2-[5-甲氧基-2-甲基-1-(4-甲基苯甲酰基)吲哚-3-基]乙酸 | 16401-76-6

• 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-[5-甲氧基-2-甲基-1-(4-甲基苯甲酰基)吲哚-3-基]乙酸
• 英文名称: 2-(5-methoxy-2-methyl-1-(4-methylbenzoyl)-1H-indol-3-yl)acetic acid
• 英文别名: 2-[5-methoxy-2-methyl-1-(4-methylbenzoyl)indol-3-yl]acetic Acid
• CAS: 16401-76-6
• 化学式: C₂₀H₁₉NO₄
• 分子量: 337.375
• InChiKey: ASIGZZOVSCNZDW-UHFFFAOYSA-N

物化性质

• 熔点：
  150-151 °C(Solv: acetone (67-64-1); water (7732-18-5))
• 沸点：
  488.1±45.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  68.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  异丁胺 、 2-[5-甲氧基-2-甲基-1-(4-甲基苯甲酰基)吲哚-3-基]乙酸 在 二氧化碳 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 48.0h， 以84%的产率得到
  参考文献：
  名称：

  通过原位可逆结构变化调节微凝胶中硼酸的催化作用

  摘要：

  固定在聚合物微凝胶中的硼酸的催化作用可以通过用 N 2 /CO 2气体鼓泡来调节，在某些情况下还可以通过添加葡萄糖来调节，使其催化活性与均匀分散的相应游离硼酸单体的催化活性相当甚至更好。解决方案，更重要的是，使这些含硼酸的聚合物微凝胶能够催化可能扩展用途的替代反应。这些含硼酸的微凝胶作为有机硼酸催化剂的这种增强的催化功能似乎是通过原位实现的可逆的结构变化。为了更好地理解催化过程，已经对模型硼酸催化的aza-Michael加成、醛醇、酰胺化和[4 + 2]环加成反应进行了动力学研究。

  DOI：

  10.1039/c9ra10541g
• 作为产物：
  描述：

  5-甲氧基-2-甲基-3-吲哚乙酸 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 trimethyl-tin hydroxide 、 三乙胺 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 1.0h， 生成 2-[5-甲氧基-2-甲基-1-(4-甲基苯甲酰基)吲哚-3-基]乙酸
  参考文献：
  名称：

  Straightforward protocol for the efficient synthesis of varied N1-acylated (aza)indole 2-/3-alkanoic acids and esters: optimization and scale-up

  摘要：

  A library of approximately 40 N-1-acylated (aza)indole alkanoic esters and acids was prepared employing a microwave-assisted approach. The optimized synthetic route allows for parallel synthesis, variation of the indole substitution pattern, and high overall yield. Additionally, the procedure has been scaled up to yield multi-gram amounts of preferred indole compounds, e.g.: 2'-des-methyl indomethacin 2. The reported compounds were designed as biomedical tools for primary and secondary in vitro and in vivo studies at relevant molecular targets. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2012.08.044

文献信息

• [EN] INDOMETHACIN ANALOGS FOR THE TREATMENT OF CASTRATE-RESISTANT PROSTATE CANCER<br/>[FR] ANALOGUES DE L'INDOMÉTACINE DESTINÉS AU TRAITEMENT DU CANCER DE LA PROSTATE RÉSISTANT À LA CASTRATION
  申请人：UNIV VANDERBILT

  公开号：WO2013059245A1

  公开（公告）日：2013-04-25

  Provided are compositions for inhibiting a biological activity of an aldoketo reductase family 1, member C3 (AKR1 C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1 C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.

