methyl 5-methoxy-3-((3,4,5-trimethoxyphenyl)thio)-1H-indole-2-carboxylate

• 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: methyl 5-methoxy-3-((3,4,5-trimethoxyphenyl)thio)-1H-indole-2-carboxylate
• 英文别名: methyl 5-methoxy-3-(3,4,5-trimethoxyphenyl)sulfanyl-1H-indole-2-carboxylate
• 化学式: C₂₀H₂₁NO₆S
• 分子量: 403.456
• InChiKey: ACDKXOCMVBVHIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 5-methoxy-3-((3,4,5-trimethoxyphenyl)thio)-1H-indole-2-carboxylate 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 以99%的产率得到methyl 5-methoxy-3-(3,4,5-trimethoxyphenylsulfinyl)-1H-indole-2-carboxylate
  参考文献：
  名称：

  New Arylthioindoles and Related Bioisosteres at the Sulfur Bridging Group. 4. Synthesis, Tubulin Polymerization, Cell Growth Inhibition, and Molecular Modeling Studies

  摘要：

  New arylthioindoles along with the corresponding ketone and methylene compounds were potent tubulin assembly inhibitors. As growth inhibitors of MCF-7 cells, sulfur derivatives were superior or sometimes equivalent to the ketones, while methylene derivatives were substantially less effective. Esters 24, 27-29, 36, 39, and 41 showed similar to 50% of inhibition oil human HeLa and HCT116/chr3 cells at 0.5 mu M, and these compounds inhibited the growth of HEK, M 14, and U937 cells with IC50'S ill the 78220 nM range. While murine macrophage J744.1 cell growth was significantly less affected (20% at higher concentrations), four other nontransformed cell lines remained sensitive to these esters. The effect of drug treatment oil cell morphology was examined by time-lapse microscopy. In a protocol set up to evaluate toxicity on the Saccharomyces cerevisiae BY4741 wild type strain, compounds 24 and 54 strongly reduced cell growth, and 29, 36, and 39 also showed significant inhibition.

  DOI：

  10.1021/jm900016t
• 作为产物：
  描述：

  O-ethyl S-(3,4,5-trimethoxyphenyl)carbonodithioate 在 manganese(IV) oxide 、 碘 、 氧气 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 51.0h， 生成 methyl 5-methoxy-3-((3,4,5-trimethoxyphenyl)thio)-1H-indole-2-carboxylate
  参考文献：
  名称：

  苯甲醚中碘/锰催化脱氢氧化偶联吲哚的亚磺酰基化

  摘要：

  该方案描述了碘/锰催化体系，用于吲哚中吲哚与硫醇的脱氢氧化偶联反应。特别是，苯甲醚的双重作用已首先通过形成氧离子中间体以加速产物的产生而证明其作为溶剂和促进剂。在需氧温和的反应条件下很容易构建一系列的亚磺酰基吲哚。此外，制备抗癌和抗艾滋病药物的成就证明了这种方法的实用性。机制研究揭示了可能的替代途径，并且单电子转移过程也参与了这一转变。

  DOI：

  10.1002/adsc.202000291

文献信息

• Sodium Iodide (NaI)-Catalyzed Cross-Coupling for C−S Bond Formation via Oxidative Dehydrogenation: Cheap, Direct Access to Unsymmetrical Aryl Sulfides
  作者：Hui-Hong Wang、Tao Shi、Wei-Wei Gao、Yong-Qiang Wang、Jun-Fang Li、Yi Jiang、Yong Sheng Hou、Chen Chen、Xue Peng、Zhen Wang

  DOI：10.1002/asia.201701163

  日期：2017.10.18

  yields with high regioselectivity from readily available aromatic compounds and aryl/alkyl thiols, even on gram scale. To demonstrate the practicability of this reaction, two bioactive compound skeletons were synthesized in good yields. This method can also be used to late‐stage modification of curcumin.

