3-(2-morpholinoethyl)thiazolidine-2,4-dione | 1357306-20-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 3-(2-morpholinoethyl)thiazolidine-2,4-dione
• 英文别名: 3-(2-Morpholin-4-ylethyl)-1,3-thiazolidine-2,4-dione；3-(2-morpholin-4-ylethyl)-1,3-thiazolidine-2,4-dione
• CAS: 1357306-20-7
• 化学式: C₉H₁₄N₂O₃S
• mdl: MFCD25958416
• 分子量: 230.288
• InChiKey: SUAOWBXNBLQMQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.777
• 拓扑面积：
  75.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  苯丙醛 、 3-(2-morpholinoethyl)thiazolidine-2,4-dione 在 哌啶 作用下， 以 甲醇 为溶剂， 生成 3-(2-morpholinethyl)-5-(3-phenylpropylidene)thiazolidine-2,4-dione
  参考文献：
  名称：

  3,5-Disubstituted-thiazolidine-2,4-dione analogs as anticancer agents: Design, synthesis and biological characterization

  摘要：

  A series of 2,5-disubstituted-thiazolidine-2,4-dione analogs based on the newly identified lead 1, a potential anticancer agent via the inhibition of the Raf/MEK/extracellular signal regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascades, were synthesized and biologically characterized. A new lead structure, 15, was identified to have improved anti-proliferative activities in U937 cells, to induce apoptosis in U937, M12 and DU145 cancer cells, and to arrest U937 cells at the S-phase. Furthermore, Western blot analysis demonstrated a correlation of the anti-proliferative activity and blockade of the Raf/MEK/ERK and PI3K/Akt signaling pathways. Collectively, these results strongly encourage further optimization of 15 as a new lead with multi-target properties to develop more potent compounds as anticancer agents. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.10.031
• 作为产物：
  描述：

  3-(2-hydroxyethyl)thiazolidine-2,4-dione 在 4-二甲氨基吡啶 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 16.0h， 生成 3-(2-morpholinoethyl)thiazolidine-2,4-dione
  参考文献：
  名称：

  通过促进 β-连环蛋白和 Ras 降解治疗结直肠癌的新型 Ras 调节剂的结构优化

  摘要：

  Ras 蛋白一直被认为是抗癌治疗的一个迷人靶点，因为它的功能异常与癌症密切相关。然而，由于无法通过控制 Ras 激活机制来调节其故障，Ras 一直被认为是不可药用的。最近，针对 G12C 突变的 Lumakras 获得批准，Ras 在抗癌治疗中的治疗兴趣重新焕发活力。在这里，我们展示了一系列化合物，这些化合物通过利用 Wnt/β-catenin 通路与 Ras 之间关系的独特作用机制来抑制 Ras。KYA1797K (1)结合 axin 以稳定导致 Ras 磷酸化和随后降解的 β-catenin 破坏复合物，类似于典型的 β-catenin 调节。基于1的化学结构, 我们进行了结构优化并确定 3-(2-hydroxyethyl)-5-((6-(4-nitrophenyl)pyridin-2-yl)methylene)thiazolidine-2,4-dione ( 13d ) 为最有效的化合物

  DOI：

  10.1016/j.bioorg.2022.106234

文献信息

• Structural exploration, synthesis and pharmacological evaluation of novel 5-benzylidenethiazolidine-2,4-dione derivatives as iNOS inhibitors against inflammatory diseases
  作者：Liang Ma、Heying Pei、Lei Lei、Linhong He、Jinying Chen、Xiaolin Liang、Aihua Peng、Haoyu Ye、Mingli Xiang、Lijuan Chen

  DOI：10.1016/j.ejmech.2014.12.036

  日期：2015.3

  In our previous work, 3I inhibited the LPS-induced iNOS activity and NO production in RAW 264.7 cells and improved joint inflammation and cartilage destruction in inflammatory model. In this study, we synthesized 59 derivatives and bioisosteres on the basis of 3I by Knoevenagel condensation and biologically evaluated for the study of structure-activity relationship (SAR). We found that 7-44 suppressed the iNOS activity (IC50 25.2 mu M) and LPS-induced NO production (IC50 45.6 mu M) in RAW 264.7 cells. As for the SAR study, the dimethoxylphenyl group of 7-44 was potential for a further modification. At a dose of 10 mg/kg, oral administration of 7-44 possessed protective properties in both carrageenan-induced paw edema of male ICR mice and adjuvant-induced arthritis of Lewis female rats. Although the activity of 7-44 was slightly inferior, the PK profiles of 7-44 were superior to those of 3I. (C) 2014 Elsevier Masson SAS. All rights reserved.
• 3,5-Disubstituted-thiazolidine-2,4-dione analogs as anticancer agents: Design, synthesis and biological characterization
  作者：Kai Liu、Wei Rao、Hardik Parikh、Qianbin Li、Tai L. Guo、Steven Grant、Glen E. Kellogg、Shijun Zhang

  DOI：10.1016/j.ejmech.2011.10.031

  日期：2012.1

  A series of 2,5-disubstituted-thiazolidine-2,4-dione analogs based on the newly identified lead 1, a potential anticancer agent via the inhibition of the Raf/MEK/extracellular signal regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascades, were synthesized and biologically characterized. A new lead structure, 15, was identified to have improved anti-proliferative activities in U937 cells, to induce apoptosis in U937, M12 and DU145 cancer cells, and to arrest U937 cells at the S-phase. Furthermore, Western blot analysis demonstrated a correlation of the anti-proliferative activity and blockade of the Raf/MEK/ERK and PI3K/Akt signaling pathways. Collectively, these results strongly encourage further optimization of 15 as a new lead with multi-target properties to develop more potent compounds as anticancer agents. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Structural optimization of novel Ras modulator for treatment of Colorectal cancer by promoting β-catenin and Ras degradation
  作者：Seonghwi Choi、Hyuntae Kim、Won-Ji Ryu、Kang-Yell Choi、Taegun Kim、Doona Song、Gyoonhee Han

  DOI：10.1016/j.bioorg.2022.106234

  日期：2023.1

  optimization and identified 3-(2-hydroxyethyl)-5-((6-(4-nitrophenyl)pyridin-2-yl)methylene)thiazolidine-2,4-dione (13d) as the most potent compound. 13d displayed antitumor effects in a colorectal cancer model with enhanced inhibition activity on Ras. The results of this study suggest that the further development of 13d could contribute to the development of Ras inhibitors with novel mechanisms of action.

  Ras 蛋白一直被认为是抗癌治疗的一个迷人靶点，因为它的功能异常与癌症密切相关。然而，由于无法通过控制 Ras 激活机制来调节其故障，Ras 一直被认为是不可药用的。最近，针对 G12C 突变的 Lumakras 获得批准，Ras 在抗癌治疗中的治疗兴趣重新焕发活力。在这里，我们展示了一系列化合物，这些化合物通过利用 Wnt/β-catenin 通路与 Ras 之间关系的独特作用机制来抑制 Ras。KYA1797K (1)结合 axin 以稳定导致 Ras 磷酸化和随后降解的 β-catenin 破坏复合物，类似于典型的 β-catenin 调节。基于1的化学结构, 我们进行了结构优化并确定 3-(2-hydroxyethyl)-5-((6-(4-nitrophenyl)pyridin-2-yl)methylene)thiazolidine-2,4-dione ( 13d ) 为最有效的化合物