6-chloro-2-methoxy-9-(piperazin-1-yl)acridine | 1150591-97-1

• 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-9-(piperazin-1-yl)acridine
• 英文别名: 6-Chloro-2-methoxy-9-piperazin-1-yl-acridine；6-chloro-2-methoxy-9-piperazin-1-ylacridine
• CAS: 1150591-97-1
• 化学式: C₁₈H₁₈ClN₃O
• 分子量: 327.813
• InChiKey: XXLZVWIDRWGAER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  37.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-chloro-2-methoxy-9-(piperazin-1-yl)acridine 、 2-bromo-(10β-dihydroartemisinoxy)ethane 生成
  参考文献：
  名称：

  合成的青蒿素衍生物对利什曼原虫前鞭毛体的体外功效

  摘要：

  利什曼病是一种被忽视的热带疾病，在全世界影响着数千人，特别是在它与疟疾共存的发展中国家。临床上只有少数药物可用于治疗这种疾病，但严重的局限性威胁到它们的使用。因此，新的、安全和有效的药物，包括抗疟疾-利什曼病合并感染的药物，势在必行。我们评估了先前合成的强效抗疟青蒿素衍生物的体外抗感染潜力。具有 1,1'-联苯和苯硫基部分的类似酯比临床青蒿素对多诺瓦尼疟原虫的效力高 30 倍，使它们有资格作为抗前鞭毛体命中物，以进一步研究寻找疟疾-利什曼病共感染疗法。

  DOI：

  10.1016/j.bmcl.2020.127581
• 作为产物：
  描述：

  哌嗪 、 6,9-二氯-2-甲氧基吖啶 在 苯酚 作用下， 生成 6-chloro-2-methoxy-9-(piperazin-1-yl)acridine
  参考文献：
  名称：

  Antitumour and antimalarial activity of artemisinin–acridine hybrids

  摘要：

  Artemisinin-acridine hybrids were prepared and evaluated for their in vitro activity against tumour cell lines and a chloroquine sensitive strain of Plasmodium falciparum. They showed a 2-4-fold increase in activity against HL60, MDA-MB-231 and MCF-7 cells in comparison with dihydroartemisinin (DHA) and moderate antimalarial activity. Strong evidence that the compounds induce apoptosis in HL60 cells was obtained by flow cytometry, which indicated accumulation of cells in the G1 phase of the cell cycle. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.02.028

文献信息

• Semi-synthetic and synthetic 1,2,4-trioxaquines and 1,2,4-trioxolaquines: synthesis, preliminary SAR and comparison with acridine endoperoxide conjugates
  作者：Nuna C.P. Araújo、Victoria Barton、Michael Jones、Paul A. Stocks、Stephen A. Ward、Jill Davies、Patrick G. Bray、Alison E. Shone、Maria L.S. Cristiano、Paul M. O’Neill

  DOI：10.1016/j.bmcl.2009.02.013

  日期：2009.4

  A novel series of semi-synthetic trioxaquines and synthetic trioxolaquines were prepared, in moderate to good yields. Antimalarial activity was evaluated against both the chloroquine-sensitive 3D7 and resistant K1 strain of Plasmodium falciparum and both series of compounds were shown to be active in the low nanomolar range. For comparison the corresponding 9-amino acridine analogues were also prepared and shown to have low nanomolar activity like their quinoline counterparts. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis and in vitro biological evaluation of aminoacridines and artemisinin–acridine hybrids
  作者：Juan P. Joubert、Frans J. Smit、Lissinda du Plessis、Peter J. Smith、David D. N’Da

  DOI：10.1016/j.ejps.2014.01.014

  日期：2014.6

  During this study, 9-aminoacridine and artemisinin-acridine hybrid compounds were synthesized and the in vitro for antimalarial activity against both the chloroquine sensitive but also gametocytocidal strain (NF54), and chloroquine resistant (Dd2) strains of Plasmodium fakiparum was determined. In vitro cytotoxicity against CHO cells, apoptosis of HepG2 and SH-SY5Y as well as anticancer activity against HeLa cell lines were assessed. The hybrids were synthesized, using a microwave-assisted radiation method by covalently linking artemisinin and acridine pharmacophores by means of a liable, aminoethyl ether linker. The synthesized compounds were found active against both the Plasmodium strains and displayed superior selective toxicity towards the parasitic cells. Hybrid 7, however, containing ethylenediamine linker, proved the most active of all of the synthesized compounds. It had seven-fold higher antigametocytocidal activity compared to chloroquine and was also found to be seven-fold more potent than chloroquine against the Dd2 strain, with highly selective action towards the parasitic cells. This hybrid also showed favourable anti-cancer activity against the HeLa cells, three-and eight-fold higher than those of chloroquine and melphalan, respectively. This hybrid may therefore stand as drug candidate for further investigation in the search for new and effective drugs against malaria and cervical cancer. (C) 2014 Elsevier B.V. All rights reserved.