ethyl 3-amino-4,9-dioxo-2,3,4,9-tetrahydrothieno[2,3-g]quinoline-3-carboxylate | 668467-71-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl 3-amino-4,9-dioxo-2,3,4,9-tetrahydrothieno[2,3-g]quinoline-3-carboxylate
• 英文别名: 3-amino-3-ethoxycarbonyldihydrothieno[2,3-g]quinolin-4,9-dione；ethyl 3-amino-4,9-dioxo-2H-thieno[2,3-g]quinoline-3-carboxylate
• CAS: 668467-71-8
• 化学式: C₁₄H₁₂N₂O₄S
• 分子量: 304.326
• InChiKey: FGBQTZJYNSERFX-UHFFFAOYSA-N

物化性质

• 熔点：
  >200 °C (decomp)
• 沸点：
  504.6±50.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-叔丁氧羰基-L-丙氨酸 、 ethyl 3-amino-4,9-dioxo-2,3,4,9-tetrahydrothieno[2,3-g]quinoline-3-carboxylate 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 3-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-4,9-dioxo-2H-thieno[2,3-g]quinoline-3-carboxylate
  参考文献：
  名称：

  Unprecedented synthesis of a novel amino quinone ring system via oxidative decarboxylation of quinone-based α,α-amino esters

  摘要：

  描述了一种从相应的α,α-氨基酸酯合成新型醌基胺及其衍生物的非同寻常且高效的合成方法。该过程涉及在碱性水解过程中通过氢转移实现醌基体系的氧化脱羧。这种合成方法以良好的产率，快速地合成出可能具有细胞毒性的新型醌类化合物。

  DOI：

  10.1039/b918898c
• 作为产物：
  描述：

  ethyl 4,9-dioxo-3-(3-phenyl-2-(3-phenylthioureido)propanamido)-2,3,4,9-tetrahydrothieno[2,3-g]quinoline-3-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 ethyl 3-amino-4,9-dioxo-2,3,4,9-tetrahydrothieno[2,3-g]quinoline-3-carboxylate
  参考文献：
  名称：

  Antitumor Agents 6. Synthesis, Structure−Activity Relationships, and Biological Evaluation of Spiro[imidazolidine-4,3′-thieno[2,3-g]quinoline]-tetraones and Spiro[thieno[2,3-g]quinoline-3,5′-[1,2,4]triazinane]-tetraones with Potent Antiproliferative Activity

  摘要：

  Two series of quinolinquinone derivatives, 2'H-spiro[imidazolidine-4,3'-thieno[2,3-g]quinoline]-2,4',5,9'-tetraones (2a-n) and 2H-spiro[thieno[2,3-g]quinoline-3.5'-[1,2,4]triazinane]-3',4,6',9-tetraones (3a-e), were designed and synthesized using the previously described ethyl 3-amino-4,9-dioxo-2,3,4,9-tetrahydrothieno[2,3-g]quinoline-3-carboxylate (1) as a starting material. All compounds were evaluated for their anti proliferative activity against a panel of representative liquid and solid human tumor cell lines and exhibit IC(50) values in the micromolar/submicromolar range. Series 2 displayed higher cytotoxicity than did series 3. The nature of the substituents on both imidazoline and triazinane N1 nitrogen markedly affected the activity profile of these series. Spectrophotometric and fluorescence measurements as well as Unwinding assays performed on the most cytotoxic compounds, 2c, 2g, and 2k, showed that they are nonintercalative DNA agents and inhibit the catalytic activity of Topo II in a concentration-dependent mode. 2g was the most active Topo II inhibitor with activity levels comparable to those of VP-16.

  DOI：

  10.1021/jm8007689

文献信息

• A practical, green, and selective approach toward the synthesis of pharmacologically important quinone-containing heterocyclic systems using alumina-catalyzed Michael addition reaction
  作者：Sabrina Castellano、Alessia Bertamino、Isabel Gomez-Monterrey、Marisabella Santoriello、Paolo Grieco、Pietro Campiglia、Gianluca Sbardella、Ettore Novellino

  DOI：10.1016/j.tetlet.2007.11.148

  日期：2008.1

  A convenient method for double Michael additions to quinone systems catalyzed by Al2O3, is reported. The advantages of this method include the use of a cheap and environment-friendly catalyst, a straightforward isolation of the pure product by filtration, high yields, and excellent selectivity, thus providing rapid access to useful building blocks for the preparation of biologically active quinones

  报道了一种方便的方法，用于通过Al 2 O 3催化将迈克尔双加成到醌体系中。该方法的优点包括使用便宜且环境友好的催化剂，通过过滤直接分离纯产物，高收率和优异的选择性，从而为制备生物活性醌提供了快速获得有用的结构单元的途径。
• Antitumor Agents. 3. Design, Synthesis, and Biological Evaluation of New Pyridoisoquinolindione and Dihydrothienoquinolindione Derivatives with Potent Cytotoxic Activity
  作者：Adele Bolognese、Gaetano Correale、Michele Manfra、Antonio Lavecchia、Orazio Mazzoni、Ettore Novellino、Paolo La Colla、Giuseppina Sanna、Roberta Loddo

