N¹-(acridin-9-yl)-N⁴,N⁴-diethylbenzene-1,4-diamine | 110022-12-3

• 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: N¹-(acridin-9-yl)-N⁴,N⁴-diethylbenzene-1,4-diamine
• 英文别名: N-Acridin-9-yl-N',N'-diethyl-benzene-1,4-diamine；1-N-acridin-9-yl-4-N,4-N-diethylbenzene-1,4-diamine
• CAS: 110022-12-3
• 化学式: C₂₃H₂₃N₃
• 分子量: 341.456
• InChiKey: RSDMAKAJBGXVLZ-UHFFFAOYSA-N

物化性质

• 熔点：
  227-228 °C
• 沸点：
  511.0±35.0 °C(Predicted)
• 密度：
  1.185±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  苯胺 在 盐酸 、 铜 、 potassium carbonate 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 N¹-(acridin-9-yl)-N⁴,N⁴-diethylbenzene-1,4-diamine
  参考文献：
  名称：

  新型吖啶基LSD1抑制剂增强胃癌的免疫反应

  摘要：

  最近，组蛋白赖氨酸特异性去甲基酶 1 (LSD1) 已成为癌症免疫治疗的新兴且有前景的靶点。在此，基于我们之前报道的LSD1抑制剂DXJ-1（也称为6x），通过结构优化鉴定了一系列新型吖啶基LSD1抑制剂。其中，化合物5ac对LSD1的抑制活性显着增强，IC 50值为13 nM，比DXJ-1（IC 50  = 73 nM）强约4.6倍。分子对接研究表明，化合物5ac可以很好地对接至LSD1的活性位点。进一步的机制研究表明，化合物5ac抑制胃癌细胞的干细胞性和迁移，并降低BGC-823和MFC细胞中PD-L1的表达。更重要的是，当用化合物5ac处理时，BGC-823 细胞对 T 细胞杀伤更加敏感。此外，化合物5ac还可以抑制小鼠体内的肿瘤生长。总之，5ac可以作为增强胃癌免疫反应的有前途的候选者。

  DOI：

  10.1016/j.ejmech.2023.115684

文献信息

• Antiprion activity of functionalized 9-aminoacridines related to quinacrine
  作者：Hanh Thuy Nguyen Thi、Chong-Yew Lee、Kenta Teruya、Wei-Yi Ong、Katsumi Doh-ura、Mei-Lin Go

  DOI：10.1016/j.bmc.2008.05.060

  日期：2008.7

  A library of functionalized 6-chloro-2-methoxy-(N-9-substituted) acridin-9-amines structurally related to quinacrine were synthesized and evaluated for antiprion activity on four different cell models persistently infected with scrapie prion strains (ScN2a, N167, Ch2) or a human disease prion strain (F3). Most of the compounds were distinguished by the side chain attached to 9-amino of the acridine ring. These were dialkylaminoalkyl and phenyl with basic groups on the phenyl ring. The most promising compound was 6-chloro-2-methoxy-N-(4-(4-methylpiperazin-1-yl) phenyl) acridin-9-amine (15) which had submicromolar EC50 values (0.1-0.7 mu M) on all cell models, was able to clear PrPSc at non-toxic concentrations of 1.2-2.5 mu M, and was more active than quinacrine in terms of EC50 values. Other promising compounds were 14 (a regioisomer of 15) and 17 which had a 1-benzylpiperidin-4-yl substituent attached to the 9-amino function. Activity was strongly dependent on the presence of a substituted acridine ring, which in this library comprised 6-chloro-2-methoxy substituents on the acridine ring. The side chains of 14, 15, and 17 have not been previously associated with antiprion activity and are interesting leads for further optimization of antiprion activity. (c) 2008 Elsevier Ltd. All rights reserved.
• Novel acridine-based LSD1 inhibitors enhance immune response in gastric cancer
  作者：Xing-Jie Dai、Ying Liu、Ning Wang、He-Xiang Chen、Jiang-Wan Wu、Xiao-Peng Xiong、Shi-Kun Ji、Ying Zhou、Liang Shen、Shao-Peng Wang、Hong-Min Liu、Hui-Min Liu、Yi-Chao Zheng

  DOI：10.1016/j.ejmech.2023.115684

  日期：2023.11

  lysine specific demethylase 1 (LSD1) has become an emerging and promising target for cancer immunotherapy. Herein, based on our previously reported LSD1 inhibitor DXJ-1 (also called 6x), a series of novel acridine-based LSD1 inhibitors were identified via structure optimizations. Among them, compound 5ac demonstrated significantly enhanced inhibitory activity against LSD1 with an IC50 value of 13 nM,

  最近，组蛋白赖氨酸特异性去甲基酶 1 (LSD1) 已成为癌症免疫治疗的新兴且有前景的靶点。在此，基于我们之前报道的LSD1抑制剂DXJ-1（也称为6x），通过结构优化鉴定了一系列新型吖啶基LSD1抑制剂。其中，化合物5ac对LSD1的抑制活性显着增强，IC 50值为13 nM，比DXJ-1（IC 50  = 73 nM）强约4.6倍。分子对接研究表明，化合物5ac可以很好地对接至LSD1的活性位点。进一步的机制研究表明，化合物5ac抑制胃癌细胞的干细胞性和迁移，并降低BGC-823和MFC细胞中PD-L1的表达。更重要的是，当用化合物5ac处理时，BGC-823 细胞对 T 细胞杀伤更加敏感。此外，化合物5ac还可以抑制小鼠体内的肿瘤生长。总之，5ac可以作为增强胃癌免疫反应的有前途的候选者。