1,2-bis[4-(2-thenoyloxymethyl)-3,5-dioxopiperazin-1-yl]ethane | 98632-22-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1,2-bis[4-(2-thenoyloxymethyl)-3,5-dioxopiperazin-1-yl]ethane
• 英文别名: [4-[2-[3,5-dioxo-4-(thiophene-2-carbonyloxymethyl)piperazin-1-yl]ethyl]-2,6-dioxopiperazin-1-yl]methyl thiophene-2-carboxylate
• CAS: 98632-22-5
• 化学式: C₂₂H₂₂N₄O₈S₂
• 分子量: 534.571
• InChiKey: CDFXNUKQVLYKAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  190
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  1,2-二(3,5-二氧代哌嗪-1-基)乙烷 在 吡啶 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 1,2-bis[4-(2-thenoyloxymethyl)-3,5-dioxopiperazin-1-yl]ethane
  参考文献：
  名称：

  Synthesis and antitumor properties of N1-acyloxymethyl derivatives of bis(2,6-dioxopiperazines).

  摘要：

  许多双(2,6-二氧哌嗪)I、ICRF-154的N1-酰氧甲基衍生物VI被制备并测试了其抗肿瘤活性。将I与甲醛反应得到结晶的双(N1-羟甲基)衍生物VII，该衍生物在不同条件下酰化得到双(N1-酰氧甲基)衍生物VI。研究了VI对小鼠P388白血病的抗肿瘤活性。发现几种双(N1-酰氧甲基)化合物如苯乙酰氧甲基VI-6、甲氧羰基氧甲基VI-41、异丁氧羰基氧甲基VI-44和呋喃甲酰甲基VI-38具有强大的抗肿瘤活性。另一方面，酰基中含有氨基或羧酸功能的水溶性酯类显示出较低的活性。这些双(N-1-酰氧甲基)衍生物VI可能通过体内非特异性酯酶水解为母体双(2,6-二氧哌嗪)I来展现其抗肿瘤活性。

  DOI：

  10.1248/cpb.37.2976

文献信息

• Bis-dioxopiperazine derivatives, process for their preparation,
  申请人：Zenyaku Kogyo Kabushiki Kaisha

  公开号：US04650799A1

  公开（公告）日：1987-03-17

  Disclosed are novel bis-dioxopiperazine derivatives and non-toxic salts thereof, process for their preparation, antitumor agents comprising them and compositions containing them. The bis-dioxopiperazine derivatives are represented by the following general formula (I): ##STR1## wherein R represents an alkyl radical having 1 to 17 carbon atoms, a cycloalkyl radical having 3 to 7 carbon atoms, a lower alkyl radical having a substituent or substituents selected from the group consisting of halogeno, carboxy, alkoxycarbonyl having 2 to 5 carbon atoms, lower alkoxy, substituted or unsubstituted phenoxy, naphthyloxy, substituted or unsubstituted phenylthio, substituted or unsubstituted phenyl and naphthyl, a substituted or unsubstituted phenyl lower alkenyl radical, a substituted or unsubstituted phenyl radical, a naphthyl radical, a heterocyclic radical selected from the group consisting of pyridyl, furyl and thienyl, an alkoxy radical having 1 to 8 carbon atoms, a substituted or unsubstituted phenyl lower alkoxy radical, or a substituted or unsubstituted phenoxy radical. A substituent or substituents on R may be selected from the group consisting of lower alkyl, halogeno, lower alkoxy, acyloxy having 2 to 5 carbon atoms, methylenedioxy, carboxy, amino, methanesulfonylamino and nitro. The above-mentioned "lower alkyl", "lower alkoxy" and "lower alkenyl" respectively refer to alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms and alkenyl having 2 to 4 carbon atoms.

