ethyl 5-hydroxy-2-methylindole-3-carboxylate | 73975-59-4

• 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: ethyl 5-hydroxy-2-methylindole-3-carboxylate
• 英文别名: methyl 5-hydroxy-1,2-dimethyl-1H-indole-3-carboxylate；1,2-Dimethyl-5-hydroxyindol-3-carbonsaeuremethylester；methyl 5-hydroxy-1,2-dimethylindole-3-carboxylate
• CAS: 73975-59-4
• 化学式: C₁₂H₁₃NO₃
• mdl: MFCD00731606
• 分子量: 219.24
• InChiKey: JTPMSTFUJJHJRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  51.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 5-hydroxy-2-methylindole-3-carboxylate 在 盐酸 、 tin 、 lithium aluminium tetrahydride 、 硝酸 、 溶剂黄146 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 6.5h， 生成 3-(hydroxymethyl)-5-methoxy-1,2-dimethyl-1H-indole-4,7-dione
  参考文献：
  名称：

  Bexarotene prodrugs: Targeting through cleavage by NQO1 (DT-diaphorase)

  摘要：

  Bexarotene, a retinoid X receptor (RXR) agonist, is being tested as a potential disease modifying treatment for neurodegenerative conditions. To limit the peripheral exposure of bexarotene and release it only in the affected areas of the brain, we designed a prodrug strategy based on the enzyme NAD( P) H/quinone oxidoreductase (NQO1) that is elevated in neurodegenerative diseases. A series of indolequinones (known substrates of NQO1) was synthesized and coupled to bexarotene. Bexarotene-3(hydroxymethyl)-5-methoxy-1,2-dimethyl-1H-indole-4,7-dione ester 7a was cleaved best by NQO1. The prodrugs are not cleaved by esterase. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.003
• 作为产物：
  描述：

  乙酰乙酸甲酯 在 silica gel 作用下， 以 硝基甲烷 、 水 为溶剂， 反应 24.0h， 生成 ethyl 5-hydroxy-2-methylindole-3-carboxylate
  参考文献：
  名称：

  Bexarotene prodrugs: Targeting through cleavage by NQO1 (DT-diaphorase)

  摘要：

  Bexarotene, a retinoid X receptor (RXR) agonist, is being tested as a potential disease modifying treatment for neurodegenerative conditions. To limit the peripheral exposure of bexarotene and release it only in the affected areas of the brain, we designed a prodrug strategy based on the enzyme NAD( P) H/quinone oxidoreductase (NQO1) that is elevated in neurodegenerative diseases. A series of indolequinones (known substrates of NQO1) was synthesized and coupled to bexarotene. Bexarotene-3(hydroxymethyl)-5-methoxy-1,2-dimethyl-1H-indole-4,7-dione ester 7a was cleaved best by NQO1. The prodrugs are not cleaved by esterase. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.003

文献信息

• N–H Insertion reactions of rhodium carbenoids. Part 3.1 The development of a modified Bischler indole synthesis and a new protecting-group strategy for indoles
  作者：Katherine E. Bashford、Anthony L. Cooper、Peter D. Kane、Christopher J. Moody、Sendogagounder Muthusamy、Elizabeth Swann

  DOI：10.1039/b202666j

  日期：2002.7.11

  A modified version of the Bischler indole synthesis has been developed in which the key step is the N–H insertion reaction of rhodium carbene intermediates derived from α-diazo-β-ketoesters with anilines. Thus N-methylanilines 1 react with diazoketoesters 2 in the presence of dirhodium(II) acetate to give (N-arylamino)ketones 3, cyclisation of which using boron trifluoride–ethyl acetate or acidic ion exchange resin gives the indoles 4. In order to extend this method to the synthesis of N-unsubstituted indoles, a new protecting group strategy for indoles was developed. In this, anilines are reacted with α,β-unsaturated-esters or -sulfones to give the conjugate addition products 6 and 9, cyclisation of which gives indoles 8 and 11. The N-(2-ethoxycarbonylethyl)- and -(2-sulfonylethyl)- protecting groups are readily removed from indoles 8 and 11 by treatment with base.

  一种改进的Bischler吲哚合成方法已被开发，其中关键步骤是铑卡宾中间体从α-重氮-β-酮酯与苯胺的N-H插入反应。因此，N-甲基苯胺1与重氮酮酯2在二铑(II)醋酸盐存在下反应生成(N-芳氨基)酮3，使用三氟化硼-乙酸乙酯或酸性离子交换树脂进行环化反应得到吲哚4。为了将这种方法扩展到N-未取代的吲哚的合成，开发了一种新的吲哚保护基团策略。在此过程中，苯胺与α,β-不饱和酯或砜反应生成共轭加成产物6和9，其环化反应生成吲哚8和11。N-(2-乙氧羰基乙基)- 和 -(2-砜乙基)- 保护基团通过用碱处理从吲哚8和11中容易地去除。
• Synthesis and Pharmacology of Benzoxazines as Highly Selective Antagonists at M₄ Muscarinic Receptors
  作者：Thomas M. Böhme、Corinne E. Augelli-Szafran、Hussein Hallak、Thomas Pugsley、Kevin Serpa、Roy D. Schwarz

  DOI：10.1021/jm011116o

  日期：2002.7.1

  102807 (41) as being the most selective synthetic M(4) muscarinic antagonist identified to date. Synthesized analogues of 41 showed no improvement in affinity and selectivity at that time. However, several newly synthesized compounds exhibit a 7-fold higher affinity at M(4) receptors and demonstrate a selectivity of at least 100-fold over all other muscarinic receptor subtypes. For example, compound

