(1H-indol-3-yl)(3,4,5-trimethoxyphenyl)methanone | 896462-39-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (1H-indol-3-yl)(3,4,5-trimethoxyphenyl)methanone
• 英文别名: 3-(3',4',5'-Trimethoxybenzoyl)indole；1H-indol-3-yl-(3,4,5-trimethoxyphenyl)methanone
• CAS: 896462-39-8
• 化学式: C₁₈H₁₇NO₄
• 分子量: 311.337
• InChiKey: IWZBDBYOZDTTCS-UHFFFAOYSA-N

物化性质

• 熔点：
  174-176 °C(Solv: dichloromethane (75-09-2); methanol (67-56-1))
• 沸点：
  526.9±50.0 °C(Predicted)
• 密度：
  1.235±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  60.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1H-indol-3-yl)(3,4,5-trimethoxyphenyl)methanone 在 氧气 、 palladium diacetate 、 potassium carbonate 、 三甲基乙酸 作用下， 反应 30.0h， 以67%的产率得到2,3,4-trimethoxy-5H-indeno[1,2-b]indol-10-one
  参考文献：
  名称：

  Intramolecular oxidative coupling of 3-indolylarylketones with Pd(II)-catalysis under air: convenient access to indenoindolones

  摘要：

  A Pd-catalyzed method has been developed for the intramolecular oxidative coupling of 3-indolylarylketones under open air as terminal oxidant toward the synthesis of indeno[1,2-b]indol-10(5H)-ones. This reaction represents an intramolecular coupling with dual activation of C-H bonds for electron-deficient arenes, while such reactions are common for electron-rich arenes. Pd(II)-catalysis with pivalic acid as co-catalyst has been found to be crucial. The reaction undergoes without indole N-H-protection. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.05.076
• 作为产物：
  描述：

  [1-(benzenesulfonyl)indol-3-yl]-(3,4,5-trimethoxyphenyl)methanone 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 (1H-indol-3-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  4- and 5-Aroylindoles as Novel Classes of Potent Antitubulin Agents

  摘要：

  A novel series of 4- and 5-aroylindole derivatives was prepared and evaluated for antitumor activity. Several compounds showed excellent antiproliferative activity as inhibitors of tubulin polymerization. Compounds 13, 14, 15, and 18, with IC50 values of 1.9, 1.1, 1.2, and 1.8 mu M, respectively, exhibited more potent inhibition of tubulin polymerization than colchicine. They also displayed antiproliferative activity, with IC50 values ranging from 10 to 43 nM in a variety of human cell lines from different organs.

  DOI：

  10.1021/jm070557q

文献信息

• Palladium catalyzed addition of arylboronic acid or indole to nitriles: synthesis of aryl ketones
  作者：Tuluma Das、Amarnath Chakraborty、Amitabha Sarkar

  DOI：10.1016/j.tetlet.2014.11.009

  日期：2014.12

  Aryl ketones can be synthesized conveniently by a palladium catalyzed addition of arylboronic acid to nitriles in aqueous triflic acid. This catalytic system was extended to the addition of unprotected indoles to nitriles under a slightly modified condition to produce 3-acyl indoles in good yields.

  芳基酮可以通过在三氟甲磺酸水溶液中钯催化将芳基硼酸加成到腈中来方便地合成。该催化体系扩展到在稍加修饰的条件下向腈中加入未保护的吲哚，以高收率生产3-酰基吲哚。
• ARYL HYDROCARBON RECEPTOR MODULATOR
  申请人：Ariagen, Inc.

  公开号：US20190307731A1

  公开（公告）日：2019-10-10

  Disclosed is an aryl hydrocarbon receptor modulator of formula (I), and a pharmaceutically acceptable salt thereof, wherein R′ is H, CN, CH 2 (OH)R 0 , C m H 2m+1 , C n H 2n-1 , C n H 2n-3 , two R a are independently H or two R a together form ═O or ═N—W 3 —R 1 ; A is a C 6 to C 10 aromatic ring unsubstituted or substituted with 1 to 3 R, or a C 2 -C 10 heteroaromatic ring interrupted by 1 to 5 heteroatoms selected from N, O, and S or a 4 to 7 membered nonaromatic heterocyclic ring containing C═N and interrupted by 1 to 3 heteroatoms selected from N, O, and S, with either one unsubstituted or substituted with 1 to 3 R; Q is R, or is a C 6 to C 10 aromatic ring or a C 2 to C 10 heteroaromatic ring unsubstituted or substituted with 1 to 3 R and interrupted by 1 to 5 heteroatoms selected from N, O, and S; and R is R c which is C-attached or R N which is N-attached. The compounds of formula (I) of the present invention can regulate AhR activity, and can be used to inhibit the growth of cancer cells and inhibit the metastasis and invasion of tumor cells.