  揭示了新颖的双二氧哌嗪衍生物及其无毒盐，其制备方法，包含它们的抗肿瘤剂和含有它们的组合物。双二氧哌嗪衍生物由以下一般式（I）表示：##STR1##其中R代表具有1至17个碳原子的烷基基团，具有3至7个碳原子的环烷基基团，具有来自卤素、羧基、具有2至5个碳原子的烷氧羰基、辅基或辅基的下位烷氧基、取代或未取代的苯氧基、萘氧基、取代或未取代的苯硫基、取代或未取代的苯基和萘基、取代或未取代的苯下位烯基基团、取代或未取代的苯基基团、萘基团、选自吡啶基、呋喃基和噻吩基的杂环基团、具有1至8个碳原子的烷氧基、取代或未取代的苯下位烷氧基团，或取代或未取代的苯氧基团。R上的辅基或辅基可选自下位烷基、卤素、下位烷氧基、具有2至5个碳原子的酰氧基、亚甲二氧基、羧基、氨基、甲磺酰氨基和硝基的群。上述“下位烷基”、“下位烷氧基”和“下位烯基”分别指具有1至4个碳原子的烷基，具有1至4个碳原子的烷氧基和具有2至4个碳原子的烯基。
• Bis-dioxopiperazine derivatives, process for their preparation, antitumor agents comprising them and compositions containing them
  申请人：ZENYAKU KOGYO KABUSHIKI KAISHA

  公开号：EP0140327B1

  公开（公告）日：1990-05-23
• ——
  作者：SAJ SYUNTE、 TAKASEH MUNEHAKI

  DOI：——

  日期：——
• US4650799A
  申请人：——

  公开号：US4650799A

  公开（公告）日：1987-03-17
• Synthesis and antitumor properties of N1-acyloxymethyl derivatives of bis(2,6-dioxopiperazines).
  作者：Jun Chao CAI、Han Li SHU、Cai Fang TANG、Toshihiko KOMATSU、Toshiyuki MATSUNO、Toshiharu NARITA、Shin-ichi YAGUCHI、Yuji KOIDE、Muneaki TAKASE

  DOI：10.1248/cpb.37.2976

  日期：——

  Many N1-acyloxymethyl derivatives VI of bis(2, 6-dioxopiperazine) I, ICRF-154, were prepared and tested for antitumor activity. The treatment of I with formaldehyde gave a crystalline bis(N1-hydroxymethyl) derivative VII, which was acylated under various conditions to give bis(N1-acyloxymethyl) derivatives VI. Antitumor activity of VI against P388 leukemia in mice was studied.Several bis(N1-acyloxymethyl)compounds such as phenylacetyloxymethyl VI-6, methoxycarbonyloxymethyl VI-41, isobutoxycarbonyloxymethyl VI-44, and furancarboxymethyl VI-38 compounds were found to have potent antitumor activities. On the other hand, water-soluble esters having an amine or a carboxylic acid function in their acyl groups showed rather reduced activity.These bis(N-1-acyloxymethyl) derivatives VI were presumably hydrolyzed into the parent bis(2, 6-dioxopiperazine) I by nonspecific esterase in the body to exhibit their antitumor activity.

  许多双(2,6-二氧哌嗪)I、ICRF-154的N1-酰氧甲基衍生物VI被制备并测试了其抗肿瘤活性。将I与甲醛反应得到结晶的双(N1-羟甲基)衍生物VII，该衍生物在不同条件下酰化得到双(N1-酰氧甲基)衍生物VI。研究了VI对小鼠P388白血病的抗肿瘤活性。发现几种双(N1-酰氧甲基)化合物如苯乙酰氧甲基VI-6、甲氧羰基氧甲基VI-41、异丁氧羰基氧甲基VI-44和呋喃甲酰甲基VI-38具有强大的抗肿瘤活性。另一方面，酰基中含有氨基或羧酸功能的水溶性酯类显示出较低的活性。这些双(N-1-酰氧甲基)衍生物VI可能通过体内非特异性酯酶水解为母体双(2,6-二氧哌嗪)I来展现其抗肿瘤活性。