9-(4-hydroxy-3-methoxyphenyl)-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione | 138744-08-8

• 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: 9-(4-hydroxy-3-methoxyphenyl)-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione
• 英文别名: 9-(4-Hydroxy-3-methoxyphenyl)-2,3,4,5,6,7,9,10-octahydroacridine-1,8-dione
• CAS: 138744-08-8
• 化学式: C₂₀H₂₁NO₄
• 分子量: 339.391
• InChiKey: BTZCMKCFTGXQHQ-UHFFFAOYSA-N

物化性质

• 沸点：
  579.5±50.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  对溴甲基苯甲酸 、 9-(4-hydroxy-3-methoxyphenyl)-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione 在 potassium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 4.25h， 以35.6%的产率得到4-((4-(1,8-dioxo-1,2,3,4,5,6,7,8,9,10-decahydroacridin-9-yl)-2-methoxyphenoxy)methyl)benzoic acid
  参考文献：
  名称：

  Discovery of 1,8-acridinedione derivatives as novel GCN5 inhibitors via high throughput screening

  摘要：

  The general control nonrepressed protein 5 (GCN5) plays a crucial role in many biological processes. Dysregulation of GCN5 has been closely related to various human diseases, especially cancers. Hence, the exploitation of small molecules targeting GCN5 is essential for drug design and academic research. Based on the amplified luminescent proximity homogeneous assay screen methodology, we performed high throughput screening and discovered a novel GCN5 inhibitor DC_G16 with 1,8-acridinedione scaffold. Structure optimization led to the identification of a highly potent inhibitor, namely DC_G16-11 with the half-maximal inhibitory concentration (IC50) value of 6.8 mu M. The binding between DC_G16-11 and GCN5 was demonstrated by NMR and SPR with a K-D of 4.2 mu M. It could also inhibit proliferation and induce cell cycle arrest and apoptosis in cancer cells while it presented minimal effects on normal cells. Herein, DC_G16-11 could be applied as a validated chemical probe for GCN5-related biological function research and presented great potential for clinical disease treatment. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.02.005
• 作为产物：
  描述：

  1,3-环己二酮 、 香草醛 在 ammonium acetate 作用下， 以98 %的产率得到9-(4-hydroxy-3-methoxyphenyl)-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione
  参考文献：
  名称：

  新型天然低共熔混合物催化一锅合成1,8-二氧代-十氢吖啶和六氢喹啉衍生物

  摘要：

  在这项工作中，由葡萄糖、普瑞巴林和尿素制备了一种新型天然低共熔混合物，并使用多种技术进行了鉴定，包括傅里叶变换红外光谱、热重分析、导数热重分析、差热分析和折射率测量。表征后，研究了该试剂在一锅Hantzsch缩合合成1,8-二氧代十氢吖啶和六氢喹啉衍生物中的促进能力。所报道的方案最重要的优点包括试剂制备简便、过程绿色、后处理程序简单、产率高和反应时间短。在这项研究中，还研究了所制备的低共熔混合物和一些制备的产品对细菌的抗菌活性。通过琼脂井扩散法检测枯草芽孢杆菌（革兰氏阳性）和大肠杆菌（革兰氏阴性）。

  DOI：

  10.1007/s11164-023-05125-0

文献信息

• 1,4-Dihydropyridine charge control agents for electrostatographic toners and developers
  申请人：EASTMAN KODAK COMPANY

  公开号：EP1109070A2

  公开（公告）日：2001-06-20

  A charge control agent is disclosed selected from the group consisting of 1,4-dihydropyridines having the following general structure: where R1, R2, R3, R4, R5, X, and Z are defined in the specification. These compounds are useful in electrostatographic toners and developers.

  本发明公开了一种电荷控制剂，它选自具有以下一般结构的 1,4-二氢吡啶类： 其中 R1、R2、R3、R4、R5、X 和 Z 的定义见说明书。这些化合物适用于电致发光调色剂和显影剂。
• Jain, S M; Khajuria, R K; Dhar, K L, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1991, vol. 30, # 11, p. 1037 - 1040
  作者：Jain, S M、Khajuria, R K、Dhar, K L、Singh, Surjeet、Bani, S、et al.

  DOI：——

  日期：——
• US6265127B1
  申请人：——

  公开号：US6265127B1

  公开（公告）日：2001-07-24
• Discovery of 1,8-acridinedione derivatives as novel GCN5 inhibitors via high throughput screening
  作者：Huan Xiong、Jie Han、Jun Wang、Wenchao Lu、Chen Wang、Yu Chen、Fulin Lian、Naixia Zhang、Yu-Chih Liu、Chenhua Zhang、Hong Ding、Hualiang Jiang、Wencong Lu、Cheng Luo、Bing Zhou

  DOI：10.1016/j.ejmech.2018.02.005

  日期：2018.5

  The general control nonrepressed protein 5 (GCN5) plays a crucial role in many biological processes. Dysregulation of GCN5 has been closely related to various human diseases, especially cancers. Hence, the exploitation of small molecules targeting GCN5 is essential for drug design and academic research. Based on the amplified luminescent proximity homogeneous assay screen methodology, we performed high throughput screening and discovered a novel GCN5 inhibitor DC_G16 with 1,8-acridinedione scaffold. Structure optimization led to the identification of a highly potent inhibitor, namely DC_G16-11 with the half-maximal inhibitory concentration (IC50) value of 6.8 mu M. The binding between DC_G16-11 and GCN5 was demonstrated by NMR and SPR with a K-D of 4.2 mu M. It could also inhibit proliferation and induce cell cycle arrest and apoptosis in cancer cells while it presented minimal effects on normal cells. Herein, DC_G16-11 could be applied as a validated chemical probe for GCN5-related biological function research and presented great potential for clinical disease treatment. (C) 2018 Elsevier Masson SAS. All rights reserved.