N'-((5-methoxy-1H-indol-3-yl)methylene)-4-methylbenzenesulfonohydrazide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N'-((5-methoxy-1H-indol-3-yl)methylene)-4-methylbenzenesulfonohydrazide
• 英文别名: N-[(5-methoxy-1H-indol-3-yl)methylideneamino]-4-methylbenzenesulfonamide
• 化学式: C₁₇H₁₇N₃O₃S
• 分子量: 343.406
• InChiKey: VVGBJIHPXOUOIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  91.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N'-((5-methoxy-1H-indol-3-yl)methylene)-4-methylbenzenesulfonohydrazide 、 N1-(2,4-二氟苯基)-2-氯乙胺 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以14.62%的产率得到N-(2,4-difluorophenyl)-2-(5-methoxy-3-((2-tosylhydrazono)methyl)-1H-indol-1-yl)acetamide
  参考文献：
  名称：

  Design and bio-evaluation of indole derivatives as potent Kv1.5 inhibitors

  摘要：

  Atrial fibrillation (AF) is one of the common arrhythmias that threaten human health. Kv1.5 potassium channel is reported as an efficacious and safe target for the treatment of AF. In this paper, we designed and synthesized three series of compounds through modifying the lead compound RH01617 that was screened out by the pharmacophore model we reported earlier. All of the compounds were evaluated by the whole-patch lamp technology and most of them possessed potent inhibitory activities against Kv1.5. Compounds IIIi and IIIl were evaluated for the target selectivity as well as the pharmacodynamic effects in an isolated rat model. Due to the promising pharmacological behavior, compound IIIl deserves further pharmacodynamic and pharmacokinetic evaluations. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.041
• 作为产物：
  描述：

  对甲苯磺酰氯 在 对甲苯磺酸 、 一水合肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 0.5h， 生成 N'-((5-methoxy-1H-indol-3-yl)methylene)-4-methylbenzenesulfonohydrazide
  参考文献：
  名称：

  小分子介导的癌细胞内质网应激诱导

  摘要：

  内质网（ER）是重要的亚细胞细胞器之一，控制着蛋白质生物合成、折叠、错误折叠和解折叠等多种功能。因此，内质网中这些通路的失调与癌症的发生和进展有关。随后，靶向癌细胞中的 ER 成为下一代抗癌治疗中一种有趣的非正统策略。然而，开发选择性靶向 ER 进行癌症治疗的小分子仍然难以捉摸且尚未探索。为了解决这个问题，我们通过简短的化学合成策略开发了一种新型的磺酰肼-腙小分子库。我们鉴定出一种荧光小分子，定位于 HeLa 细胞的内质网 (ER)，诱导 ER 应激，随后触发自噬，随后被氯喹（自噬抑制剂）抑制以引发细胞凋亡。这种小分子与氯喹单药或联合治疗对不同癌细胞表现出显着的杀伤功效，从而为内质网生物学开发新型抗癌疗法开辟了新方向。

  DOI：

  10.1039/d1md00095k

文献信息

• CuI-catalyzed highly regioselective C H functionalization of indoles using indole-3-tosylhydrazones as carbene precursor: An efficient synthesis of 3,3-bis(indolyl)methane derivatives
  作者：Priya Kamboj、Sunil Dutt、Sourav Chakroborty、Vikas Tyagi

  DOI：10.1016/j.tetlet.2019.151162

  日期：2019.10

  Herein, we have developed a novel approach for synthesizing symmetrical and unsymmetrical 3,3-bis(indolyl)methane derivatives via CuI-catalyzed CH functionalization of indole using indole-3-tosylhydrazones as carbene precursor. This procedure works well with different substitutions such as NO2, Br, CH3 and OMe on indole or indole-3-tosylhydrazones and features high regioselectivity for C-3 functionalization

