2-(6-甲氧基-1H-吲哚-3-基)-2-氧代乙酸甲酯 | 408354-40-5

• 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
• 中文名称: 2-(6-甲氧基-1H-吲哚-3-基)-2-氧代乙酸甲酯
• 中文别名: 6-甲氧基-ALPHA-氧代-1H-吲哚-3-乙酸甲酯
• 英文名称: methyl 6-methoxyindolyl-3-glyoxylate
• 英文别名: 6-methoxy-1-methyl-α-oxo-1H-indole-3-acetic acid methyl ester；6-methoxy-α-oxo-1H-indole-3-acetic acid methyl ester；Methyl 2-(6-methoxy-1H-indol-3-YL)-2-oxoacetate
• CAS: 408354-40-5
• 化学式: C₁₂H₁₁NO₄
• 分子量: 233.224
• InChiKey: MIMMFXABEZXZPQ-UHFFFAOYSA-N

物化性质

• 沸点：
  418.2±25.0 °C(Predicted)
• 密度：
  1.314±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  68.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(6-甲氧基-1H-吲哚-3-基)-2-氧代乙酸甲酯 在 palladium on activated charcoal sodium hypophosphite 、 异丁酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 48.0h， 以74%的产率得到2-(6-甲氧基-1H-吲哚-3-基)乙酸甲酯
  参考文献：
  名称：

  Three oxidative metabolites of indole-3-acetic acid from Arabidopsis thaliana

  摘要：

  Three metabolites of indole-3-acetic acid (IAA), N-(6-hydroxyindol-3-ylacetyl)-phenylalanine (6-OH-IAA-Phe), N-(6-hydroxyindol-3-ylacetyl)-valine (6-OH-IAA-Val), and 1-O-(2-oxoindol-3-ylacetyl)-beta-D-glucopyranose (OxIAA-Glc), were found by a liquid chromatography-elect ro spray ionization-tandem mass spectrometry (LC-ESI-MS/MS)-based search for oxidative IAA metabolites during the vegetative growth of Arabidopsis. Their structures were confirmed by making a comparison of chromatographic characteristics and mass spectra between naturally occurring compounds and synthetic standards. An incorporation study using deuterium-labeled compounds showed that 6-OH-IAA-Phe and 6-OH-IAA-Val were biosynthesized from IAA-Phe and IAA-Val, respectively, which strongly suggested the formation of these;imino acid conjugates of IAA in plants. Both 6-OH-IAA-Phe and 6-OH-IAA-Val were inactive as auxins, as indicated by no significant root growth inhibition in Arabidopsis. Quantitative analysis demonstrated that OxIAA-Glc was present in the largest amount among the metabolites of IAA in Arabidopsis, suggesting that the conversion into OxIAA-Glc represents the main metabolic process regarding IAA in Arabidopsis. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.phytochem.2007.04.030
• 作为产物：
  描述：

  5-甲氧基吲哚 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 2-(6-甲氧基-1H-吲哚-3-基)-2-氧代乙酸甲酯
  参考文献：
  名称：

  Synthesis, determination of stereochemistry, and evaluation of new bisindole alkaloids from the myxomycete Arcyria ferruginea: An approach for Wnt signal inhibitor

  摘要：

  To determine the stereochemistry of dihydroarcyriarubin C (1), new bisindole alkaloid isolated from the myxomycete Arcyriajerruginea, cis- (2) and trans-dihydroarcyriarubin C (3) were synthesized. Comparison of their NMR characteristics allowed the trans stereochemistry of the natural product to be confirmed. Moreover, the Writ signal inhibitory activities of 2 and 3 were compared with that of arcyriaflavin C (4), which is a natural product containing a bond between C-2 and C-T. The cis-dihydroar-cyriarubin C (2) showed moderate inhibition of Wnt signal transcription, which suggests that bisindole frameworks might be useful as small-molecule Writ signal inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.033

文献信息

• Synthetic Approaches to Indolo[6,7-<i>a</i>]pyrrolo[3,4-<i>c</i>]carbazoles:  Potent Cyclin D1/CDK4 Inhibitors
  作者：Margaret M. Faul、Thomas A. Engler、Kevin A. Sullivan、John L. Grutsch、Marcella T. Clayton、Michael J. Martinelli、Joseph M. Pawlak、Michael LeTourneau、D. Scott Coffey、Steven W. Pedersen、Stanley P. Kolis、Kelly Furness、Sushant Malhotra、Rima S. Al-awar、James E. Ray

  DOI：10.1021/jo035606v

  日期：2004.4.1

  Synthesis of indolo[6,7-a]pyrrolo[3,4-c]carbazoles 1, a new class of cyclin D1/CDK4 inhibitors, by oxidation of the corresponding aryl indolylmaleimides 2, will be described. Two approaches to the synthesis of 2 were identified that required new methods for the synthesis of 7-substituted indole acetamides 3 and N-methyl (indol-7-yl)oxoacetates 6. The chemistry developed enabled introduction of functionality