  DOI：10.1021/jm030918b

  日期：2004.2.1

  1-aryl-3-ethoxycarbonyl-pyrido[2,3-g]isoquinolin-5,10-diones (PIQDs, 1-7), were designed on the basis of a molecular model obtained by aligning the common quinolinquinone substructure of 5H-pyrido[3,2-a]phenoxazin-5-one (PPH) and some known anticancer agents. A Diels-Alder reaction between quinolin-5,8-dione (QD) and a 2-azadiene, formed by demolition of 2-aryl-1,3-thiazolidine ethyl esters (T compounds)

  根据通过比对共同点而获得的分子模型，设计了新的抗增殖化合物，即1-芳基-3-乙氧基羰基-吡啶并[2,3-g]异喹啉-5,10-二酮（PIQD，1-7）。 5H-吡啶并[3,2-a]苯恶嗪-5-one（PPH）的喹啉醌亚结构和一些已知的抗癌药。喹啉5,8-二酮（QD）与2-氮杂二烯之间的Diels-Alder反应是由2-芳基-1,3-噻唑烷乙酯（T化合物）分解形成的，用于制备1-7和异构体1-芳基-3-乙氧基羰基吡啶并[3，2-g]异喹啉-5，10-二酮（8-14）。其他两种化合物，3-氨基-3-乙氧基羰基二氢噻吩并[2,3-g]喹啉-4,9-二酮（15）和3-氨基-3-乙氧基羰基二氢噻吩并[3,2-g]喹啉-4.9 -二酮（16），是由QD的1，4迈克尔反应与通过打开T化合物形成的硫醇盐类反应而产生的，从反应混合物中回收。评估了1-16的抗增殖活性，针对代表性的人类液体和固体肿瘤细胞系。这些化合物的IC（50）的中值范围为2
• Reaction between quinone and thiazolidine. A study on the formation mechanism of new antiproliferative quinolindiones
  作者：Adele Bolognese、Gaetano Correale、Michele Manfra、Antonio Lavecchia、Ettore Novellino、Vincenzo Barone

  DOI：10.1016/j.tet.2004.06.098

  日期：2004.9

  Reaction between quinolinquinone and thiazolidine in basic medium was investigated. 2-Arylthiazolidine-4-carboxylic acid ethyl esters undergo two different cleavages in basic medium, yielding the 1-aryl-2-azadiene and a thiolic species. In the presence of quinolinquinone, the isomeric 1-aryl-3-ethoxycarbonyl-pyridoisoquinolin-5,10-diones and 3-amino-3-ethoxycarbonyl-dihydrothienoquinolin-4,9-diones are formed by a hetero-Diels-Alder reaction and 1,4-Michael addition reaction, respectively. A mechanism for the formation of the reaction products is presented. (C) 2004 Elsevier Ltd. All rights reserved.
• Unprecedented synthesis of a novel amino quinone ring system via oxidative decarboxylation of quinone-based α,α-amino esters
  作者：Pietro Campiglia、Claudio Aquino、Alessia Bertamino、Nicoletta De Simone、Marina Sala、Sabrina Castellano、Marisabella Santoriello、Paolo Grieco、Ettore Novellino、Isabel M. Gomez-Monterrey

  DOI：10.1039/b918898c

  日期：——

  An unusual and efficient method for the synthesis of new quinone-based amine and its derivatives from the corresponding α,α-amino ester is described. The procedure involves the quinone-based system's oxidative decarboxylation via hydride transfer throughout basic hydrolysis. This synthetic method provides, with good yields, rapid access to new potentially cytotoxic quinones.

  描述了一种从相应的α,α-氨基酸酯合成新型醌基胺及其衍生物的非同寻常且高效的合成方法。该过程涉及在碱性水解过程中通过氢转移实现醌基体系的氧化脱羧。这种合成方法以良好的产率，快速地合成出可能具有细胞毒性的新型醌类化合物。
• Antitumor Agents 6. Synthesis, Structure−Activity Relationships, and Biological Evaluation of Spiro[imidazolidine-4,3′-thieno[2,3-<i>g</i>]quinoline]-tetraones and Spiro[thieno[2,3-<i>g</i>]quinoline-3,5′-[1,2,4]triazinane]-tetraones with Potent Antiproliferative Activity
  作者：Adele Bolognese、Gaetano Correale、Michele Manfra、Anna Esposito、Ettore Novellino、Antonio Lavecchia

  DOI：10.1021/jm8007689

  日期：2008.12.25

  Two series of quinolinquinone derivatives, 2'H-spiro[imidazolidine-4,3'-thieno[2,3-g]quinoline]-2,4',5,9'-tetraones (2a-n) and 2H-spiro[thieno[2,3-g]quinoline-3.5'-[1,2,4]triazinane]-3',4,6',9-tetraones (3a-e), were designed and synthesized using the previously described ethyl 3-amino-4,9-dioxo-2,3,4,9-tetrahydrothieno[2,3-g]quinoline-3-carboxylate (1) as a starting material. All compounds were evaluated for their anti proliferative activity against a panel of representative liquid and solid human tumor cell lines and exhibit IC(50) values in the micromolar/submicromolar range. Series 2 displayed higher cytotoxicity than did series 3. The nature of the substituents on both imidazoline and triazinane N1 nitrogen markedly affected the activity profile of these series. Spectrophotometric and fluorescence measurements as well as Unwinding assays performed on the most cytotoxic compounds, 2c, 2g, and 2k, showed that they are nonintercalative DNA agents and inhibit the catalytic activity of Topo II in a concentration-dependent mode. 2g was the most active Topo II inhibitor with activity levels comparable to those of VP-16.