trans-tetrahydrodipirazino<1,2-a:2',1'-c>pyrazine-1,3,10,12(2H,4H,9H,11H)-tetrone | 79751-02-3

• 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: trans-tetrahydrodipirazino<1,2-a:2',1'-c>pyrazine-1,3,10,12(2H,4H,9H,11H)-tetrone
• 英文别名: trans-tetrahydrodipirazino[1,2-a:2',1'-c]pyrazine-1,3,10,12(2H,4H,9H,11H)-tetrone；(1R,2R)-4,7,10,13-tetrazatricyclo[8.4.0.02,7]tetradecane-3,5,12,14-tetrone
• CAS: 79751-02-3
• 化学式: C₁₀H₁₂N₄O₄
• 分子量: 252.23
• InChiKey: CLECXPZAFASKTB-HTQZYQBOSA-N

物化性质

• 沸点：
  617.5±55.0 °C(Predicted)
• 密度：
  1.61±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  98.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  吗啉 、 聚合甲醛 、 trans-tetrahydrodipirazino<1,2-a:2',1'-c>pyrazine-1,3,10,12(2H,4H,9H,11H)-tetrone 以 水 、 二甲基亚砜 为溶剂， 反应 5.0h， 以71.7%的产率得到2,11-bis(morpholinomethyl)-trans-tetrahydrodipyrazino<1,2-a:2',1'-c>pyrazine-1,3,10,12(2H,4H,9H,11H)tetrone
  参考文献：
  名称：

  Stereoselective antitumor properties in the Lewis Lung carcinoma model using bis(morpholinomethyl) derivatives of tricyclic bis(dioxopiperazines)

  摘要：

  Geometric isomers of 2,11-bis(morpholinomethyl)tetrahydrodipyrazino[1,2-a:2',1'-c]pyraz ine-1, 3,10,12-(2H,4H,9H,11H)-tetrone (3 and 4) and the parent bisimides (1 and 2) were studied for their stereoselective antimetastatic activity in the Lewis Lung carcinoma model. The morpholinomethyl cis-syn-trans isomer 4 was more effective as an inhibitor of metastasis than the other three analogues. Using a postamputation protocol, the order of decreasing activity was cis morpholinomethyl analogue 4 greater than trans morpholinomethyl analogue 3 greater than parent cis imide 2 greater than parent trans imide 1. Increased activity observed for the morpholinomethyl derivatives may reflect differences in solubility and delivery (prodrug) or an intrinsic antitumor activity of the morpholinomethyl-N functionality.

  DOI：

  10.1021/jm00146a025
• 作为产物：
  描述：

  diethyl cis-2,3-dicarbamoyl-1,4-piperazinediacetate 在 sodium 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以71%的产率得到trans-tetrahydrodipirazino<1,2-a:2',1'-c>pyrazine-1,3,10,12(2H,4H,9H,11H)-tetrone
  参考文献：
  名称：

  Synthesis and antimetastatic properties of stereoisomeric tricyclic bis(dioxopiperazine) analogs in a B16 melanoma model

  摘要：

  The synthesis for trans and cis tricyclic bis(dioxopiperazine)s 5 and 6 from pyrazine-2,3-dicarboxamide (7) is described. Stereoselective antimetastatic activity differences for these analogues were observed following pretreatment of B16-F10 melanoma cells in vitro. Activities for these isomers were compared with selected intermediates, and the data are discussed in relation to previous results obtained with cis- and trans-cyclopropane analogues.

  DOI：

  10.1021/jm00143a013

文献信息

• WITIAK, D. T.;TRIVEDI, B. K.;CAMPOLITO, L. B.;ZWILLING, B. S.;REICHES, N.+, J. MED. CHEM., 1981, 24, N 11, 1329-1332
  作者：WITIAK, D. T.、TRIVEDI, B. K.、CAMPOLITO, L. B.、ZWILLING, B. S.、REICHES, N.+

  DOI：——

  日期：——
• WITIAK, D. T.;TRIVEDI, BHARAT, K.;SCHMID, F. A., J. MED. CHEM., 1985, 28, N 8, 1111-1113
  作者：WITIAK, D. T.、TRIVEDI, BHARAT, K.、SCHMID, F. A.

  DOI：——

  日期：——
• Stereoselective antitumor properties in the Lewis Lung carcinoma model using bis(morpholinomethyl) derivatives of tricyclic bis(dioxopiperazines)
  作者：Donald T. Witiak、Bharat K. Trivedi、Franz A. Schmid

  DOI：10.1021/jm00146a025

  日期：1985.8

  Geometric isomers of 2,11-bis(morpholinomethyl)tetrahydrodipyrazino[1,2-a:2',1'-c]pyraz ine-1, 3,10,12-(2H,4H,9H,11H)-tetrone (3 and 4) and the parent bisimides (1 and 2) were studied for their stereoselective antimetastatic activity in the Lewis Lung carcinoma model. The morpholinomethyl cis-syn-trans isomer 4 was more effective as an inhibitor of metastasis than the other three analogues. Using a postamputation protocol, the order of decreasing activity was cis morpholinomethyl analogue 4 greater than trans morpholinomethyl analogue 3 greater than parent cis imide 2 greater than parent trans imide 1. Increased activity observed for the morpholinomethyl derivatives may reflect differences in solubility and delivery (prodrug) or an intrinsic antitumor activity of the morpholinomethyl-N functionality.
• Synthesis and antimetastatic properties of stereoisomeric tricyclic bis(dioxopiperazine) analogs in a B16 melanoma model
  作者：Donald T. Witiak、Bharat K. Trivedi、Laura B. Campolito、Bruce S. Zwilling、Nancy A. Reiches

  DOI：10.1021/jm00143a013

  日期：1981.11

  The synthesis for trans and cis tricyclic bis(dioxopiperazine)s 5 and 6 from pyrazine-2,3-dicarboxamide (7) is described. Stereoselective antimetastatic activity differences for these analogues were observed following pretreatment of B16-F10 melanoma cells in vitro. Activities for these isomers were compared with selected intermediates, and the data are discussed in relation to previous results obtained with cis- and trans-cyclopropane analogues.