  将描述通过相应芳基吲哚基马来酰亚胺2的氧化合成吲哚并[6，7- a ]吡咯并[3，4- c ]咔唑1，一种新型的细胞周期蛋白D1 / CDK4抑制剂。确定了两种合成2的方法，它们需要新的合成7-取代的吲哚乙酰胺3和N-甲基（吲哚-7-基）氧乙酸酯6的新方法。开发出的化学试剂能够在C 12和N 13处引入官能团（-OR，NR 2），从而促进了吲哚并咔唑平台的结构活性关系（SAR）评估。
• Methods and compounds for treating proliferative diseases
  申请人：——

  公开号：US20040048915A1

  公开（公告）日：2004-03-11

  The compounds disclosed herein are indolocarbazoles of Formula (I), which are potent CDK4 inhibitors, and are useful in the treatment of cell proliferative disorders, including cancer. Formula (I). 1

  本公开的化合物是式(I)的吲哚咔巴醌，它们是有效的CDK4抑制剂，并且在治疗细胞增殖性疾病，包括癌症方面具有用处。Formula (I).
• Dearomatization of tryptophols via a vanadium-catalyzed asymmetric epoxidation and ring-opening cascade
  作者：Long Han、Chuan Liu、Wei Zhang、Xiao-Xin Shi、Shu-Li You

  DOI：10.1039/c3cc47921h

  日期：——

  An enantioselective epoxidation of tryptophols followed by an intramolecular epoxide opening reaction was realized by chiral vanadium catalysts derived from C2 symmetric bis-hydroxamic acid (BHA) ligands. 3a-Hydroxyfuroindoline derivatives with up to 89% yield and 90% ee were obtained under mild reaction conditions.

  通过衍生自C2对称双异羟肟酸（BHA）配体的手性钒催化剂实现了对三酚的对映选择性环氧化，然后进行了分子内环氧化物开环反应。在温和的反应条件下获得了产率高达89％和ee达90％的3a-羟基呋喃二氢吲哚衍生物。
• Novel, potent and selective cyclin D1/CDK4 inhibitors: indolo[6,7-a]pyrrolo[3,4-c]carbazoles
  作者：Thomas A. Engler、Kelly Furness、Sushant Malhotra、Concha Sanchez-Martinez、Chuan Shih、Walter Xie、Guoxin Zhu、Xun Zhou、Scott Conner、Margaret M. Faul、Kevin A. Sullivan、Stanley P. Kolis、Harold B. Brooks、Bharvin Patel、Richard M. Schultz、Tammy B. DeHahn、Kashif Kirmani、Charles D. Spencer、Scott A. Watkins、Eileen L. Considine、Jack A. Dempsey、Catherine A. Ogg、Nancy B. Stamm、Bryan D. Anderson、Robert M. Campbell、Vasu Vasudevan、Michelle L. Lytle

  DOI：10.1016/s0960-894x(03)00461-x

  日期：2003.7

  The synthesis and CDK inhibitory properties of a series of indolo[6,7-a]pyrrolo[3,4-c]carbazoles is reported. In addition to their potent CDK activity, the compounds display antiproliferative activity against two human cancer cell lines. These inhibitors also effect strong G1 arrest in these cell lines and inhibit Rb phosphorylation at Ser780 consistent with inhibition of cyclin D1/CDK4.

  报道了一系列吲哚[6，7-a]吡咯并[3，4-c]咔唑的合成和CDK抑制性能。这些化合物除了具有强大的CDK活性外，还具有针对两种人类癌细胞系的抗增殖活性。这些抑制剂还影响这些细胞系中的强G1阻滞，并抑制Ser780处的Rb磷酸化，这与抑制细胞周期蛋白D1 / CDK4一致。
• Design and synthesis of (aza)indolyl maleimide-based covalent inhibitors of glycogen synthase kinase 3β
  作者：Zhimin Yang、Hui Liu、Botao Pan、Fengli He、Zhengying Pan

  DOI：10.1039/c8ob00642c

  日期：——

  reactive groups. Among these covalent inhibitors, compound 38b with a mild α-fluoromethyl amide reactive group emerges as a selective and covalent inhibitor against GSK-3β, effectively inhibits the phosphorylation of glycogen synthase and tau protein, and increases β-catenin's levels in living cells. In addition, compound 38b is highly permeable and not a substrate of P-glycoprotein.

  作为多种信号转导途径中的重要激酶，GSK-3β已成为化学探针发现和药物开发的有吸引力的靶标。与已开发的多种可逆抑制剂相比，GSK-3β的共价抑制剂明显缺乏。在这里，我们报告了通过优化非共价相互作用和反应性基团的一系列共价GSK-3β抑制剂的发现。在这些共价抑制剂中，具有轻度α-氟甲基酰胺反应性基团的化合物38b出现为针对GSK-3β的选择性共价抑制剂，可有效抑制糖原合酶和tau蛋白的磷酸化，并增加活细胞中β-catenin的水平。此外，化合物38b具有高渗透性，不是P的底物-糖蛋白。