dimethyl 1H-indole-3,5-dicarboxylate | 888319-94-6

• 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
• 英文名称: dimethyl 1H-indole-3,5-dicarboxylate
• 英文别名: dimethyl indole-3,5-dicarboxylate
• CAS: 888319-94-6
• 化学式: C₁₂H₁₁NO₄
• 分子量: 233.224
• InChiKey: ANGMRSFNYRSJQS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 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：

  dimethyl 1H-indole-3,5-dicarboxylate 在 1,4-二甲基哌嗪 、 N-氯代丁二酰亚胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二苯醚 、 甲苯 为溶剂， 生成 methyl 11-(4-aminobutylamino)-5-methyl-5H-indolo[2,3-b]quinoline-9-carboxylate
  参考文献：
  名称：

  11-氨基烷基氨基取代的5 H-吲哚并[2,3-b]喹啉的体外抗增殖活性；通过安装酯取代基改善新隐油菜素的活性

  摘要：

  摘要该研究文章描述了酯基对5-甲基-5 H-吲哚并[2,3- b ]喹啉（新隐油菜籽）衍生物的SAR研究中体外抗增殖活性的影响。从吲哚-3-羧酸酯和N开始合成C-2和/或C-9酯取代的新隐油松-带有酯基的甲基苯胺。在这些酯取代的新隐油松上，在C-11处进一步连接了多个氨基烷基氨基取代基，并通过改变C-11处的取代基以及A和/或D中酯基的位置进行了体外抗增殖测定新隐油环的环。结果表明，通过在C-9位引入酯取代基可以改善药物的抗增殖活性。其中，11-（3-氨基丙基氨基）-5-甲基-5 H-吲哚并[2,3 - b ]喹啉-9-羧酸酯（8b）是最有效的IC 50试剂。0.044μM对人白血病MV4-11细胞株的抗 还描述了药剂在癌细胞系和正常细胞系之间的选择性细胞毒性。二甲基11-（3-氨基丙基氨基）-5-甲基-5 H-吲哚并[2,3 - b ]喹啉-2,9-二羧酸盐（9a）对人结肠癌细胞系HCT

  DOI：

  10.1007/s00044-012-0443-x
• 作为产物：
  描述：

  (Z)-methyl 4-((3-methoxy-3-oxoprop-1-en-1-yl)amino)benzoate 在 copper diacetate 、 potassium carbonate 、 palladium dichloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 以61%的产率得到dimethyl 1H-indole-3,5-dicarboxylate
  参考文献：
  名称：

  分子氧作用下芳族伯胺和烯烃的钯催化氧化偶联：（Z）-烯胺的立体选择性组装

  摘要：

  公开了在分子氧下芳族伯胺和烯烃的有效Pd催化的氧化偶联。在温和的反应条件下，它可以快速进入具有出色官能团耐受性和出色的区域和立体选择性的（Z）-烯胺化合物。由于其适用于广泛的芳族伯胺，因此大多数人以前无法有效地转化为烯胺，因此这种有吸引力的途径具有重要意义。此外，该协议是可扩展的，并且所得到的烯胺可以方便地转化为一系列含N的杂环，从而说明了其在合成和药物化学中的潜在应用。

  DOI：

  10.1021/jo402117r

文献信息

• Synthesis and <i>in Vitro</i> Testing of Antimalarial Activity of Non-natural-Type Neocryptolepines: Structure–Activity Relationship Study of 2,11- and 9,11-Disubstituted 6-Methylindolo[2,3-<i>b</i>]quinolines
  作者：Ning Wang、Kathryn Jean Wicht、Li Wang、Wen-Jie Lu、Ryuhei Misumi、Ming-qi Wang、Ahmed Abdel Aleem El Gokha、Marcel Kaiser、Ibrahim El Tantawy El Sayed、Timothy John Egan、Tsutomu Inokuchi

  DOI：10.1248/cpb.c13-00639

  日期：——

  This report describes the synthesis and in vitro anti-malarial evaluations of certain C2 or C8 and C11-disubstituted 6-methyl-5H-indolo[2,3-b]quinoline (neocryptolepine congener) derivatives. To attain higher activities, the structure–activity relationship (SAR) studies were conducted by varying the kind of alkylamino or ω-aminoalkylamino stubstituents at C11 and with Cl at the C2 position, or CO2Me

