1-(4-甲氧基-1H-吲哚-3-基)乙酮 | 73260-12-5

• 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: 1-(4-甲氧基-1H-吲哚-3-基)乙酮
• 英文名称: 3-acetyl-4-methoxy-1H-indole
• 英文别名: 1-(4-Methoxy-1H-indol-3-yl)ethan-1-one；1-(4-methoxy-1H-indol-3-yl)ethanone
• CAS: 73260-12-5
• 化学式: C₁₁H₁₁NO₂
• 分子量: 189.214
• InChiKey: RESASAWFRNZNAI-UHFFFAOYSA-N

物化性质

• 熔点：
  113-115 °C(Solv: dichloromethane (75-09-2))
• 沸点：
  371.8±22.0 °C(Predicted)
• 密度：
  1.202±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-甲氧基-1H-吲哚-3-基)乙酮 在 sodium methylate 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.23h， 生成 ethyl 4-{1-[4-(trifluoromethyl)benzyl]-4-methoxy-1H-indol-3-yl}-2-hydroxy-4-oxobut-2-enoate
  参考文献：
  名称：

  Synthesis and biological evaluation of novel antiviral agents as protein–protein interaction inhibitors

  摘要：

  In continuation of our research efforts toward the identification and optimization for novel inhibitors of interaction between human immunodeficiency virus type 1 integrase and cellular cofactor LEDGF/p75, we designed and synthesized a new series of 4-benzylindole derivatives. Most of the title compounds proved to be able to block this protein-protein interaction (PPI), with a percentage ranging from 30% to 90% at 100 mu M. The most promising derivative was compound 10b showing IC50 value of 6.41 mu M. The main structure-activity relationships (SAR) are discussed and rationalized by docking studies.

  DOI：

  10.3109/14756366.2013.766609
• 作为产物：
  描述：

  4-甲氧基吲哚 、 N,N-二甲基乙酰胺 在 三氯氧磷 作用下， 反应 12.0h， 以89%的产率得到1-(4-甲氧基-1H-吲哚-3-基)乙酮
  参考文献：
  名称：

  小分子的微波辅助有机合成 (MAOS) 作为潜在的 HIV-1 整合酶抑制剂。

  摘要：

  Integrase (IN) 代表了开发针对人类免疫缺陷病毒 (HIV) 的抗病毒药物的临床验证目标。近年来，我们的研究组一直从事这种酶的结构功能研究和一些三维药效团模型的开发，从而鉴定了一系列有效的HIV-1整合酶链转移抑制剂。 INSTIs) 带有吲哚核。为了更好地了解构效关系 (SAR)，我们在此报告了一系列新型 1-H-苄基吲哚衍生物的设计和微波辅助合成。

  DOI：

  10.3390/molecules16086858

文献信息

• Structural Modification of Diketo Acid Portion in 1H-Benzylindole Derivatives HIV-1 Integrase Inhibitors
  作者：Stefania Ferro、Sara De Grazia、Laura De Luca、Maria Letizia Barreca、Zeger Debyser、Alba Chimirri

  DOI：10.3987/com-08-11573

  日期：——

  benzylindoldiketo acid (CHI-1043) acting as HIV-1 integrase strand transfer inhibitor. We herein report the synthesis of new structurally different compounds in which the 1,3-diketo acid moiety has been substituted with other functionalities. The synthesized derivatives were evaluated for their activity on the IN enzyme and in MT-4 cells but only 4-[l-(4-fluorobenzyl)-4-methoxy-1H-indol-3-yl)-3-hydroxyfuran-2(5H)-one

  我们之前的研究导致发现了一种非常有效的苄基吲哚酮酸 (CHI-1043) 作为 HIV-1 整合酶链转移抑制剂。我们在此报告了新的结构不同的化合物的合成，其中 1,3-二酮酸部分已被其他官能团取代。评估了合成的衍生物对 IN 酶和 MT-4 细胞的活性，但只有 4-[1-(4-fluorobenzyl)-4-methoxy-1H-indol-3-yl)-3-hydroxyfuran-2( 5H)-one (12) 可能通过生物转化为 CHI-1043 来强烈抑制 HIV-1。
• Searching for indole derivatives as potential mushroom tyrosinase inhibitors
  作者：Stefania Ferro、Giovanna Certo、Laura De Luca、Maria Paola Germanò、Antonio Rapisarda、Rosaria Gitto

