5-(Nonyloxy)tryptamine hydrochloride | 171783-23-6

• 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: 5-(Nonyloxy)tryptamine hydrochloride
• 英文别名: Kxj9KD9awl；2-(5-nonoxy-1H-indol-3-yl)ethanamine;hydrochloride
• CAS: 171783-23-6
• 化学式: C₁₉H₃₀N₂O*ClH
• 分子量: 338.921
• InChiKey: WVSBVULKJPWRBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.22
• 重原子数：
  23
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  51
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(Nonyloxy)tryptamine hydrochloride 、 碘甲烷 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 trimethyl-[2-(5-nonoxy-1H-indol-3-yl)ethyl]azanium
  参考文献：
  名称：

  5-Alkyloxytryptamines are membrane-targeting, broad-spectrum antibiotics

  摘要：

  Antibiotic adjuvant therapy represents an exciting opportunity to enhance the activity of clinical antibiotics by co-dosing with a secondary small molecule. Successful adjuvants decrease the concentration of antibiotics used to defeat bacteria, increase activity (in some cases introducing activity against organisms that are drug resistant), and reduce the frequency at which drug-resistant bacteria emerge. We report that 5-alkyloxytryptamines are a new class of broad-spectrum antibacterial agents with exciting activity as antibiotic adjuvants. We synthesized 5-alkyloxytryptamine analogs and found that an alkyl chain length of 6-12 carbons and a primary ammonium group are necessary for the antibacterial activity of the compounds, and an alkyl chain length of 6-10 carbons increased the membrane permeability of Gram-positive and Gram-negative bacteria. Although several of the most potent analogs also have activity against the membranes of human embryonic kidney cells, we demonstrate that below the minimum inhibitory concentration (MIC) where mammalian cell toxicity is low these compounds may be successfully used as adjuvants for chloramphenicol, tetracycline, ciprofloxacin, and rifampicin against clinical strains of Salmonella typhimurium, Acinetobacter baumannii and Staphylococcus aureus, reducing MIC values by as much as several logs. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.10.004
• 作为产物：
  描述：

  1-溴壬烷 在 盐酸 、 potassium carbonate 作用下， 以 乙酸乙酯 、 乙腈 为溶剂， 反应 26.0h， 生成 5-(Nonyloxy)tryptamine hydrochloride
  参考文献：
  名称：

  血清素的O-烷基衍生物在人5-HT1Dβ受体上的结合。

  摘要：

  在人类中，5-HT1D血清素受体代表末端自身受体，并且有一些证据表明5-HT1D配体可用于治疗偏头痛。最广泛使用的5-HT1D激动剂是舒马普坦。然而，据报道该试剂对5-HT1D的选择性相对于5-HT1A受体几乎没有。为了鉴定具有增强的5-HT1D相对于5-HT1A选择性的新型5-羟色胺能药物，我们尝试利用与这两个受体的5-HT结合位点的5-位相关的体积耐受性区域中的可能差异。对一系列5-（烷氧基）色胺的衍生物的研究表明，具有多达8个碳原子的直链烷基的化合物以高亲和力与人5-HT1Dβ受体结合（Ki < 5 nM），但相对于5-HT1A受体，选择性不足50倍。长于八个碳原子的烷基会降低对5-HT1A受体的亲和力，而长于九个碳原子的烷基会导致对5-HT1Dβ受体的亲和力降低的化合物。5-（壬氧基）色胺（10）代表具有最佳5-HT1Dβ亲和力（Ki = 1 nM）和选择性（> 300倍）的化合物。烷基链分支成5-[（（7

  DOI：

  10.1021/jm950498t

文献信息

• Serotonin Analogues as Inhibitors of Breast Cancer Cell Growth
  作者：Jiney Jose、Clint D. J. Tavares、Nancy D. Ebelt、Alessia Lodi、Ramakrishna Edupuganti、Xuemei Xie、Ashwini K. Devkota、Tamer S. Kaoud、Carla L. Van Den Berg、Eric V. Anslyn、Stefano Tiziani、Chandra Bartholomeusz、Kevin N. Dalby

  DOI：10.1021/acsmedchemlett.7b00282

  日期：2017.10.12

  cancer cell lines. Thus, we synthesized a series of novel alkyloxytryptamine analogues, several of which decreased the viability of various human cancer cell lines. Proteomic and metabolomic analyses showed that compounds 6 and 10 induced apoptosis and interfered with signaling pathways that regulate protein translation and survival, such as the Akt/mTOR pathway, in triple-negative breast cancer cells

  5-羟色胺（5-羟色胺，5-HT）是乳腺上皮稳态的关键局部调节剂，可通过多种受体发挥作用。据报道，5-羟色胺信号转导的失调通过增强细胞增殖并增强对凋亡的抵抗力而有助于乳腺癌的病理生理。初步分析表明，强效的5-HT1B / 1D血清素受体激动剂5-壬基氧基色胺（5-NT）（一种曲普坦样分子）可诱导乳腺癌细胞系中的细胞死亡。因此，我们合成了一系列新颖的烷氧基色胺类似物，其中一些降低了各种人类癌细胞系的生存能力。蛋白质组学和代谢组学分析表明化合物6和10 在三阴性乳腺癌细胞中诱导凋亡，并干扰调节蛋白质翻译和存活的信号传导途径，例如Akt / mTOR途径。
• Molecular adjuvants for enhanced cytosolic delivery of active agents
  申请人：Universiteit Gent

  公开号：US11033572B2

  公开（公告）日：2021-06-15

  The present invention relates to a method and compositions for optimized intracellular delivery of active agents, in particular nucleic acids, using a specific class of adjuvants. The method and compositions of the invention enhance cytosolic release of the agents and can be used for the treatment of various disorders.