  本文中，我们开发了一种新颖的方法，该方法通过使用吲哚-3-甲苯磺酰azo作为卡宾前体通过CuI催化的吲哚的C H官能化合成对称和不对称的3,3-双（吲哚基）甲烷衍生物。该方法与吲哚或吲哚-3-甲苯磺酰hydr上的NO 2，Br，CH 3和OMe的不同取代效果很好，并且对C-1和N-1位置的C-3功能化具有很高的区域选择性。此外，我们还从吲哚-3-羧醛开始以一锅法揭示了该方案的可行性。
• Silver(<scp>i</scp>)-catalyzed annulation for the regioselective synthesis of N-imino-γ-carbolinium ylides from hydrazones of indole-3-carbonyl derivatives and propargylic alcohols
  作者：Yu Zhu、Xin-Rui Shen、Hai-Tao Tang、Min Lin、Zhuang-Ping Zhan

  DOI：10.1039/c4ob02020k

  日期：——

  N-imino-γ-carbolinium ylides via AgOTf-catalyzed iminoannulation has been developed. This transformation proceeds via a silver(I) triflate-catalyzed consecutive Friedel–Crafts reaction/N–C bond formation sequence between the readily available indole derivatives and propargylic alcohols.

  已经开发了一种通过AgOTf催化的亚氨基环化反应合成N-亚氨基-γ-咔啉鎓基团的区域选择性有效合成方法。这种转变通过三氟甲磺酸银（I）催化的连续Friedel-Crafts反应/ N-C键在易于获得的吲哚衍生物和炔丙醇之间形成的顺序进行。
• Small molecule-mediated induction of endoplasmic reticulum stress in cancer cells
  作者：Shalini Pandey、Virender Kumar Sharma、Ankur Biswas、Mayurika Lahiri、Sudipta Basu

  DOI：10.1039/d1md00095k

  日期：——

  development of small molecules to selectively target the ER for cancer therapy remained elusive and unexplored. To address this, herein, we have developed a novel small molecule library of sulfonylhydrazide-hydrazones through a short and concise chemical synthetic strategy. We identified a fluorescent small molecule that localized into the endoplasmic reticulum (ER) of HeLa cells, induced ER stress

  内质网（ER）是重要的亚细胞细胞器之一，控制着蛋白质生物合成、折叠、错误折叠和解折叠等多种功能。因此，内质网中这些通路的失调与癌症的发生和进展有关。随后，靶向癌细胞中的 ER 成为下一代抗癌治疗中一种有趣的非正统策略。然而，开发选择性靶向 ER 进行癌症治疗的小分子仍然难以捉摸且尚未探索。为了解决这个问题，我们通过简短的化学合成策略开发了一种新型的磺酰肼-腙小分子库。我们鉴定出一种荧光小分子，定位于 HeLa 细胞的内质网 (ER)，诱导 ER 应激，随后触发自噬，随后被氯喹（自噬抑制剂）抑制以引发细胞凋亡。这种小分子与氯喹单药或联合治疗对不同癌细胞表现出显着的杀伤功效，从而为内质网生物学开发新型抗癌疗法开辟了新方向。
• Design and bio-evaluation of indole derivatives as potent Kv1.5 inhibitors
  作者：Xiaoke Guo、Qian Yang、Jing Xu、Li Zhang、Hongxi Chu、Peng Yu、Yingying Zhu、Jinglian Wei、Weilin Chen、Yaozhong Zhang、Xiaojin Zhang、Haopeng Sun、Yiqun Tang、Qidong You

  DOI：10.1016/j.bmc.2013.08.041

  日期：2013.11

  Atrial fibrillation (AF) is one of the common arrhythmias that threaten human health. Kv1.5 potassium channel is reported as an efficacious and safe target for the treatment of AF. In this paper, we designed and synthesized three series of compounds through modifying the lead compound RH01617 that was screened out by the pharmacophore model we reported earlier. All of the compounds were evaluated by the whole-patch lamp technology and most of them possessed potent inhibitory activities against Kv1.5. Compounds IIIi and IIIl were evaluated for the target selectivity as well as the pharmacodynamic effects in an isolated rat model. Due to the promising pharmacological behavior, compound IIIl deserves further pharmacodynamic and pharmacokinetic evaluations. (C) 2013 Elsevier Ltd. All rights reserved.