  DOI：10.3109/14756366.2015.1029470

  日期：——

  enzyme. The obtained biological results demonstrated that compounds containing 4-fluorobenzyl moiety at N - 1 position of indole system showed the best activity. In addition, the role of the portion linked to the carbonyl group at C - 3 was discussed. A Lineweaver-Burk kinetic analysis of the most active indoles, CHI 1043 and derivative 4, showed a mixed-type inhibition in the presence of L-3,4-dihydroxyphenylalanine

  酪氨酸酶是自然界中广泛分布的一种含铜酶，参与黑色素的生物合成，其作用是保护皮肤免受紫外线伤害。人们对黑色素参与恶性黑色素瘤和其他致癌过程表现出极大的兴趣。这些现象鼓励了在治疗领域以及在食品和化妆品中用于防止褐变的酪氨酸酶抑制剂的研究。想法是筛选我们的“内部”数据库，以选择合适的先导化合物以发现潜在的药物抑制酶。所获得的生物学结果表明，在吲哚体系的N-1位含有4-氟苄基部分的化合物显示出最佳的活性。另外，还讨论了在C-3处与羰基连接的部分的作用。
• PHTHALAZINONES AND ISOQUINOLINONES AS ROCK INHIBITORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20150353505A1

  公开（公告）日：2015-12-10

  The present invention provides compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective ROCK inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating cardiovascular, smooth muscle, oncologic, neuropathologic, autoimmune, fibrotic, and/or inflammatory disorders using the same.

  本发明提供了公式（I）的化合物或其立体异构体，互变异构体或药学上可接受的盐，其中所有变量如此定义。这些化合物是选择性ROCK抑制剂。本发明还涉及包含这些化合物的制药组合物以及使用它们治疗心血管，平滑肌，肿瘤，神经病理，自身免疫，纤维化和/或炎症性疾病的方法。
• A refined pharmacophore model for HIV-1 integrase inhibitors: Optimization of potency in the 1H-benzylindole series
  作者：Laura De Luca、Maria Letizia Barreca、Stefania Ferro、Nunzio Iraci、Martine Michiels、Frauke Christ、Zeger Debyser、Myriam Witvrouw、Alba Chimirri

  DOI：10.1016/j.bmcl.2008.03.089

  日期：2008.5

  We report herein the development of a new three-dimensional pharmacophore model for HIV-1 integrase inhibitors which led to the discovery of some 4-[1-(4-fluorobenzyl)-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acids that are able to specifically inhibit the strand transfer step of integration at nanomolar concentration. The synthesis of the new designed molecules is also described. (c) 2008 Elsevier Ltd. All rights reserved.
• 4-[1-(4-Fluorobenzyl)-4-hydroxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid as a prototype to develop dual inhibitors of HIV-1 integration process
  作者：Laura De Luca、Rosaria Gitto、Frauke Christ、Stefania Ferro、Sara De Grazia、Francesca Morreale、Zeger Debyser、Alba Chimirri

  DOI：10.1016/j.antiviral.2011.07.005

  日期：2011.10

  In recent years several potent HIV-1 integrase (IN) inhibitors have been identified and after the successful clinical use of raltegravir, they have gained a definitive place in the treatment of HIV-1 infection. Yet, there is a continuous effort to design newer inhibitors that target different steps in the integration process. Furthermore, the increased understanding of IN structural biology has opened novel approaches to inhibit IN, such as targeting its multimerization or interaction with cellular cofactors. On these bases, we have concentrated our research on the identification of small molecules able to inhibit two different stages of the integration process: the IN strand-transfer phase and the IN-LEDGF/p75 interaction. We found that the 4-[1-(4-fluorobenzyl)-4-hydroxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (CHI-1043) is an interesting anti-HIV agent exhibiting dual inhibitory effects. This work has suggested the possibility of also constructing an integration dual inhibitor using a design-in strategy. (C) 2011 Elsevier B.V. All rights reserved.