10-(4′-N-piperidinobutyl)acridone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 10-(4′-N-piperidinobutyl)acridone
• 英文别名: 10-(4-Piperidin-1-ylbutyl)acridin-9-one
• 化学式: C₂₂H₂₆N₂O
• 分子量: 334.461
• InChiKey: GSKUCDVVVYUWKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-苯基邻氨基苯甲酸 在 氢氧化钾 、 PPA 、 四丁基溴化铵 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 3.0h， 生成 10-(4′-N-piperidinobutyl)acridone
  参考文献：
  名称：

  Anti-calmodulin acridone derivatives modulate vinblastine resistance in multidrug resistant (MDR) cancer cells

  摘要：

  Multidrug resistance (MDR) is one of the main obstacles limiting the efficacy of chemotherapy treatment of tumors. Parent acridones 1A and 1B were prepared by the Ullmann reaction followed by cyclization and N-alkylation. N-(omega-Chloroalkyl) analogues were subjected to iodide catalyzed nucleophilic Substitution reaction with secondary amines to get the compounds 3A-13A and 3B-13B, which enhanced the uptake of vinblastine in KBCh(R)-8-5 cells to a greater extent (2.6-13.1-fold relative to control) than verapamil. The study oil the structure-activity relationship revealed that substitution of -H at position C-4 in acridone nucleus by -OCH3 increased the cytotoxic and anti-MDR activities. The ability of acridones to inhibit calmodulin dependent cyclic AMP phosphodiesterase has been determined and the results have shown a strong positive correlation between anti-calmodulin activity and cytotoxicity in KBCh(R)-8-5 cells or anti-MDR activity. (C) 2003 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2003.12.001

文献信息

• Synthesis, cytotoxicity evaluation, and molecular modeling studies of 2,<i>N</i>¹⁰-substituted acridones as DNA-intercalating agents
  作者：Nisachon Khunnawutmanotham、Watthanachai Jumpathong、Chatchakorn Eurtivong、Nitirat Chimnoi、Supanna Techasakul

  DOI：10.1177/1747519820902674

  日期：2020.7

  Acridine-based compounds possess anticancer activities by intercalating to DNA. Although they have chemotherapeutic potential, acridine-based compounds are not used to treat cancer. In this study, 2,N10-acridone derivatives are designed and synthesized based on acridone, a ketone derivative of acridine. Herein, acridone is functionalized with alkyl side chains containing terminal nitrogen-based moieties

  吖啶类化合物通过嵌入 DNA 具有抗癌活性。尽管它们具有化学治疗潜力，但基于吖啶的化合物不用于治疗癌症。本研究以吖啶酮衍生物吖啶酮为基础，设计合成了2,N10-吖啶酮衍生物。在本文中，吖啶酮被烷基侧链官能化，该侧链在 N10 位含有末端氮基部分并在 C2 位被取代。评估产品对四种癌细胞系的体外细胞毒性：Molt-3、HepG2、A549 和 HuCCA-1。在 C2 和 N10 位带有两个丁基哌啶侧链的衍生物是最活跃的，IC50 值范围为 2.96 到 9.46 µM。分子建模研究支持衍生物通过嵌入与 DNA 结合，
• Anti-calmodulin acridone derivatives modulate vinblastine resistance in multidrug resistant (MDR) cancer cells
  作者：Ravi Hegde、Padma Thimmaiah、Mayur C Yerigeri、Gowdahalli Krishnegowda、Kuntebommanahalli N Thimmaiah、Peter J Houghton

  DOI：10.1016/j.ejmech.2003.12.001

  日期：2004.2

  Multidrug resistance (MDR) is one of the main obstacles limiting the efficacy of chemotherapy treatment of tumors. Parent acridones 1A and 1B were prepared by the Ullmann reaction followed by cyclization and N-alkylation. N-(omega-Chloroalkyl) analogues were subjected to iodide catalyzed nucleophilic Substitution reaction with secondary amines to get the compounds 3A-13A and 3B-13B, which enhanced the uptake of vinblastine in KBCh(R)-8-5 cells to a greater extent (2.6-13.1-fold relative to control) than verapamil. The study oil the structure-activity relationship revealed that substitution of -H at position C-4 in acridone nucleus by -OCH3 increased the cytotoxic and anti-MDR activities. The ability of acridones to inhibit calmodulin dependent cyclic AMP phosphodiesterase has been determined and the results have shown a strong positive correlation between anti-calmodulin activity and cytotoxicity in KBCh(R)-8-5 cells or anti-MDR activity. (C) 2003 Elsevier SAS. All rights reserved.