N-ethyl-N-((5-fluoro-1-octyl-1H-indol-3-yl)methyl)ethanamine | 1244769-48-9

• 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: N-ethyl-N-((5-fluoro-1-octyl-1H-indol-3-yl)methyl)ethanamine
• 英文别名: N-ethyl-N-[(5-fluoro-1-octylindol-3-yl)methyl]ethanamine
• CAS: 1244769-48-9
• 化学式: C₂₁H₃₃FN₂
• 分子量: 332.505
• InChiKey: SSNMQSSXTMNMQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  8.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-溴辛烷 在 sodium hydride 、 溶剂黄146 作用下， 以 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 24.0h， 生成 N-ethyl-N-((5-fluoro-1-octyl-1H-indol-3-yl)methyl)ethanamine
  参考文献：
  名称：

  Amphiphilic Indole Derivatives as Antimycobacterial Agents: Structure–Activity Relationships and Membrane Targeting Properties

  摘要：

  Antibacterials that disrupt cell membrane function have the potential to eradicate "persister" organisms and delay the emergence of resistance. Here we report the antimycobacterial activities of 4-fluoro and 6-methoxyindoles bearing a cationic amphiphilic motif represented by a lipophilic n-octyl side chain at position 1 and a positively charged azepanyl or 1,4-dioxa-8-azaspiro[4.5]decane moiety at position 3. These analogues exhibited balanced profiles of potency (Mycobacterium bovis BCG, M tuberculosis H37Rv), selective activity, solubility, and metabolic stability. Bacteriological mechanism of action investigations on a representative analogue revealed cell membrane permeabilization and depolarization in M bovis BCG. These membrane-related changes preceded cell death indicating that the loss in membrane integrity was not an epiphenomenon. Bactericidal activity was observed against both growing and nongrowing mycobacterial cultures. The analogue also upregulated cell envelope stress inducible promoters piniBAC and pclgR, implicating the involvement of envelope-related targets in its mode of action.

  DOI：

  10.1021/acs.jmedchem.6b01530

文献信息

• Amino Derivatives of Indole As Potent Inhibitors of Isoprenylcysteine Carboxyl Methyltransferase
  作者：Mei-Lin Go、Jo Lene Leow、Suresh Kumar Gorla、Andreas Peter Schüller、Mei Wang、Patrick J. Casey

  DOI：10.1021/jm1002843

  日期：2010.10.14

  The enzyme isoprenylcysteine carboxyl methyltransferase (Icmt) plays an important role in the post-translational modification of proteins that are involved in the regulation of cell growth. The indole acetamide cysmethynil is by far the most potent and widely investigated Icmt inhibitor, but it has modest antiproliferative activity and may have pharmacokinetic limitations due to its lipophilic character

  异戊烯基半胱氨酸羧基甲基转移酶（Icmt）在参与细胞生长调节的蛋白质的翻译后修饰中起着重要作用。吲哚乙酰胺氰菊酯是迄今为止最有效和研究最广泛的Icmt抑制剂，但它具有适度的抗增殖活性，并且由于其亲脂性而可能具有药代动力学限制。我们在这里报告说，可以将cysmethynil进行结构修饰，以产生与抑制Icmt一样有效但具有显着更大的抗增殖活性的类似物。关键的修饰是用叔氨基取代乙酰胺侧链，用异戊二烯基取代正辛基侧链，然后用5- m-甲苯基环被氟取代。而且，这些类似物具有较低的亲脂性，这可以导致改善的药代动力学特征。
• Functionalized indoleamines as potent, drug-like inhibitors of isoprenylcysteine carboxyl methyltransferase (Icmt)
  作者：Pondy M. Ramanujulu、Tianming Yang、Siew-Qi Yap、Fui-Chung Wong、Patrick J. Casey、Mei Wang、Mei-Lin Go

  DOI：10.1016/j.ejmech.2013.02.007

  日期：2013.5

  The enzyme isoprenylcysteine carboxyl methyltransferase (Icmt) plays an important role in the post-translational modification of proteins involved in the regulation of cell growth and oncogenesis. The biological consequences of Icmt inhibition strongly implicate the enzyme as a potential therapeutic target for cancer and provide a compelling rationale for developing specific Icmt inhibitors as anti-cancer

  异戊烯基半胱氨酸羧基甲基转移酶（Icmt）在蛋白质的翻译后修饰中起重要作用，该蛋白质参与调节细胞的生长和致癌作用。Icmt抑制的生物学结果强烈暗示了该酶可能成为癌症的潜在治疗靶标，并为开发特定的Icmt抑制剂作为抗癌剂提供了令人信服的理由。我们在这里报告了已知的Icmt抑制剂cysmethynil的系统修饰，以产生类似物15大大提高了溶解度和PAMPA渗透性，同时获得了Icmt抑制和基于细胞的抗增殖活性。修改涉及叔胺取代cysmethynil的酰胺侧链，并引入代替氨基嘧啶环米甲苯基。弱碱性和极性氨基嘧啶环的存在对最终化合物的效价和类药物特性有显着贡献。
• SMALL MOLECULE INHIBITORS OF ISOPRENYLCYSTEINE CARBOXYL METHYLTRANSFERASE WITH POTENTIAL ANTICANCER ACTIVITY
  申请人：Leow Jo Lene

  公开号：US20120197014A1

  公开（公告）日：2012-08-02

  The present invention generally relates to inhibitors of isoprenylcysteine carboxyl methyltransferase (Icmt), in particularly to compounds that inhibit Icmt activity and pharmaceutical compositions thereof. The invention also relates to methods of disease treatment using the same.

  本发明通常涉及异戊二烯基半胱氨酸羧甲基转移酶（Icmt）的抑制剂，特别是抑制Icmt活性的化合物及其药物组合物。本发明还涉及使用这些抑制剂进行疾病治疗的方法。
• US8742100B2
  申请人：——

  公开号：US8742100B2

  公开（公告）日：2014-06-03
• Amphiphilic Indole Derivatives as Antimycobacterial Agents: Structure–Activity Relationships and Membrane Targeting Properties
  作者：Tianming Yang、Wilfried Moreira、Samuel Agyei Nyantakyi、Huan Chen、Dinah binte Aziz、Mei-Lin Go、Thomas Dick

  DOI：10.1021/acs.jmedchem.6b01530

  日期：2017.4.13

  Antibacterials that disrupt cell membrane function have the potential to eradicate "persister" organisms and delay the emergence of resistance. Here we report the antimycobacterial activities of 4-fluoro and 6-methoxyindoles bearing a cationic amphiphilic motif represented by a lipophilic n-octyl side chain at position 1 and a positively charged azepanyl or 1,4-dioxa-8-azaspiro[4.5]decane moiety at position 3. These analogues exhibited balanced profiles of potency (Mycobacterium bovis BCG, M tuberculosis H37Rv), selective activity, solubility, and metabolic stability. Bacteriological mechanism of action investigations on a representative analogue revealed cell membrane permeabilization and depolarization in M bovis BCG. These membrane-related changes preceded cell death indicating that the loss in membrane integrity was not an epiphenomenon. Bactericidal activity was observed against both growing and nongrowing mycobacterial cultures. The analogue also upregulated cell envelope stress inducible promoters piniBAC and pclgR, implicating the involvement of envelope-related targets in its mode of action.