1-(phenylsulfonyl)-1H-indole-4-carbonitrile

• 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: 1-(phenylsulfonyl)-1H-indole-4-carbonitrile
• 英文别名: 1-(benzenesulfonyl)indole-4-carbonitrile
• 化学式: C₁₅H₁₀N₂O₂S
• 分子量: 282.323
• InChiKey: FDEQMHVWVAAXPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  71.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(phenylsulfonyl)-1H-indole-4-carbonitrile 在 tris-(dibenzylideneacetone)dipalladium(0) 、 乙醛肟 、 palladium diacetate 、 caesium carbonate 、 三苯基膦 、 sodium hydroxide 、 lithium diisopropyl amide 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 39.0h， 生成 1-(4-(苄基氨基)-7,8-二氢-5H-吡喃并[4,3-D]嘧啶-2-基)-2-甲基-1H-吲哚-4-甲酰胺
  参考文献：
  名称：

  Discovery of a new class of valosine containing protein (VCP/P97) inhibitors for the treatment of non-small cell lung cancer

  摘要：

  Valosine containing protein (VCP/p97) is a member of the AAA ATPase family involved in several essential cellular functions and plays an important role in the ubiquitin-mediated degradation of misfolded proteins. P97 has a significant role in maintaining the cellular protein homeostasis for tumor cell growth and survival and has been found overexpressed in many tumor types. No new molecule entities based on p97 target were approved in clinic. Herein, a series of novel pyrimidine structures as p97 inhibitors were designed and synthesized. After enzymatic evaluations, structure-activity relationships (SAR) were discussed in detailed. Among the screened compounds, derivative 35 showed excellent enzymatic inhibitory activity (IC50, 36 nM). The cellular inhibition results showed that compound 35 had good antiproliferative activity against the non-small cell lung cancer A549 cells (IC50, 1.61 mu M). Liver microsome stability showed that the half-life of compound 35 in human liver microsome was 42.3 min, which was more stable than the control CB-5083 (25.8 min). The in vivo pharmacokinetic results showed that the elimination phase half-lives of compound 35 were 4.57 h for ig and 3.64 h for iv, respectively and the oral bioavailability was only 4.5%. These results indicated that compound 35 could be effective for intravenous treatment of non-small cell lung cancer.

  DOI：

  10.1016/j.bmc.2018.12.036
• 作为产物：
  描述：

  7-(4-chlorophenylthio)-6,7-dihydro-1-(phenylsulfonyl)-1H-indol-4(5H)-one 在 吡啶 、 zinc(II) iodide 、 三氯氧磷 作用下， 生成 1-(phenylsulfonyl)-1H-indole-4-carbonitrile
  参考文献：
  名称：

  一种新的，通用的4-取代吲哚类化合物。（S）-（-）-吲哚洛尔和（±）-创新霉素的合成

  摘要：

  通过使用7-芳硫基-6-7-二氢吲哚-4（5 H）和5作为共同的中间体，已经开发了一种合成4-取代的吲哚的新方法。该方法适用于（S）-（-）-哌多洛尔（11）和（±）-创新霉素（16）的合成。

  DOI：

  10.1016/0040-4039(93)85109-a

文献信息

• A new, general entry to 4-substituted indoles. Synthesis of (S)-(−)-pindolol and (±)-chuangxinmycin
  作者：Hiroyuki Ishibashi、Takashi Tabata、Kyoko Hanaoka、Hiroko Iriyama、Susumu Akamatsu、Masazumi Ikeda

  DOI：10.1016/0040-4039(93)85109-a

  日期：1993.1

  A new method for synthesis of 4-substituted indoles has been developed by using the 7-arylthio-6-7-dihydroindol-4(5H) one5 as a common intermediate. The method was applied to the synthesis of (S)-(−)-pindolol (11) and (±)-chuangxinmycin (16).

  通过使用7-芳硫基-6-7-二氢吲哚-4（5 H）和5作为共同的中间体，已经开发了一种合成4-取代的吲哚的新方法。该方法适用于（S）-（-）-哌多洛尔（11）和（±）-创新霉素（16）的合成。
• Development of Red‐Shifted and Fluorogenic Nucleoside and Oligonucleotide Diarylethene Photoswitches
  作者：Theresa Kolmar、Antonia Becker、Ronja A. Pfretzschner、Alina Lelke、Andres Jäschke

  DOI：10.1002/chem.202103133

  日期：2021.12.9

  The core structure of nucleoside based diarylethenes was modified, with the aim of bathochromically shifting the absorption wavelength in the visible range (λmax,vis) and to introduce photomodulatable fluorescence. Extending the π-system of the bridging unit resulted in a desired red shift of λmax,vis and fluorogenicity could be obtained by the introduction of a fluorescent adenosine analogue.