  在空气中已经开发出一种简单实用的NaI催化的芳烃直接CH磺酰化方法。在该反应中，即使是按克规模，也从容易获得的芳族化合物和芳基/烷基硫醇以中等至优异的产率和高的区域选择性获得芳基硫化物。为了证明该反应的实用性，以高收率合成了两个生物活性化合物骨架。此方法也可用于姜黄素的后期修饰。
• Catalytic Synthesis of 3-Thioindoles Using Bunte Salts as Sulfur Sources under Metal-Free Conditions
  作者：Hong Qi、Tongxin Zhang、Kefeng Wan、Meiming Luo

  DOI：10.1021/acs.joc.6b00636

  日期：2016.5.20

  An efficient catalytic method for the synthesis of 3-thioindoles has been successfully developed, which uses odorless, stable, readily available crystalline Bunte salts as the sulfenylating agents, iodine as nonmetallic catalyst, and DMSO as both the oxidant and solvent. This method is practical and environmentally benign in terms of sulfur sources, catalyst, and solvent. The catalytic reaction is

  已成功开发出一种有效的催化方法，用于合成3-硫代吲哚，该方法使用无味，稳定，易得的结晶邦特盐作为亚磺化剂，使用碘作为非金属催化剂，并使用DMSO作为氧化剂和溶剂。就硫源，催化剂和溶剂而言，该方法是实用且对环境无害的。催化反应在吲哚的C3位置处具有选择性，并且可与多种底物相容，从而以良好或优异的收率得到所需的产物。
• [EN] ARYLTHIOINDOLE TUBULIN POLYMERIZATION INHIBITORS AND METHODS OF TREATING OR PREVENTING CANCER USING SAME<br/>[FR] INHIBITEURS DE LA POLYMERISATION DE LA TUBULINE DE TYPE ARYLTHIOINDOLE, ET PROCEDES POUR TRAITER OU PREVENIR UN CANCER AU MOYEN DE CES INHIBITEURS
  申请人：HUMAN SERVICES GOVERNMENT OF T

  公开号：WO2006041961A1

  公开（公告）日：2006-04-20

  The present invention features arylthioindole compounds, pharmaceutical compositions of arylthioindole compounds and methods of treating a patient suffering from cancer or inflammatory, cardiac, or helminthic diseases, the method comprising administering to a patient one or more arylthioindole compounds of the invention.

  本发明涉及芳基硫代吲哚化合物，芳基硫代吲哚化合物的药物组合物以及治疗患有癌症或炎症、心脏病或寄生虫病的患者的方法，该方法包括向患者施用本发明的一种或多种芳基硫代吲哚化合物。
• Arylthioindoles, Potent Inhibitors of Tubulin Polymerization
  作者：Gabriella De Martino、Giuseppe La Regina、Antonio Coluccia、Michael C. Edler、Maria Chiara Barbera、Andrea Brancale、Elizabeth Wilcox、Ernest Hamel、Marino Artico、Romano Silvestri

  DOI：10.1021/jm049360d

  日期：2004.12.1

  Several arylthioindoles had excellent activity as inhibitors both of tubulin polymerization and of the growth of MCF-7 human breast carcinoma cells. Methyl 3-[(3,4,5-trimethoxyphenyl)thio]-5-methoxy-1H-indole-2-carboxylate (21), the most potent derivative, showed IC(50) = 2.0 microM, 1.6 times more active than colchicine and about as active as combretastatin A-4 (CSA4). Compound 21 inhibited the growth

  几种芳基硫代吲哚作为微管蛋白聚合和MCF-7人乳腺癌细胞生长的抑制剂均具有出色的活性。最有效的衍生物3-[（3,4,5-三甲氧基苯基）硫代] -5-甲氧基-1H-吲哚-2-羧酸甲酯（21）的IC（50）= 2.0 microM，活性是其1.6倍秋水仙碱，其活性与康维他汀A-4（CSA4）差不多。化合物21在IC（50）= 13 nM时抑制了MCF-7细胞的生长。秋水仙碱和CSA4与这些细胞分别具有13 nM和17 nM IC（50）值。
• Chiral Phosphoric Acid‐Catalyzed Chemo‐ and Enantioselective N‐Alkylation of Indoles with Imines
  作者：Shuyuan Yang、Linger Li、Junling Zhao

  DOI：10.1002/adsc.202201077

  日期：2022.12.8

  A chemo- and enantioselective protocol for the N-alkylation of indoles with imines was developed. This process was catalyzed by a BINOL-derived phosphoric acid catalyst to give the corresponding acyclic aminals of indoles in 46–99% yields with 70–98% ee. The application of this method for the “late-stage” functionalization of a bioactive compound was performed with high efficency. The products showed

  开发了用亚胺对吲哚进行 N-烷基化的化学和对映选择性方案。该过程由 BINOL 衍生的磷酸催化剂催化，以 46-99% 的产率和 70-98% ee 得到相应的吲哚无环缩醛胺。该方法用于生物活性化合物“后期”功能化的应用效率很高。产品表现出良好的稳定性，并可以进行许多进一步的转化。