  本发明涉及一种使用特定类别佐剂优化活性剂（尤其是核酸）细胞内递送的方法和组合物。本发明的方法和组合物能增强药剂的细胞释放，可用于治疗各种疾病。
• MOLECULAR ADJUVANTS FOR ENHANCED CYTOSOLIC DELIVERY OF ACTIVE AGENTS
  申请人：Universiteit Gent

  公开号：US20190328768A1

  公开（公告）日：2019-10-31

  The present invention relates to a method and compositions for optimized intracellular delivery of active agents, in particular nucleic acids, using a specific class of adjuvants. The method and compositions of the invention enhance cytosolic release of the agents and can be used for the treatment of various disorders.
• Binding of <i>O</i>-Alkyl Derivatives of Serotonin at Human 5-HT1Dβ Receptors
  作者：Richard A. Glennon、Seoung-Soo Hong、Mikhail Bondarev、Ho Law、Malgorzata Dukat、Suman Rakhit、Patricia Power、Ermei Fan、Diana Kinneau、Rajender Kamboj、Milt Teitler、Katharine Herrick-Davis、Carol Smith

  DOI：10.1021/jm950498t

  日期：1996.1.1

  populations of receptors. Examination of a series of 5-(alkyloxy)tryptamine derivatives demonstrated that compounds with unbranched alkyl groups of up to eight carbon atoms bind with high affinity at human 5-HT1D beta receptors (Ki < 5 nM) but demonstrate less than 50-fold selectivity relative to 5-HT1A receptors. Alkyl groups longer than eight carbon atoms impart reduced affinity for 5-HT1A receptors whereas

  在人类中，5-HT1D血清素受体代表末端自身受体，并且有一些证据表明5-HT1D配体可用于治疗偏头痛。最广泛使用的5-HT1D激动剂是舒马普坦。然而，据报道该试剂对5-HT1D的选择性相对于5-HT1A受体几乎没有。为了鉴定具有增强的5-HT1D相对于5-HT1A选择性的新型5-羟色胺能药物，我们尝试利用与这两个受体的5-HT结合位点的5-位相关的体积耐受性区域中的可能差异。对一系列5-（烷氧基）色胺的衍生物的研究表明，具有多达8个碳原子的直链烷基的化合物以高亲和力与人5-HT1Dβ受体结合（Ki < 5 nM），但相对于5-HT1A受体，选择性不足50倍。长于八个碳原子的烷基会降低对5-HT1A受体的亲和力，而长于九个碳原子的烷基会导致对5-HT1Dβ受体的亲和力降低的化合物。5-（壬氧基）色胺（10）代表具有最佳5-HT1Dβ亲和力（Ki = 1 nM）和选择性（> 300倍）的化合物。烷基链分支成5-[（（7
• 5-Alkyloxytryptamines are membrane-targeting, broad-spectrum antibiotics
  作者：Katherine C. Faulkner、Katherine A. Hurley、Douglas B. Weibel

  DOI：10.1016/j.bmcl.2016.10.004

  日期：2016.11

  Antibiotic adjuvant therapy represents an exciting opportunity to enhance the activity of clinical antibiotics by co-dosing with a secondary small molecule. Successful adjuvants decrease the concentration of antibiotics used to defeat bacteria, increase activity (in some cases introducing activity against organisms that are drug resistant), and reduce the frequency at which drug-resistant bacteria emerge. We report that 5-alkyloxytryptamines are a new class of broad-spectrum antibacterial agents with exciting activity as antibiotic adjuvants. We synthesized 5-alkyloxytryptamine analogs and found that an alkyl chain length of 6-12 carbons and a primary ammonium group are necessary for the antibacterial activity of the compounds, and an alkyl chain length of 6-10 carbons increased the membrane permeability of Gram-positive and Gram-negative bacteria. Although several of the most potent analogs also have activity against the membranes of human embryonic kidney cells, we demonstrate that below the minimum inhibitory concentration (MIC) where mammalian cell toxicity is low these compounds may be successfully used as adjuvants for chloramphenicol, tetracycline, ciprofloxacin, and rifampicin against clinical strains of Salmonella typhimurium, Acinetobacter baumannii and Staphylococcus aureus, reducing MIC values by as much as several logs. (C) 2016 Elsevier Ltd. All rights reserved.