  对基于核苷的二芳基乙烯的核心结构进行了修改，目的是使吸收波长在可见光范围 (λ max,vis ) 发生红移，并引入可光调制的荧光。扩展桥接单元的 π 系统导致所需的 λ max,vis的红移，并且可以通过引入荧光腺苷类似物来获得荧光性。
• [EN] MONOCYCLIC PYRIMIDINE/PYRIDINE COMPOUNDS AS INHIBITORS OF P97 COMPLEX<br/>[FR] COMPOSÉS MONOCYCLIQUES PYRIMIDINE/PYRIDINE COMME INHIBITEURS DU COMPLEXE P97
  申请人：WUSTROW DAVID

  公开号：WO2015089218A1

  公开（公告）日：2015-06-18

  Monocyclic pyrimidine and pyridine compounds having a benzyl amine substituent at the 4 position and a 5:6 bicyclic heteroaryl substituent at the 2 position of the pyrimidine or pyridine ring as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the ring are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.

  在4位上具有苄胺取代基的单环嘧啶和吡啶化合物，以及在2位上具有5:6双环杂芳基取代基的嘧啶或吡啶环，还可以在环的其他位置取代烷基、官能基和/或芳香基成分。这些化合物是含有p97的AAA蛋白酶复合物的抑制剂，并且是用于治疗与p97生物活性相关的疾病如癌症的有效药物。
• General asymmetric synthesis of 2,2,2-trifluoro-1-(1H-indol-3- and -2-yl)ethanamines
  作者：Lingmin Wu、Chen Xie、Jie Zhou、Haibo Mei、Vadim A. Soloshonok、Jianlin Han、Yi Pan

  DOI：10.1016/j.jfluchem.2015.01.001

  日期：2015.2

  functionalization of the pyrrole ring of an indole structure with (2,2,2-trifluoro)ethylamine moiety allowing for general access to two novel classes of trifluoromethyl-containing indoles. We found that under the Friedel–Crafts reaction conditions (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimine (1) easily reacts with indole derivatives affording the target 3-substituted products, while LDA-promoted reactions

  这项工作描述了吲哚结构的吡咯环具有（2,2,2-三氟）乙胺部分的不对称官能化，该官能团使得能够普遍获得两类新的含三氟甲基的吲哚。我们发现，Friedel-Crafts反应条件下（小号） - ñ -叔丁基亚-3,3,3- trifluoroacetaldimine（1）发生反应容易用的吲哚衍生物，得到目标的3-取代的产品，而LDA促进的反应进行排他性在2位。我们证明这两种方法都具有广泛的底物范围，高化学收率和非对映选择性，这使得这些反应易于用于直接制备含有手性CF的生物学上感兴趣的化合物3 CH（NH 2）和吲哚基。提出了解释立体化学偏爱模式的机械原理。
• Discovery of a new class of valosine containing protein (VCP/P97) inhibitors for the treatment of colorectal cancer
  作者：Xueyuan Wang、Tiantian Wen、Hang Miao、Wenjiao Hu、Meng Lei、Yongqiang Zhu

  DOI：10.1016/j.bmc.2022.117050

  日期：2022.11

  of novel p97 inhibitors were designed, synthesized and biologically assayed. Based on the enzymatic results, structure–activity relationships (SAR) were discussed in detail. Some potent compounds were further evaluated to inhibit the proliferation of CRC cell lines HCT-116. The results showed that some compounds were active against CRC cell lines with IC50 values of less than 1 μM. Among the screened

  结直肠癌（CRC）是一种常见的消化道恶性肿瘤，是全球第三大癌症相关死亡病例。含有缬氨酸的蛋白质 (VCP/p97) 是 AAA ATPase 家族的成员，在泛素介导的错误折叠蛋白质降解中起重要作用。研究表明，p97在结直肠癌中过表达，是一个潜在的治疗靶点。在此，设计、合成和生物学测定了一系列新型 p97 抑制剂。基于酶促结果，详细讨论了构效关系 (SAR)。一些有效的化合物被进一步评估以抑制 CRC 细胞系 HCT-116 的增殖。结果表明，某些化合物对 CRC 细胞系具有活性，IC为 50值小于 1 μM。在筛选的化合物中，化合物10表现出良好的微粒体稳定性、药代动力学特性，并且对 HCT-116 细胞系 (0.4 μM) 表现出很强的抗增殖活性。此外，化合物10在人 CRC (HCT-116) 小鼠异种移植模型中表现出强大的体内抗癌功效。