  提供了用于抑制醛酮还原酶家族1成员C3（AKR1 C3）多肽的生物活性的组合物。在某些实施例中，这些组合物是吲哚美酸衍生物，是AKR1 C3特异性抑制剂。还提供了生产所述吲哚美酸衍生物的方法，这些衍生物基本缺乏环氧合酶抑制活性，但具有AKR1C3抑制活性，以及抑制AKR1C3多肽生物活性的方法，以及治疗受试者前列腺肿瘤的方法。
• INDOMETHACIN ANALOGS FOR THE TREATMENT OF CASTRATE-RESISTANT PROSTATE CANCER
  申请人：Vanderbilt University

  公开号：US20140371261A1

  公开（公告）日：2014-12-18

  Provided are compositions for inhibiting a biological activity of an aldoketo reductase family 1, member C3 (AKR1 C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1 C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.

  提供了一些用于抑制醛酮还原酶家族1成员C3（AKR1 C3）多肽生物活性的组合物。在某些实施例中，这些组合物是AKR1 C3特异性抑制剂的吲哚美辛衍生物。还提供了制备所述吲哚美辛衍生物的方法，这些方法基本上缺乏环氧合酶抑制活性，但具有AKR1C3抑制活性，以及抑制AKR1C3多肽生物活性的方法和治疗受试者的前列腺肿瘤的方法。
• Indomethacin analogs for the treatment of castrate-resistant prostate cancer
  申请人：Vanderbilt University

  公开号：US10398678B2

  公开（公告）日：2019-09-03

  Provided are compositions for inhibiting a biological activity of an aldo-keto reductase family 1, member C3 (AKR1C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.

  本文提供了用于抑制醛酮还原酶家族 1 成员 C3（AKR1C3）多肽生物活性的组合物。在某些实施方案中，这些组合物是 AKR1C3 特异性抑制剂的吲哚美辛衍生物。还提供了生产所公开的基本上缺乏环氧化酶抑制活性但具有AKR1C3抑制活性的吲哚美辛衍生物的方法、抑制AKR1C3多肽生物活性的方法以及治疗受试者前列腺肿瘤的方法。
• Modulation of MRP-1-Mediated Multidrug Resistance by Indomethacin Analogues
  作者：Claudia Rosenbaum、Sonja Röhrs、Oliver Müller、Herbert Waldmann

  DOI：10.1021/jm0499099

  日期：2005.2.1

  Multidrug resistance (MDR) is a major limiting factor in the development and application of drug candidates. MDR caused by MRP-1 is known to be modulated by the nonsteroidal antiinflammatory drug indomethacin. We have synthesized and biologically evaluated a library of indomethacin analogues. The indomethacin-derived compound library was synthesized employing the Fischer-indole synthesis as the key transformation and making use of a "resin-capture-release" strategy. Sixty representative members of the library were evaluated in a cell biological cytotoxicity assay employing the MRP-1 expressing human glioblastoma cell line T98G as a model system. Nine of the 60 tested derivatives increased the doxorubicin-mediated cytotoxicity at a comparable or higher level than indomethacin itself. Analysis of these derivatives revealed an interesting structure-function relationship. Most remarkably, two substances increased the toxicity, when doxorubicin was used at clinically relevant low concentrations, at a higher degree than indomethacin.
• SOLID COMPOSITION FOR CONTROLLED RELEASE OF IONIZABLE ACTIVE AGENTS WITH POOR AQUEOUS SOLUBILITY AT LOW pH AND METHODS OF USE THEREOF
  申请人：Ramani Chandir

  公开号：US20100151019A1

  公开（公告）日：2010-06-17

  A novel solid composition and methods for making and using the solid composition are provided. The solid composition comprises: (a) at least one active agent with a solubility of less than about 0.3 mg/ml in an aqueous solution with a pH of at most about 6.8 at a temperature of about 37° C.; and (b) a hydrophilic polymer matrix composition comprising: i) a hydrophilic polymer selected from the group consisting of METHOCEL™, POLYOX™ WSR 1105 and combinations thereof; and optionally ii) a hydrophobic polymer selected from the group consisting of Ethocel 20 premium; and (c) an alkalizer selected from the group consisting of calcium carbonate, magnesium oxide heavy and sodium bicarbonate; wherein the composition provides at least about 70% release of the active between about 7 to about 12 hours following oral administration.