N-(4-acetylphenyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamide | 941152-68-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(4-acetylphenyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamide
• 英文别名: N-(4-acetylphenyl)-2,3-dihydro-1,4-benzodioxine-6-sulfonamide
• CAS: 941152-68-7
• 化学式: C₁₆H₁₅NO₅S
• 分子量: 333.365
• InChiKey: UAFPASLELYGQIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  90.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(4-acetylphenyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-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-4-ylmethyl)-2-thioxothiazolidin-4-yl)phenyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-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：

  2,3-二氢-1,4-苯并二氧-6-磺酰氯 、 4-氨基苯乙酮 在 吡啶 作用下， 以80%的产率得到N-(4-acetylphenyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamide
  参考文献：
  名称：

  Pyrazolines for the Modulation of PKM2

  摘要：

  该发明涉及取代吡唑啉化合物和激活PKM2的方法。这些化合物和方法在治疗或预防癌症、细胞增殖紊乱、炎症性疾病、代谢紊乱和免疫系统紊乱等疾病或疾病中具有用途。

  公开号：

  US20120302609A1

文献信息

• Pyrazolines for the Modulation of PKM2
  申请人：Becker Oren M.

  公开号：US20120302609A1

  公开（公告）日：2012-11-29

  The invention relates to pyrazoline substituted compounds and methods for activating PKM2. The compounds and methods are useful in treating or preventing a disease or disorder selected from cancer, cell proliferative disorder, inflammatory disorder, metabolic disorder, and immune system disorder.

  该发明涉及取代吡唑啉化合物和激活PKM2的方法。这些化合物和方法在治疗或预防癌症、细胞增殖紊乱、炎症性疾病、代谢紊乱和免疫系统紊乱等疾病或疾病中具有用途。
• Single-Electron-Transfer-Generated Aryl Sulfonyl Ammonium Salt: Metal-Free Photoredox-Catalyzed Modular Construction of Sulfonamides
  作者：Fengying Yan、Qing Li、Shanshan Fu、Yuxing Yang、Duoqi Yang、Shun Yao、Man Song、Hong Deng、Xianwei Sui

  DOI：10.1021/acscatal.4c00816

  日期：2024.4.5

  construction of aryl sulfonamides via an aryl sulfonyl ammonium salt intermediate, which was generated in situ via a SET event, has been established. A variety of structurally diverse primary, secondary, and tertiary aryl sulfonamides were synthesized rapidly from abundant amines or sodium azide under mild conditions. Notably, the primary aliphatic amine, which remains challenging in the Cu-catalyzed protocols

  磺胺类化合物在有机合成和药物化学中具有突出的作用。然而，用于芳基磺酰胺模块化结构的通用合成平台仍然难以捉摸。在此，通过芳基磺酰铵盐中间体建立了无金属光氧化还原催化的芳基磺酰胺三组分结构，该中间体通过SET 事件原位生成。在温和条件下，由丰富的胺或叠氮化钠快速合成了多种结构多样的伯、仲和叔芳基磺酰胺。值得注意的是，脂肪族伯胺在铜催化方案中仍然具有挑战性，但在这种方法中效果良好。此外，以氟化氢钾为亲核试剂，也可以顺利合成芳基磺酰氟。这种转换的潜在效用在三种生物活性药物化合物的简便构建中得到了证明。初步的机理研究表明，芳基磺酰基自由基和芳基磺酰铵盐是这种机械创新方法中的关键中间体。
• α-Mercaptoketone based histone deacetylase inhibitors
  作者：Paul L. Wash、Timothy Z. Hoffman、Brandon M. Wiley、Céline Bonnefous、Nicholas D. Smith、Michael S. Sertic、Charles M. Lawrence、Kent T. Symons、Phan-Manh Nguyen、Kevin D. Lustig、Xin Guo、Tami Annable、Stewart A. Noble、Jeffrey H. Hager、Christian A. Hassig、James W. Malecha

  DOI：10.1016/j.bmcl.2008.10.058

  日期：2008.12

  In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel alpha-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, alpha-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo. (C) 2008 Elsevier Ltd. All rights reserved.
• [EN] 3, 5 -DIPHENYL- SUBSTITUTED PYRAZOLINES FOR THE TREATMENT OF CANCER, PROLIFERATIVE, INFLAMMATORY OR AUTOIMMUNE DISEASES<br/>[FR] PYRAZOLINES 3,5-DIPHÉNYL SUBSTITUÉES POUR LE TRAITEMENT DU CANCER, DE MALADIES PROLIFÉRATIVES, INFLAMMATOIRES OU AUTO-IMMUNES
  申请人：DYNAMIX PHARMACEUTICALS LTD

  公开号：WO2012160447A1

  公开（公告）日：2012-11-29

  The invention relates to pyrazoline substituted compounds and methods for activating PKM2. The compounds and methods are useful in treating or preventing a disease or disorder selected from cancer, cell proliferative disorder, inflammatory disorder, metabolic disorder, and immune system disorder.
• 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.