3-((9H-carbazol-4-yl)oxy)-N-(2-(2-methoxyphenoxy)ethyl)propan-1-amine

• 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: 3-((9H-carbazol-4-yl)oxy)-N-(2-(2-methoxyphenoxy)ethyl)propan-1-amine
• 英文别名: 3-(9H-carbazol-4-yloxy)-N-[2-(2-methoxyphenoxy)ethyl]propan-1-amine
• 化学式: C₂₄H₂₆N₂O₃
• 分子量: 390.482
• InChiKey: ZIIMCNZAFNETMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  55.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-羟基咔唑 在 potassium carbonate 、 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 16.0h， 生成 3-((9H-carbazol-4-yl)oxy)-N-(2-(2-methoxyphenoxy)ethyl)propan-1-amine
  参考文献：
  名称：

  新系列卡维地洛衍生物的设计、合成和生物学评估，通过阻断机械电传感器通道保护感觉毛细胞免受氨基糖苷类诱导的损伤。

  摘要：

  氨基糖苷类 (AG) 是用于治疗严重细菌感染的广谱抗生素，但具有限制使用的副作用，包括不可逆的听力损失。在这里，我们评估了卡维地洛在小鼠耳蜗培养和体内斑马鱼试验中的耳保护特性，并研究了它的保护机制，我们发现这可能是由毛细胞的机电传感器 (MET) 通道（主要进入途径）的阻断介导的对于 AG。为了了解卡维地洛的全部耳部保护潜力，制备了一系列 18 种类似物，并评估了它们对 AG 引起的损伤的作用以及它们对 MET 通道的亲和力。发现一种衍生物在耳蜗培养中比卡维地洛本身具有更大的保护作用，并且与 MET 通道的结合更紧密。

  DOI：

  10.1021/acs.jmedchem.8b01325

文献信息

• Pharmaceutical compositions comprising perillyl alcohol derivatives
  申请人：NeOnc Technologies, Inc.

  公开号：US10696680B2

  公开（公告）日：2020-06-30

  A pharmaceutical composition is provided which includes perillyl alcohol conjugated with a therapeutic agent and further includes and a hydrolyzable acylated aliphatic tail. A method of using the pharmaceutical composition is also provided for treating a condition or disease of a patient, e.g., cancer.

  本发明提供了一种药物组合物，其中包括与治疗剂共轭的紫苏醇，还包括可水解的酰化脂肪族尾部。还提供了一种使用该药物组合物的方法，用于治疗患者的病症或疾病，如癌症。
• Pharmaceutical compositions comprising POH derivatives
  申请人：NeOnc Technologies, Inc.

  公开号：US11013804B2

  公开（公告）日：2021-05-25

  The present invention provides for a perillyl alcohol (POH) carbamate, such as POH-Rolipram. The present invention also provides for a method of treating a disease such as cancer, by delivering to a patient a therapeutically effective amount of POH-Rolipram.

  本发明提供了一种紫苏醇（POH）氨基甲酸酯，如 POH-Rolipram。本发明还提供了一种通过向患者提供治疗有效量的 POH-Rolipram 来治疗癌症等疾病的方法。
• Drug repurposing and rediscovery: Design, synthesis and preliminary biological evaluation of 1-arylamino-3-aryloxypropan-2-ols as anti-melanoma agents
  作者：Qi Chang、Jing Long、Liqing Hu、Zhuo Chen、Qianbin Li、Gaoyun Hu

  DOI：10.1016/j.bmc.2020.115404

  日期：2020.5

  Malignant melanoma (MM) presents as the highest morbidity and mortality type in skin cancer. Herein, inspired by the previously reported anti-melanoma effect of propranolol, a widely applied beta adrenergic receptor antagonist as cardiovascular drug, we set out to exploit its potential as anti-melanoma therapy based on the drug repurposing strategy. Structural optimization of propranolol yielded 5m, which exhibits dramatically improved potency on human melanoma cell growth (1.98-3.70 mu M), compared to propranolol (59.5-75.8 mu M). Further investigation demonstrated that 5m could inhibit colony formation of melanoma cell line (completely abolished at 2 mu M for 5m, partially inhibited at 50 mu M for propranolol), induce cell apoptosis and cell cycle arrest in the G(2)/M phase (both observed at 1 mu M). Preliminary mechanism study indicated that 5m could disrupt the cellular microtubule network, which suggested tubulin as a potential target. Docking study provided a structural insight into the interaction between 5m and tubulin. In summary, our study presents a drug repurposing case that redirects a cardiovascular agent to an anti-melanoma agent.
• Hybridization of β-Adrenergic Agonists and Antagonists Confers G Protein Bias
  作者：Markus Stanek、Louis-Philippe Picard、Maximilian F. Schmidt、Jonas M. Kaindl、Harald Hübner、Michel Bouvier、Dorothée Weikert、Peter Gmeiner

  DOI：10.1021/acs.jmedchem.9b00349

  日期：2019.5.23

  Starting from the beta-adrenoceptor agonist isoprenaline and beta-blocker carvedilol, we designed and synthesized three different chemotypes of agonist/antagonist hybrids. Investigations of ligand-mediated receptor activation using bioluminescence resonance energy transfer biosensors revealed a predominant effect of the aromatic head group on the intrinsic activity of our ligands, as ligands with a carvedilol head group were devoid of agonistic activity. Ligands composed of a catechol head group and an antagonist-like oxypropylene spacer possess significant intrinsic activity for the activation of Gas, while they only show weak or even no beta-arrestin-2 recruitment at both beta(1)- and beta(2)-AR Molecular dynamics simulations suggest that the difference in G protein efficacy and beta-arrestin recruitment of the hybrid (S)-22, the full agonist epinephrine, and the beta(2)-selective, G protein-biased partial agonist salmeterol depends on specific hydrogen bonding between Ser(5.46) and Asn(6.55), and the aromatic head group of the ligands.
• CONTROLLED RELEASE PHARMACEUTICAL COMPOSITION CONTAINING CARVEDILOL
  申请人：Egis Gyógyszergyár Nyilvánosan Múködö Részvénytársaság

  公开号：EP1928431B1

  公开（公告）日：2008-12-31