（1 R，3 R）-2e和（1 R，3S）-2e清楚地表明，N 1（sp 2）-C 1 -C 2 -C 3部分倾向于以薄纱构象折叠。评估化合物2b-g对HEp人类细胞的抗肿瘤活性，显示2c的活性是5-FU的4倍。与5-FU的毒性作用相比，所研究的药物未显示任何明显的毒性。
• Synthesis of novel 5-fluorouracil derivatives with 1,4-oxaheteroepane moieties
  作者：Jose A. Gómez、María A. Trujillo、Joaquín Campos、Miguel A. Gallo、Antonio Espinosa

  DOI：10.1016/s0040-4020(98)00815-1

  日期：1998.10

  A series of new ring-expanded isosteres (1,4-oxaheteroepanes) of Ftorafur [1-(2-tetrahydrofuranyl)-5-fluorouracil] has been synthesized. The branching of C-3 of the seven-membered cycloacetal and the electronegativity of the Y group on the 3-YCH2 moities (Y being H, I and Cl), respectively, seem to direct their regiochemical and stereochemical outcome. The more electronegative the group Y is (and favouring accordingly the formation of an external ion pair), the more diastereoselectivity that is reached. The in vitro cytotoxicity versus HT-29 has been tested, showing that cis-3g was the only moderately active compound. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Chemical modifications on the acyclic moiety of 3-(2-hydroxyethoxy)-1-alkoxypropyl nucleobases. 2. Differentiation and growth inhibition in rhabdomyosarcoma cells after exposure to a novel 5-fluorouracil acyclonucleoside
  作者：Jose A. Gómez、Joaquín Campos、Juan A. Marchal、María A. Trujillo、Consolación Melguizo、José Prados、Miguel A. Gallo、Antonia Aránega、Antonio Espinosa

  DOI：10.1016/s0040-4020(97)00415-8

  日期：1997.5

  A series of new 5FU acyclonucleoside analogues has been synthesized and tested for their in vitro cytotoxicity versus HT-29 colon carcinoma. The only active compound is 1-[3-(3-cloro-2-hydroxypropoxy)-1-methoxy]propoxy}-5-fluorouracil 14, which is 8-fold less active than 5-fluorouracil. The rest of the newly prepared compounds showed no significant activity We selected 14 as the drug in the treatment of an human embryonal cell line RD derived from rhabdomyosarcoma. Such treatment caused time-dependent growth inhibition. Interestingly, RD cells treated with 14 at a concentration of 90 mu M for 6 days showed phenotypic differentiation, with increased expression of desmin, alpha-actinin and tropomyosin. We conclude that exposure of this human embryonal rhabdomyosarcoma cell line to a 90 mu M concentration released the neoplastic cells from their blockade, allowing them to recover normal myogenic development. (C) 1997 Elsevier Science Ltd.