  该报告描述了某些C2或C8和C11-二取代的6-甲基-5H-吲哚并[2,3-b]喹啉（新隐油菜籽同源物）衍生物的合成及体外抗疟疾评估。为了获得更高的活性，通过改变C11处的烷基氨基或ω-氨基烷基氨基取代基的种类进行结构-活性关系（SAR）研究，C2处为Cl，C9处为CO2Me。与11-非（烷基氨基）衍生物相比，所测试化合物的抗疟疾活性显着提高。C11处的3-氨丙基氨基进一步被修饰为尿素和硫脲，从而改善了对正常细胞的细胞毒性。用化合物8和9d对抗NF54菌株可获得最佳结果，IC（50）/ SI值分别为86 nM / 20和317 nM / 370。此外，测试化合物对β-血红素的抑制作用。发现十二个具有低于100 µM的IC（50）值，并且发现那些具有碱性氨基侧链的衍生物在NF54菌株中抑制了β-血红素抑制和细胞生长之间的线性相关性。在NF54活性和与溶剂化和极性有关的理化因素之间鉴定出第二种相关性。
• Synthesis and antimalarial testing of neocryptolepine analogues: Addition of ester function in SAR study of 2,11-disubstituted indolo[2,3-b]quinolines
  作者：Wen-Jie Lu、Kathryn J. Wicht、Li Wang、Kento Imai、Zhen-Wu Mei、Marcel Kaiser、Ibrahim El Tantawy El Sayed、Timothy J. Egan、Tsutomu Inokuchi

  DOI：10.1016/j.ejmech.2013.03.072

  日期：2013.6

  This report describes the synthesis, and in vitro and in vivo antimalarial evaluations of certain ester-modified neocryptolepine (5-methyl-5H-indolo[2,3-b]quinoline) derivatives. The modifications were carried out by introducing ester groups at the C2 and/or C9 position on the neocryptolepine core and the terminal amino group of the 3-aminopropylamine substituents at the C11 position with a urea/thiourea unit. The antiplasmodial activities of our derivative agents against two different strains (CQS: NF54, and CQR: R1) and the cytotoxic activity against normal L6 cells were evaluated. The test results showed that the ester modified neocryptolepine derivatives have higher antiplasmodial activities against both strains and a low cytotoxic activity against normal cells. The best results were achieved by compounds 9c and 12b against the NF54 strain with the IC50/SI value as 2.27 nM/361 and 1.81 nM/321, respectively. While against R1 strain, all the tested compounds showed higher activity than the well-known antimalarial drug chloroquine. Furthermore, the compounds were tested for beta-haematin inhibition and 12 were found to be more active than chloroquine (IC50 = 18 mu M). Structure activity relationship studies exposed an interesting linear correlation between polar surface area of the molecule and beta-haematin inhibition for this series. In vivo testing of compounds 7 and 8a against NF54 strain on Plasmodium berghei female mice showed that the introduction of the ester group increased the antiplasmodial activity of the neocryptolepine core substantially. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Design and Synthesis of 1-Indol-1-yl-propan-2-ones as Inhibitors of Human Cytosolic Phospholipase A₂α
  作者：Joachim Ludwig、Stefanie Bovens、Carsten Brauch、Alwine Schulze Elfringhoff、Matthias Lehr

  DOI：10.1021/jm051243a

  日期：2006.4.1

  The synthesis and structure-activity relationship study of a series of 1-indol-1-yl-3-phenoxypropan-2-one inhibitors of cytosolic phospholipase A(2)alpha (cPLA(2)alpha) are described. The compounds were evaluated in a vesicle assay with isolated cPLA(2)alpha and in cellular assays with intact human platelets. Systematic variation led to 3-methylhydrogen 1-[3-(4-decyloxyphenoxy)-2-oxopropyl]indole-3,5-dicarboxylate (57), which revealed the highest activity against the isolated enzyme. With an IC50 value of 4.3 nM in this assay, it is one of the most potent in vitro cPLA(2)alpha inhibitors known today.
• PANNEXIN-1 MODULATORS AND METHODS OF TREATING DISORDERS IN WHICH PANNEXIN-1 IS IMPLICATED
  申请人：[en]PANNEX THERAPEUTICS INC.

  公开号：WO2024049929A2

  公开（公告）日：2024-03-07

  Disclosed herein are small molecule modulators of pannexin. Also disclosed herein are methods of treating disorders associated with exacerbated activation of ATP- induced signal pathways mediated by pannexin, such as pain and opioid addiction, by administering small molecule modulators of pannexin.
• Palladium-Catalyzed Oxidative Coupling of Aromatic Primary Amines and Alkenes under Molecular Oxygen: Stereoselective Assembly of (<i>Z</i>)-Enamines
  作者：Xiaochen Ji、Huawen Huang、Wanqing Wu、Xianwei Li、Huanfeng Jiang

  DOI：10.1021/jo402117r

  日期：2013.11.15

  An efficient Pd-catalyzed oxidative coupling of aromatic primary amines and alkenes under molecular oxygen is disclosed. Under mild reaction conditions, it provides a rapid access to (Z)-enamine compounds with exceptional functional group tolerance and excellent regio- and stereoselectivity. This attractive route is of great significance due to its applicability to a wide range of aromatic primary

  公开了在分子氧下芳族伯胺和烯烃的有效Pd催化的氧化偶联。在温和的反应条件下，它可以快速进入具有出色官能团耐受性和出色的区域和立体选择性的（Z）-烯胺化合物。由于其适用于广泛的芳族伯胺，因此大多数人以前无法有效地转化为烯胺，因此这种有吸引力的途径具有重要意义。此外，该协议是可扩展的，并且所得到的烯胺可以方便地转化为一系列含N的杂环，从而说明了其在合成和药物化学中的潜在应用。