  以前，我们在PD 102807（41）上报道其为迄今为止鉴定出的最具选择性的合成M（4）毒蕈碱拮抗剂。当时合成的41类似物没有显示亲和力和选择性的改善。但是，几种新合成的化合物在M（4）受体上显示出7倍更高的亲和力，并且比所有其他毒蕈碱受体亚型表现出至少100倍的选择性。例如，化合物28对M（4）受体显示pK（i）= 9.00的亲和力，对M（1）/ M（4）= 13183-fold，M（2）/ M（4）= 339倍，M（3）/ M（4）= 151倍和M（5）/ M（4）= 11220倍。尚未针对任何合成毒蕈碱拮抗剂或天然M（4）拮抗剂如M（4）选择性东部绿曼巴蛇毒MT3（M（4）pK（b）= 8.7）报道过这种高选择性和高亲和力。 ，M（1）/ M（4）= 40倍，M（2）/ M（4）>或= 500倍，M（3）/ M（4）>或= 500倍，以及M（5）/ M（4）>或= 500倍）。衍生物
• Synthesis of the new ring system 2-oxo-[1,4]oxazino[3,2-e]indole, heteroanalogue of Angelicin
  作者：Paola Barraja、Patrizia Diana、Alessandra Montalbano、Annamaria Martorana、Anna Carbone、Girolamo Cirrincione

  DOI：10.1016/j.tetlet.2009.05.007

  日期：2009.7

  A convenient synthesis of the 2-oxo-[1,4]oxazino[3,2-e]indole ring system, an heteroanalogue of Angelicin, is reported. Our synthetic approach consisted of the annelation of the oxazine ring on the indole moiety using 4-amino-5-hydroxy indoles as building blocks. The antiproliferative activity of the new compounds either in the dark or under UVA irradiation was investigated.

  据报道，方便合成2-氧代-[1,4]恶嗪基[3,2- e ]吲哚环系统，即安吉利辛的杂类似物。我们的合成方法包括使用4-氨基-5-羟基吲哚作为结构单元，在吲哚部分上恶嗪环脱环。研究了新化合物在黑暗中或在UVA照射下的抗增殖活性。
• Photoinduced Release of Fluorescent Probe in the Presence of Target DNA: Synergetic Effect of Two Types of Oligonucleotides with Indolequinone–Coumarin Conjugate and Flavin Photosensitizer
  作者：Kazuhito Tanabe、Yukihiro Tachi、Arimichi Okazaki、Sei-ichi Nishimoto

  DOI：10.1246/cl.2006.938

  日期：2006.8

  We have synthesized and evaluated two types of functionalized oligodeoxynucleotides (ODNs) that can release a fluorescent coumarin probe via co-hybridization with a target DNA base sequence and subsequent photoirradiation. Photoirradiation of flavin-bearing ODN in the presence of a counterpart ODN with indolequinone–coumarin conjugate and a target complementary DNA strand gave rise to the efficient release of coumarin with a multiple turnover as a result of intermolecular flavin-photosensitized reduction of indolequinone–coumarin conjugate, while the release of coumarin was considerably suppressed in the absence of the target DNA. Concomitant with this photoreaction, we could observe intense fluorescence emission from the sample solution photoirradiated with the target DNA, but weak fluorescence from a control solution without the target DNA.

  我们合成并评估了两种功能化寡去氧核苷酸（ODN），它们可以通过与目标 DNA 碱基序列共杂交和随后的光照射释放出荧光香豆素探针。在含有吲哚醌-香豆素共轭物的对应 ODN 和目标互补 DNA 链存在的情况下，对含有黄素的 ODN 进行光照射，由于分子间黄素对吲哚醌-香豆素共轭物的光敏还原作用，香豆素被有效地释放出来，且具有多次周转。在发生这种光反应的同时，我们可以观察到经过目标 DNA 光照射的样品溶液发出强烈的荧光，而没有目标 DNA 的对照溶液则发出微弱的荧光。
• Preparation and fluorescence properties of fluorophore-labeled avidin–biotin system immobilized on Fe3O4 nanoparticles through functional indolequinone linker
  作者：Nao Hirata、Kazuhito Tanabe、Asako Narita、Kazuo Tanaka、Kensuke Naka、Yoshiki Chujo、Sei-ichi Nishimoto

  DOI：10.1016/j.bmc.2009.04.048

  日期：2009.6

  We prepared and characterized a new class of fluorophore-labeled magnetic nanoparticles (MNPs) possessing a hypoxia-responsive unit to construct a hypoxia-selective emission system. The indolequinone derivative as a hypoxia-response unit bearing biotin was synthesized and immobilized on Fe3O4 MNP. Subsequent complexation of this functionalized MNP with fluorescein-labeled avidin formed fluorophore-labeled nanoparticles (AF-QB@MNP). The fluorescence intensity of AF-QB@MNP was suppressed because of the adjacent quenching function of the indolequinone moiety and MNP. Upon hypoxic treatment by NADPH: cytochrome P450 reductase, AF-QB@MNP was activated to liberate a fluorescence unit, leading to the significant enhancement of fluorescence emission, while a smaller enhancement in fluorescence emission occurred upon aerobic treatment. The AF-QB@MNP has a indispensable properties as a fluorescent probe for imaging of disease relevant hypoxic microenvironments. (C) 2009 Elsevier Ltd. All rights reserved.