N-(3-aminopropyl)-2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetamide | 84568-63-8

• 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: N-(3-aminopropyl)-2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetamide
• CAS: 84568-63-8
• 化学式: C₉H₁₃FN₄O₃
• 分子量: 244.226
• InChiKey: BXCVKNFIGRUTRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4'-demethyl-4-deoxypodophyllotoxin 4'-(p-nitrophenyl) carbonate 、 N-(3-aminopropyl)-2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetamide 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以70%的产率得到4-deoxyl-4'-O-deoxypodophyllotoxin-4'-yl(3-(2-(5-fluorouracil-1-yl)acetamido)propyl)carbamate
  参考文献：
  名称：

  Synthesis of hybrid 4-deoxypodophyllotoxin–5-fluorouracil compounds that inhibit cellular migration and induce cell cycle arrest

  摘要：

  A series of deoxypodophyllotoxin-5-fluorouracil hybrid compounds were synthesized, and their cytotoxic activity was evaluated using four human cancer cell lines (HeLa, A549, HCT-8, and HepG2) and the human normal cell line WI-38. The synthesized compounds exhibited greater cytotoxic activity in tumor cells and reduced toxicity in the normal cell line compared with the anticancer drug VP-16 and 5-FU. Additionally, the most potent of these compounds-40-O-demethyl-4-deoxypodophyllotoxin-40-yl 4-((6-(2-(5-fluorouracil-yl) acetamido) hexyl) amino)-4-oxobutanoate (compound 22)-induced cell-cycle arrest in the G2/M phase by regulating levels of cdc2, cyclinB1, and p-cdc2 in A549 cells. Furthermore, compound 22 may inhibited the migration of A549 cells via down-regulation of MMP-9 and up-regulation of TIMP-1. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.02.013
• 作为产物：
  描述：

  2,4-二氧代-5-氟-3,4-二氢-1(2H)-嘧啶乙酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(3-aminopropyl)-2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetamide
  参考文献：
  名称：

  Synthesis of hybrid 4-deoxypodophyllotoxin–5-fluorouracil compounds that inhibit cellular migration and induce cell cycle arrest

  摘要：

  A series of deoxypodophyllotoxin-5-fluorouracil hybrid compounds were synthesized, and their cytotoxic activity was evaluated using four human cancer cell lines (HeLa, A549, HCT-8, and HepG2) and the human normal cell line WI-38. The synthesized compounds exhibited greater cytotoxic activity in tumor cells and reduced toxicity in the normal cell line compared with the anticancer drug VP-16 and 5-FU. Additionally, the most potent of these compounds-40-O-demethyl-4-deoxypodophyllotoxin-40-yl 4-((6-(2-(5-fluorouracil-yl) acetamido) hexyl) amino)-4-oxobutanoate (compound 22)-induced cell-cycle arrest in the G2/M phase by regulating levels of cdc2, cyclinB1, and p-cdc2 in A549 cells. Furthermore, compound 22 may inhibited the migration of A549 cells via down-regulation of MMP-9 and up-regulation of TIMP-1. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.02.013

文献信息

• Synthesis and biological activity of N-substituted 5-fluorouracil-1-acetamides
  作者：Helmut Pischel、Antonín Holý、Jiří Veselý、Günther Wagner、Dieter Cech

  DOI：10.1135/cccc19822806

  日期：——

  Reaction of 5-fluorouracil (I) with sodium chloroacetate in the presence of sodium hydride afforded a mixture of 5-fluorouracil-1-acetic acid (II) and 5-fluorouracil-3-acetic acid (III). p-Nitrophenyl 5-fluorouracil-1-acetate (IV) reacted with amines in methanol or dimethylformamide to give N-substituted 5-fluorouracil-1-acetamides V. The following amides were prepared: diethylamide Vc, n-hexylamide Vd, cyclohexylamide Ve, adamantylamide Vf, anilide Vg, benzylamide Vh, benzhydrylamide Vi, pyrrolidide Vj, piperidide Vk, morpholide Vl, 3-dimethylaminopropylamide Vm, 3-aminopropylamide Vn, 2-hydroxyethylamide Vo, bis(2-hydroxyethyl)amide Vp and tris(hydroxymethyl)methylamide Vq. Compounds Vc-Vq do not inhibit the growth of Escherichia coli in concentrations up to 1 mg/ml. Compounds Vf and Vh have a weak, compound Vq a significant, inhibition effect on the growth of L-1210 mouse leukemic cells in vitro in concentrations 1.5 . 10^-5 mol l^-1.

  5-氟尿嘧啶（I）在氢氧化钠存在下与氯乙酸钠反应，生成5-氟尿嘧啶-1-乙酸（II）和5-氟尿嘧啶-3-乙酸（III）的混合物。对硝基苯基5-氟尿嘧啶-1-乙酸酯（IV）在甲醇或二甲基甲酰胺中与胺反应，生成N-取代的5-氟尿嘧啶-1-乙酰胺（V）。制备了以下酰胺：双乙酰胺（Vc）、正己基酰胺（Vd）、环己基酰胺（Ve）、金刚烷基酰胺（Vf）、苯甲酰胺（Vg）、苄基酰胺（Vh）、苯甲基酰胺（Vi）、吡咯烷酰胺（Vj）、哌啶酰胺（Vk）、吗啉酰胺（Vl）、3-二甲氨基丙酰胺（Vm）、3-氨基丙酰胺（Vn）、2-羟乙酰胺（Vo）、双（2-羟乙基）酰胺（Vp）和三（羟甲基）甲基酰胺（Vq）。化合物Vc-Vq在浓度高达1毫克/毫升时不抑制大肠杆菌的生长。化合物Vf和Vh对L-1210小鼠白血病细胞的生长有微弱的抑制作用，化合物Vq在浓度为1.5×10^-5摩尔/升时对体外细胞生长有显著的抑制作用。
• PISCHEL, H.;HOLY, A.;VESELY, J.;WAGNER, G.;CECH, D., COLLECT. CZECH. CHEM. COMMUN., 1982, 47, N 10, 2806-2813
  作者：PISCHEL, H.、HOLY, A.、VESELY, J.、WAGNER, G.、CECH, D.

  DOI：——

  日期：——