N-(4-acetylphenyl)thiophene-2-sulfonamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(4-acetylphenyl)thiophene-2-sulfonamide
• 化学式: C₁₂H₁₁NO₃S₂
• mdl: MFCD01141523
• 分子量: 281.356
• InChiKey: RARIONWIINHXFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.083
• 拓扑面积：
  99.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(4-acetylphenyl)thiophene-2-sulfonamide 在 phenyltrimethylammonium tribromide 、 三乙胺 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 16.58h， 生成 N-(4-(4-hydroxy-3-(pyridin-3-ylmethyl)-2-thioxothiazolidin-4-yl)phenyl) thiophene-2-sulfonamide
  参考文献：
  名称：

  Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2-thione derivatives as tumor cell specific pyruvate kinase M2 activators

  摘要：

  Pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic glycolysis of cancer cells. Activation of PKM2 may alter aberrant metabolism in cancer cells. In this study, we discovered a 4-hydroxy-thiazolidine-2-thione compound 2 as a novel PKM2 activator from a random screening of an in-house compound library. Then a series of novel 4-hydroxy-thiazolidine-2-thione derivatives were designed and synthesized for screening as potent PKM2 activators. Among these, some compounds showed higher PKM2 activation activity than lead compound 2 and also exhibited significant anti proliferative activities on human cancer cell lines at nanomolar concentration. The compound 5w was identified as the most potent antitumor agent, which showed excellent anti-proliferative effects with IC50 values from 0.46 mu M to 0.81 mu M against H1299, HCT116, Hela and PC3 cell lines. 5w also showed less cytotoxicity in non-tumor cell line HELF compared with cancer cells. In addition, Preliminary pharmacological studies revealed that 5w arrests the cell cycle at the G2/M phase in HCT116 cell line. The best PKM2 activation by compound 5t was rationalized through docking studies. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.11.023
• 作为产物：
  描述：

  2-噻吩磺酰氯 、 4-氨基苯乙酮 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以1.2 g的产率得到N-(4-acetylphenyl)thiophene-2-sulfonamide
  参考文献：
  名称：

  新型变构蛋白二硫化物异构酶抑制剂的设计、合成和生物学评价。

  摘要：

  蛋白质二硫键异构酶 (PDI) 负责内质网 (ER) 中的新生蛋白质折叠，对胶质母细胞瘤的存活至关重要。为了提高 PDI 抑制剂 BAP2 (( E)-3-(3-(4-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzonitron) 的效力，我们设计并合成了 67 种类似物。我们确定 PDI 抑制依赖于查耳酮支架的 A 环羟基，并且磺酰胺链中 cLogP 的增加提高了效力。对接研究表明，BAP2 和类似物与 PDI 的 b' 结构域中的 His256 结合，而 His256 突变为 Ala 会消除 BAP2 类似物的活性。BAP2 和优化的类似物 59 具有适度的硫醇反应性；然而，我们建议 BAP2 类似物对 PDI 的抑制取决于 b' 结构域。重要的是，类似物抑制胶质母细胞瘤细胞生长，诱导 ER 应激，增加 G2M 检查点蛋白的表达，降低 DNA 修复蛋白的表达。总的来说，我们的结果支持抑制

  DOI：

  10.1021/acs.jmedchem.8b01951

文献信息

• Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2-thione derivatives as tumor cell specific pyruvate kinase M2 activators
  作者：Ridong Li、Xianling Ning、Shuo Zhou、Zhiqiang Lin、Xingyu Wu、Hong Chen、Xinyu Bai、Xin Wang、Zemei Ge、Runtao Li、Yuxin Yin

  DOI：10.1016/j.ejmech.2017.11.023

  日期：2018.1

  Pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic glycolysis of cancer cells. Activation of PKM2 may alter aberrant metabolism in cancer cells. In this study, we discovered a 4-hydroxy-thiazolidine-2-thione compound 2 as a novel PKM2 activator from a random screening of an in-house compound library. Then a series of novel 4-hydroxy-thiazolidine-2-thione derivatives were designed and synthesized for screening as potent PKM2 activators. Among these, some compounds showed higher PKM2 activation activity than lead compound 2 and also exhibited significant anti proliferative activities on human cancer cell lines at nanomolar concentration. The compound 5w was identified as the most potent antitumor agent, which showed excellent anti-proliferative effects with IC50 values from 0.46 mu M to 0.81 mu M against H1299, HCT116, Hela and PC3 cell lines. 5w also showed less cytotoxicity in non-tumor cell line HELF compared with cancer cells. In addition, Preliminary pharmacological studies revealed that 5w arrests the cell cycle at the G2/M phase in HCT116 cell line. The best PKM2 activation by compound 5t was rationalized through docking studies. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Design, Synthesis, and Biological Evaluation of Novel Allosteric Protein Disulfide Isomerase Inhibitors
  作者：Suhui Yang、Andrea Shergalis、Dan Lu、Anahita Kyani、Ziwei Liu、Mats Ljungman、Nouri Neamati

  DOI：10.1021/acs.jmedchem.8b01951

  日期：2019.4.11

  survival. To improve the potency of lead PDI inhibitor BAP2 (( E)-3-(3-(4-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzonitrile), we designed and synthesized 67 analogues. We determined that PDI inhibition relied on the A ring hydroxyl group of the chalcone scaffold and cLogP increase in the sulfonamide chain improved potency. Docking studies revealed that BAP2 and analogues bind to His256 in the b' domain of

  蛋白质二硫键异构酶 (PDI) 负责内质网 (ER) 中的新生蛋白质折叠，对胶质母细胞瘤的存活至关重要。为了提高 PDI 抑制剂 BAP2 (( E)-3-(3-(4-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzonitron) 的效力，我们设计并合成了 67 种类似物。我们确定 PDI 抑制依赖于查耳酮支架的 A 环羟基，并且磺酰胺链中 cLogP 的增加提高了效力。对接研究表明，BAP2 和类似物与 PDI 的 b' 结构域中的 His256 结合，而 His256 突变为 Ala 会消除 BAP2 类似物的活性。BAP2 和优化的类似物 59 具有适度的硫醇反应性；然而，我们建议 BAP2 类似物对 PDI 的抑制取决于 b' 结构域。重要的是，类似物抑制胶质母细胞瘤细胞生长，诱导 ER 应激，增加 G2M 检查点蛋白的表达，降低 DNA 修复蛋白的表达。总的来说，我们的结果支持抑制