ethyl 3-(2'-chloroacetamido)-4,9-dioxo-2,3,4,9-tetrahydronaphtho[2,3-b]thiophen-3-carboxylate | 1027000-67-4

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: ethyl 3-(2'-chloroacetamido)-4,9-dioxo-2,3,4,9-tetrahydronaphtho[2,3-b]thiophen-3-carboxylate
• 英文别名: 3-(2'-chloro)-acetamide-3-ethoxycarbonyl-2,3-dihydrothieno[2,3-b]naphtho-4,9-dione；3-(2'-chloro)acetamide-3-ethoxycarbonyl-2,3-dihydrothieno[2,3-b]naphtho-4,9-dione
• CAS: 1027000-67-4
• 化学式: C₁₇H₁₄ClNO₅S
• 分子量: 379.821
• InChiKey: LMYYWFBKPXOQGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.72
• 重原子数：
  25.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  89.54
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ethyl 3-(2'-chloroacetamido)-4,9-dioxo-2,3,4,9-tetrahydronaphtho[2,3-b]thiophen-3-carboxylate 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以78%的产率得到2'-chloro-N-(3-(hydroxymethyl)-4,9-dioxo-2,3,4,9-tetrahydronaphtho[2,3-b] thiophen-3-yl)-acetamide
  参考文献：
  名称：

  Dihydrithieno[2,3-b]naphto-4,9-dione analogues as anticancer agents: Synthesis and in cell pharmacological studies

  摘要：

  The synthesis of a series of highly functionalized DNTQ-based derivatives is described. In vitro, most of the compounds exerted a cytotoxic effect against several tumour cell lines comparable to or greater than that of doxorubicin. Here we demonstrate that compound 14, the less cardiotoxic compound of this series, induced cell differentiation and was distributed mainly in the cytoplasm in the human glioblastoma LN229 cell line. Moreover, compound 14 reduced both cellular glucose uptake and serine/threonine kinase ART expression, and triggered cell apoptosis. These findings suggest that highly functionalized DTNQ-based derivatives are promising pharmacological tools for the study of human solid tumours. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.07.044
• 作为产物：
  描述：

  DTNQ 、 氯乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 ethyl 3-(2'-chloroacetamido)-4,9-dioxo-2,3,4,9-tetrahydronaphtho[2,3-b]thiophen-3-carboxylate
  参考文献：
  名称：

  Dihydrithieno[2,3-b]naphto-4,9-dione analogues as anticancer agents: Synthesis and in cell pharmacological studies

  摘要：

  The synthesis of a series of highly functionalized DNTQ-based derivatives is described. In vitro, most of the compounds exerted a cytotoxic effect against several tumour cell lines comparable to or greater than that of doxorubicin. Here we demonstrate that compound 14, the less cardiotoxic compound of this series, induced cell differentiation and was distributed mainly in the cytoplasm in the human glioblastoma LN229 cell line. Moreover, compound 14 reduced both cellular glucose uptake and serine/threonine kinase ART expression, and triggered cell apoptosis. These findings suggest that highly functionalized DTNQ-based derivatives are promising pharmacological tools for the study of human solid tumours. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.07.044

文献信息

• Design, Synthesis, and Cytotoxic Evaluation of Acyl Derivatives of 3-Aminonaphtho[2,3-<i>b</i>]thiophene-4,9-dione, a Quinone-Based System
  作者：Isabel Gomez-Monterrey、Pietro Campiglia、Claudio Aquino、Alessia Bertamino、Ilaria Granata、Alfonso Carotenuto、Diego Brancaccio、Paola Stiuso、Ilaria Scognamiglio、M. Rosaria Rusciano、Angela Serena Maione、Maddalena Illario、Paolo Grieco、Bruno Maresca、Ettore Novellino

  DOI：10.1021/jm200094h

  日期：2011.6.23

  A series of 3-acyl derivatives of the dihydronaphtho[2,3-b]thiophen-4,9-dione system were studied with respect to cytotoxicity and topoisomerase II inhibitory activity. These analogues were designed as electron-deficient anthraquinone analogues with potential intercalation ability. Derivatives 3-(diethylamino)-N-(4,9-dioxo-4,9-dihydronaphtho[2,3-b]thiophen-3-yl)propanamide (11m) and 3-(2-(dimethyl-amino)ethylamino)-N-(4,9-dioxo-4,9-dihydronaphtho[2,3-b]thiophen-3-yl)propanamide (11p) showed a high efficacy in cell lines that were highly resistant to treatment with doxorubicin, such as MDA-MB435 (melanoma), IGROV (ovarian), and SF-295 (glioblastoma) human cell lines. Both compounds inhibit topoisomerase II mediated relaxation of DNA, while only 11p incites arrest at the S phase in Caco-2 cells, inducing a delay of cell cycle progression and an increase of cell differentiation. The ability of these derivatives to modulate small heat shock proteins and cardiotoxicy effects was also explored. In addition, the DNA-binding properties of these compounds were investigated and discussed.
• Spiro[(dihydropyrazin-2,5-dione)-6,3′-(2′,3′-dihydrothieno[2,3-<i>b</i>]naphtho-4′,9′-dione)]-Based Cytotoxic Agents: Structure–Activity Relationship Studies on the Substituent at N4-Position of the Diketopiperazine Domain
  作者：Isabel Gomez-Monterrey、Pietro Campiglia、Alfonso Carotenuto、Paola Stiuso、Alessia Bertamino、Marina Sala、Claudio Aquino、Paolo Grieco、Silvana Morello、Aldo Pinto、Pio Ianelli、Ettore Novellino

  DOI：10.1021/jm7013056

  日期：2008.5.1

  Analogues of the previously reported potent cytotoxic spiro[(dihydropyrazine-2,5-dione)-6,3'-(2',3'-dihydrothieno[2,3-b]naphtho-4',9'-dione)] derivatives (3, 3') were prepared to explore new structural requirements at the diketopiperazine domain for the cytotoxic activity. The in vitro activity was evaluated against the MCF-7 human breast carcinoma and SW 620 human colon carcinoma cell lines. The 4-[(2-N,N-dimethyl)amino]ethyl (6i), and the 4-(2-pyrrolydin)ethyl (61) derivatives emerged as the most potent compounds of this series, with a cytotoxic activity comparable to that of doxorubicin. These compounds, in both racemic and pure enantiomeric forms, showed also a high efficacy in cell lines resistant to doxorubicin (MCF-7/Dx) and in cell lines that were highly resistant to treatment with doxorubicin, such as HEK-293 (kidney), M-14 (melanoma), and HeLa (cervical adenocarcinoma) human cell lines. In addition, the effects on growth and cell cycle progression in CaCo-2 cell fine (colon adenocarcinoma) and DNA-binding properties were investigated.