4-(2-(7-methoxy-1H-indol-1-yl)ethyl)morpholine | 1438278-45-5

• 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
• 英文名称: 4-(2-(7-methoxy-1H-indol-1-yl)ethyl)morpholine
• 英文别名: 4-[2-(7-Methoxyindol-1-yl)ethyl]morpholine；4-[2-(7-methoxyindol-1-yl)ethyl]morpholine
• CAS: 1438278-45-5
• 化学式: C₁₅H₂₀N₂O₂
• 分子量: 260.336
• InChiKey: VFOMHNXWLXDGLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  26.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-(7-methoxy-1H-indol-1-yl)ethyl)morpholine 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 N-((3s,5s,7s)-adamantan-1-yl)-7-methoxy-1-(2-morpholinoethyl)-1H-indole-3-carboxamide
  参考文献：
  名称：

  酰胺基烷基吲哚作为有力和选择性的多发性硬化症小鼠模型体内功效的选择性大麻素2型受体激动剂。

  摘要：

  选择性CB 2激动剂代表了一种有吸引力的治疗策略，可用于治疗各种疾病，而无需CB 1受体介导的精神病副作用。我们对黑市设计师药物SDB-001进行了合理的优化，从而确定了有效的和选择性的CB 2激动剂。3-氨基烷基吲哚处的7-甲氧基或7-甲硫基取代产生有效的CB 2拮抗剂（27或28，IC 50 = 16-28 nM）。从吲哚环的3位到2位取代酰胺基烷基大大提高了CB 2上的激动剂选择性，而不是CB 1上受体。特别是，化合物57对CB 2受体表现出有效的激动剂活性（EC 50 = 114–142 nM），而对CB 1受体没有明显的激动剂或拮抗剂活性。此外，在多发性硬化症的实验性自身免疫性脑脊髓炎（EAE）小鼠模型中，有57个显着减轻了临床症状并保护了小鼠中枢神经系统免受免疫损伤。

  DOI：

  10.1021/acs.jmedchem.7b00724
• 作为产物：
  描述：

  2-(4-吗啉)乙基溴 、 7-甲氧基吲哚 在 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以74%的产率得到4-(2-(7-methoxy-1H-indol-1-yl)ethyl)morpholine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Aminoalkylindole Derivatives as Cannabinoid Receptor Ligands with Potential for Treatment of Alcohol Abuse

  摘要：

  Attenuation of increased endocannabinoid signaling with a CB1R neutral antagonist might offer a new therapeutic direction for treatment of alcohol abuse. We have recently reported that a monohydroxylated metabolite of the synthetic aminoalkylindole cannabinoid JHW-073 (3) exhibits neutral antagonist activity at CB1Rs and thus may serve as a promising lead for the development of novel alcohol abuse therapies. In the current study, we show that systematic modification of an aminoalkylindole scaffold identified two new compounds with dual CB1R antagonist/CB2R agonist activity. Similar to the CB1R antagonist/inverse agonist rimonabant, analogues 27 and 30 decrease oral alcohol self-administration without affecting total fluid intake and block the development of alcohol-conditioned place preference. Collectively, these initial findings suggest that design and systematic modification of aminoalkylindoles such as 3 may lead to development of novel cannabinoid ligands with dual CB1R antagonist/CB2R agonist activity with potential for use as treatments of alcohol abuse.

  DOI：

  10.1021/jm400268b

文献信息

• Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis
  作者：Ying Shi、Yan-Hui Duan、Yue-Yang Ji、Zhi-Long Wang、Yan-Ran Wu、Hendra Gunosewoyo、Xiao-Yu Xie、Jian-Zhong Chen、Fan Yang、Jing Li、Jie Tang、Xin Xie、Li-Fang Yu

  DOI：10.1021/acs.jmedchem.7b00724

  日期：2017.8.24

  in potent CB2 antagonists (27 or 28, IC50 = 16–28 nM). Replacement of the amidoalkyls from 3-position to the 2-position of the indole ring dramatically increased the agonist selectivity on the CB2 over CB1 receptor. Particularly, compound 57 displayed a potent agonist activity on the CB2 receptor (EC50 = 114–142 nM) without observable agonist or antagonist activity on the CB1 receptor. Furthermore,

  选择性CB 2激动剂代表了一种有吸引力的治疗策略，可用于治疗各种疾病，而无需CB 1受体介导的精神病副作用。我们对黑市设计师药物SDB-001进行了合理的优化，从而确定了有效的和选择性的CB 2激动剂。3-氨基烷基吲哚处的7-甲氧基或7-甲硫基取代产生有效的CB 2拮抗剂（27或28，IC 50 = 16-28 nM）。从吲哚环的3位到2位取代酰胺基烷基大大提高了CB 2上的激动剂选择性，而不是CB 1上受体。特别是，化合物57对CB 2受体表现出有效的激动剂活性（EC 50 = 114–142 nM），而对CB 1受体没有明显的激动剂或拮抗剂活性。此外，在多发性硬化症的实验性自身免疫性脑脊髓炎（EAE）小鼠模型中，有57个显着减轻了临床症状并保护了小鼠中枢神经系统免受免疫损伤。
• Design, Synthesis, and Biological Evaluation of Aminoalkylindole Derivatives as Cannabinoid Receptor Ligands with Potential for Treatment of Alcohol Abuse
  作者：Tamara Vasiljevik、Lirit N. Franks、Benjamin M. Ford、Justin T. Douglas、Paul L. Prather、William E. Fantegrossi、Thomas E. Prisinzano

  DOI：10.1021/jm400268b

  日期：2013.6.13

  Attenuation of increased endocannabinoid signaling with a CB1R neutral antagonist might offer a new therapeutic direction for treatment of alcohol abuse. We have recently reported that a monohydroxylated metabolite of the synthetic aminoalkylindole cannabinoid JHW-073 (3) exhibits neutral antagonist activity at CB1Rs and thus may serve as a promising lead for the development of novel alcohol abuse therapies. In the current study, we show that systematic modification of an aminoalkylindole scaffold identified two new compounds with dual CB1R antagonist/CB2R agonist activity. Similar to the CB1R antagonist/inverse agonist rimonabant, analogues 27 and 30 decrease oral alcohol self-administration without affecting total fluid intake and block the development of alcohol-conditioned place preference. Collectively, these initial findings suggest that design and systematic modification of aminoalkylindoles such as 3 may lead to development of novel cannabinoid ligands with dual CB1R antagonist/CB2R agonist activity with potential for use as treatments of alcohol abuse.