  本发明揭示了一种化学式（I）的芳香烃受体调节剂及其药用可接受盐，其中R′为H、CN、CH2（OH）R0、CmH2m+1、CnH2n-1、CnH2n-3，两个Ra独立地为H或两个Ra共同形成═O或═N—W3—R1；A为未取代或取代1至3个R的C6至C10芳香环，或由N、O和S中选择的1至5个杂原子中断的C2-C10杂芳环，或含有C═N并由N、O和S中选择的1至3个杂原子中断的4至7个成员的非芳杂环，其中一个未取代或取代1至3个R；Q为R，或者是未取代或取代1至3个R并由N、O和S中断的C6至C10芳香环或C2至C10杂芳环；R为C-连接的Rc或N-连接的RN。本发明的化合物可以调节AhR活性，可用于抑制癌细胞的生长，以及抑制肿瘤细胞的转移和侵袭。
• ZrCl₄-Mediated Regio- and Chemoselective Friedel–Crafts Acylation of Indole
  作者：Sankar K. Guchhait、Maneesh Kashyap、Harshad Kamble

  DOI：10.1021/jo200561f

  日期：2011.6.3

  method for regio- and chemoselective Friedel–Crafts acylation of indole using acyl chlorides in the presence of ZrCl4 has been discovered. It minimizes/eliminates common competing reactions that occur due to high and multiatom-nucleophilic character of indole. In this method, a wide range of aroyl, heteroaroyl alkenoyl, and alkanoyl chlorides undergo smooth acylation with various indoles without NH

  发现了在ZrCl 4存在下使用酰氯对吲哚进行区域选择性和化学选择性Friedel-Crafts酰化的有效方法。它最小化/消除了由于吲哚的高原子和多原子亲核特性而发生的常见竞争反应。在这种方法中，广泛的芳酰基，杂芳基链烯酰基和链烷酰氯与各种没有吲哚保护的吲哚进行平滑的酰化反应，并以高收率或高收率得到了3-酰化吲哚。
• Collective Synthesis of 3-Acylindoles, Indole-3-carboxylic Esters, Indole-3-sulfinic Acids, and 3-(Methylsulfonyl)indoles from Free (N–H) Indoles via Common <i>N</i>-Indolyl Triethylborate
  作者：Zhi-Wei Zhang、Hong Xue、Hailing Li、Huaiping Kang、Juan Feng、Aijun Lin、Shouxin Liu

  DOI：10.1021/acs.orglett.6b01970

  日期：2016.8.5

  A general and direct C3 functionalization of free (N–H) indoles with readily available electrophiles such as acid chlorides, chloroformates, thionyl chloride, and methylsulfonyl chloride via a common N-indolyl triethylborate intermediate is reported. The reaction proceeds smoothly under mild conditions in up to 93% yield. Indoles with substituents at the C2, C4, C5, C6, and C7 positions are well tolerated

  据报道，通过常见的N-吲哚基三乙基硼酸酯中间体，可以利用容易获得的亲电子试剂（如酰氯，氯甲酸酯，亚硫酰氯和甲基磺酰氯）对游离（NH）吲哚进行一般和直接的C3功能化。反应在温和条件下平稳进行，收率高达93％。在C2，C4，C5，C6和C7位置带有取代基的吲哚具有良好的耐受性。各种重要的3-acylindoles，吲哚-3-羧酸酯，吲哚-3-亚磺酸和3-（甲基磺酰基）吲哚的易于获得证明了该方法的高度相容性和实用性。
• 4-(3-Phenyl-4-(3,4,5-trimethoxybenzoyl)-1<i>H</i>-pyrrol-1-yl)benzenesulfonamide, a Novel Carbonic Anhydrase and Wnt/β-Catenin Signaling Pathway Dual-Targeting Inhibitor with Potent Activity against Multidrug Resistant Cancer Cells
  作者：Domiziana Masci、Michela Puxeddu、Laura Di Magno、Michele D’Ambrosio、Anastasia Parisi、Marianna Nalli、Ruoli Bai、Antonio Coluccia、Pietro Sciò、Viviana Orlando、Sara D’Angelo、Stefano Biagioni、Andrea Urbani、Ernest Hamel、Alessio Nocentini、Serena Filiberti、Marta Turati、Roberto Ronca、Joanna Kopecka、Chiara Riganti、Cinzia Fionda、Rosa Bordone、Giorgia Della Rocca、Gianluca Canettieri、Claudiu T. Supuran、Romano Silvestri、Giuseppe La Regina

  DOI：10.1021/acs.jmedchem.3c01424

  日期：2023.11.9

  panel of cancer cells, including colorectal cancer and triple-negative breast cancer cells, was effective against the NCI/ADR-RES DOX-resistant cell line, and restored the sensitivity to doxorubicin (DOX) in HT29/DX and MDCK/P-gp cells. Compound 15 is a novel dual-targeting compound with activity against hCA and Wnt/β-catenin. It thus has a broad targeting spectrum and is an anticancer agent with specific

  我们合成了新的吡咯和吲哚衍生物作为人碳酸酐酶 (hCA) 抑制剂，具有抑制 Wnt/β-catenin 信号通路的潜力。 N 1-(4-磺酰氨基苯基)和3-(3,4,5-三甲氧基苯基)取代基的存在对于强hCA抑制剂是必需的。最有效的 hCA XII 抑制剂15 ( K i = 6.8 nM) 抑制 Wnt/β-catenin 信号通路及其靶基因 MYC、Fgf20 和 Sall4，并表现出典型的细胞凋亡标志物、裂解的聚（ADP-核糖）聚合酶、和裂解的 caspase-3。化合物15对一组癌细胞（包括结直肠癌和三阴性乳腺癌细胞）的活力表现出强烈的抑制作用，可有效对抗 NCI/ADR-RES DOX 耐药细胞系，并恢复对阿霉素 (DOX) 的敏感性。 HT29/DX 和 MDCK/P-gp 细胞。化合物15是一种新型双靶向化合物，具有抗 hCA 和 Wnt/β-catenin 活性。因此，它具有广泛的靶向谱，是一种在