6-chloro-2-methoxy-N-(4-(4-methylpiperazin-1-yl)phenyl)acridin-9-amine | 1062073-54-4

• 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: 6-chloro-2-methoxy-N-(4-(4-methylpiperazin-1-yl)phenyl)acridin-9-amine
• 英文别名: 6-chloro-2-methoxy-N-[4-(4-methylpiperazin-1-yl)phenyl]acridin-9-amine
• CAS: 1062073-54-4
• 化学式: C₂₅H₂₅ClN₄O
• 分子量: 432.953
• InChiKey: NMDDEXFRYBASBH-UHFFFAOYSA-N

物化性质

• 熔点：
  190.9-192.2 °C
• 沸点：
  601.5±55.0 °C(Predicted)
• 密度：
  1.287±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  40.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-甲基-4-(4-硝基苯基)哌嗪 在 盐酸 、 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 生成 6-chloro-2-methoxy-N-(4-(4-methylpiperazin-1-yl)phenyl)acridin-9-amine
  参考文献：
  名称：

  在9-氨基位置带有碱性苯基残基的功能化奎纳克林类似物的抗-病毒活性和类药物潜力

  摘要：

  在本文中，我们报道了用4-（4-甲基哌嗪-1-基）苯基，（1-苄基哌啶-4- yl）及其结构变体。发现在不同different病毒感染的鼠细胞模型的效价和活性方面，一些有前途的类似物在抗病毒方面比奎纳克林更有利。它们还表现出对人类病毒蛋白片段的更高结合亲和力（hPrP 121–231）比奎纳克林高，并且在PAMPA-BBB分析中的渗透率在CNS渗透候选物范围内。当在过表达Pgp的细胞系上进行双向分析评估时，与奎纳克林相比，一种类似物对Pgp外排活性的敏感性较低。两者合计，结果表明连接到a啶，四氢ac啶和喹啉骨架上的取代9-氨基侧链的重要作用。该侧链的性质影响基于细胞的效能，PAMPA渗透性和对hPrP 121-231的结合亲和力。

  DOI：

  10.1016/j.ejmech.2011.04.016

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.
• Anti-prion activities and drug-like potential of functionalized quinacrine analogs with basic phenyl residues at the 9-amino position
  作者：Thuy Nguyen、Yuji Sakasegawa、Katsumi Doh-ura、Mei-Lin Go

  DOI：10.1016/j.ejmech.2011.04.016

  日期：2011.7

  In this paper, we report the synthesis and cell-based anti-prion activity of quinacrine analogs derived by replacing the basic alkyl side chain of quinacrine with 4-(4-methylpiperazin-I-yl)phenyl, (1-benzylpiperidin-4-yl) and their structural variants. Several promising analogs were found that have a more favorable anti-prion profile than quinacrine in terms of potency and activity across different

  在本文中，我们报道了用4-（4-甲基哌嗪-1-基）苯基，（1-苄基哌啶-4- yl）及其结构变体。发现在不同different病毒感染的鼠细胞模型的效价和活性方面，一些有前途的类似物在抗病毒方面比奎纳克林更有利。它们还表现出对人类病毒蛋白片段的更高结合亲和力（hPrP 121–231）比奎纳克林高，并且在PAMPA-BBB分析中的渗透率在CNS渗透候选物范围内。当在过表达Pgp的细胞系上进行双向分析评估时，与奎纳克林相比，一种类似物对Pgp外排活性的敏感性较低。两者合计，结果表明连接到a啶，四氢ac啶和喹啉骨架上的取代9-氨基侧链的重要作用。该侧链的性质影响基于细胞的效能，PAMPA渗透性和对hPrP 121-231的结合亲和力。