N,N-diethyl-N'-(6-chloro-2-methoxy-acridin-9-yl)-p-phenylenediamine

• 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: N,N-diethyl-N'-(6-chloro-2-methoxy-acridin-9-yl)-p-phenylenediamine
• 英文别名: N,N-Diaethyl-N'-(6-chlor-2-methoxy-acridin-9-yl)-p-phenylendiamin；6-Chloro-9-(p-diethylaminoanilino)-2-methoxyacridine；1-N-(6-chloro-2-methoxyacridin-9-yl)-4-N,4-N-diethylbenzene-1,4-diamine
• 化学式: C₂₄H₂₄ClN₃O
• 分子量: 405.927
• InChiKey: LQHFYOHONIWKND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  37.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6,9-二氯-2-甲氧基吖啶 、 N,N-二乙基对苯二胺 在 苯酚 作用下， 反应 1.0h， 生成 N,N-diethyl-N'-(6-chloro-2-methoxy-acridin-9-yl)-p-phenylenediamine
  参考文献：
  名称：

  Antiprion activity of functionalized 9-aminoacridines related to quinacrine

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2008.05.060

文献信息

• Burckhalter et al., Journal of the American Chemical Society, 1943, vol. 65, p. 2013
  作者：Burckhalter et al.

  DOI：——

  日期：——
• Tamemasa, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1951, vol. 71, p. 285,288
  作者：Tamemasa

  DOI：——

  日期：——
• 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.