8-amino-5-(3,4-dichlorophenoxy)-6-methoxy-4-methylquinoline | 82333-43-5

• 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: 8-amino-5-(3,4-dichlorophenoxy)-6-methoxy-4-methylquinoline
• 英文别名: 8-Amino-5-[3,4-dichlorophenoxy]-6-methoxylepidine；5-(3,4-dichlorophenoxy)-6-methoxy-4-methylquinolin-8-amine
• CAS: 82333-43-5
• 化学式: C₁₇H₁₄Cl₂N₂O₂
• 分子量: 349.216
• InChiKey: LGMMMSLCKZGPKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  57.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-amino-5-(3,4-dichlorophenoxy)-6-methoxy-4-methylquinoline 在 sodium tetrahydroborate 、 一水合肼 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 (+/-)-8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3,4-dichlorophenoxy]quinoline succinate
  参考文献：
  名称：

  Inhibition of human monoamine oxidase A and B by 5-phenoxy 8-aminoquinoline analogs

  摘要：

  8-Aminoquinolines (8-AQs) are important class of anti-infective therapeutics. 5-Phenoxy 8-aminoquinoline analogs have shown improved metabolic stability compared to primaquine. In view or predictive role of monoamine oxidases (MAO) in metabolism of 8-aminoquinolines the 5-phenoxy analogs were evaluated in vitro for the inhibition of recombinant human MAO-A and MAO-B. The analogs were several folds more potent inhibitors of MAO-A and MAO-B compared to primaquine, the parent drug, with selectivity for MAO-B. 5-(4-Trifluoromethylphenoxy)-4-methylprimaquine (6) Inhibited MAO-B with IC50 value of 150 nM (626-fold more potent than primaquine). These results will have important implications in optimizing metabolic stability of 8-AQs to improve therapeutic value and also indicate scope for development of 8-AQs as selective MAO inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.108
• 作为产物：
  描述：

  3,4-二氯苯酚 在 盐酸 、 磷酸 、 palladium on activated charcoal 、 水 、 一水合肼 、 potassium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 8-amino-5-(3,4-dichlorophenoxy)-6-methoxy-4-methylquinoline
  参考文献：
  名称：

  Inhibition of human monoamine oxidase A and B by 5-phenoxy 8-aminoquinoline analogs

  摘要：

  8-Aminoquinolines (8-AQs) are important class of anti-infective therapeutics. 5-Phenoxy 8-aminoquinoline analogs have shown improved metabolic stability compared to primaquine. In view or predictive role of monoamine oxidases (MAO) in metabolism of 8-aminoquinolines the 5-phenoxy analogs were evaluated in vitro for the inhibition of recombinant human MAO-A and MAO-B. The analogs were several folds more potent inhibitors of MAO-A and MAO-B compared to primaquine, the parent drug, with selectivity for MAO-B. 5-(4-Trifluoromethylphenoxy)-4-methylprimaquine (6) Inhibited MAO-B with IC50 value of 150 nM (626-fold more potent than primaquine). These results will have important implications in optimizing metabolic stability of 8-AQs to improve therapeutic value and also indicate scope for development of 8-AQs as selective MAO inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.108

文献信息

• 8‐Aminoquinolines with an Aminoxyalkyl Side Chain Exert in vitro Dual‐Stage Antiplasmodial Activity
  作者：Michael Leven、Jana Held、Sandra Duffy、Leandro A. Alves Avelar、Stephan Meister、Michael Delves、David Plouffe、Krystina Kuna、Serena Tschan、Vicky M. Avery、Elizabeth A. Winzeler、Benjamin Mordmüller、Thomas Kurz

  DOI：10.1002/cmdc.201800691

  日期：2019.2.19

  A series of novel 8‐aminoquinolines (8‐AQs) with an aminoxyalkyl side chain were synthesized and evaluated for in vitro antiplasmodial properties against asexual blood stages, liver stages, and sexual stages of Plasmodium falciparum. 8‐AQs bearing 2‐alkoxy and 5‐phenoxy substituents on the quinoline ring system were found to be the most promising compounds under study, exhibiting potent blood schizontocidal

  合成了一系列具有氨氧基烷基侧链的新型8-氨基喹啉（8-AQs），并评估了其对恶性疟原虫无性血液阶段，肝脏阶段和性阶段的体外抗血浆特性。发现在喹啉环系统上带有2-烷氧基和5-苯氧基取代基的8-AQ是最有前途的化合物，在体外表现出强效的血吸虫病和中度组织吸虫病活性。
• 8-AMINOQUINOLINES
  申请人：——

  公开号：US20010007031A1

  公开（公告）日：2001-07-05

  It has been found that one of the enantiomers of 8-aminoquinoline antiparasitic compounds is surprisingly more active than the other enantiomer against parasitic infections including opportunistic parasitic infections. These enantiomers as well as pharmaceutical compositions containing pure enantiomers are disclosed. Also disclosed is a novel class of 8-aminoquinolines which contain a tri-substituted phenoxy substitution.

  已经发现，8-氨基喹啉抗寄生虫化合物的对映体之一比另一对映体在对抗寄生虫感染（包括机会性寄生虫感染）方面表现出更高的活性。这些对映体以及含有纯对映体的药物组合物已被披露。还披露了一类新型的含有三取代苯氧基取代的8-氨基喹啉。
• [EN] 8-AMINOQUINOLINES<br/>[FR] 8-AMINOQUINOLINES
  申请人：THE UNIVERSITY OF MISSISSIPPI

  公开号：WO1997036590A1

  公开（公告）日：1997-10-09

  (EN) It has been found that one of the enantiomers of 8-aminoquinoline antiparasitic compounds is surprisingly more active than the other enantiomer against parasitic infections including opportunistic parasitic infections. These enantiomers as well as pharmaceutical compositions containing pure enantiomers are disclosed. Also disclosed is a novel class of 8-aminoquinolines which contain a tri-substituted phenoxy substitution.(FR) On a découvert que l'un des énantiomères des composés antiparasitaires à base de 8-aminoquinolines est considérablement plus actif que les autres de ces énantiomères contre les infections parasitaires, y compris les infections parasitaires opportunistes. La présente invention concerne donc de tels énantiomères ainsi que des compositions pharmaceutiques contenant des énantiomères purs. L'invention concerne également une nouvelle classe de 8-aminoquinolines à substitution phénoxy trisubstitué.

  已经发现，8-氨基喹啉类抗寄生虫化合物的其中一种对寄生虫感染，包括机会性寄生虫感染，比另一种对映体表现出更强的活性。本发明揭示了这些对映体以及含有纯对映体的药物组合物。同时，本发明还揭示了一类新型的8-氨基喹啉类化合物，其中含有三取代苯氧基置换。
• 8-aminoquinolines
  申请人：The University of Mississippi

  公开号：US06376511B2

  公开（公告）日：2002-04-23

  It has been found that one of the enantiomers of 8-aminoquinoline antiparasitic compounds is surprisingly more active than the other enantiomer against parasitic infections including opportunistic parasitic infections. These enantiomers as well as pharmaceutical compositions containing pure enantiomers are disclosed. Also disclosed is a novel class of 8-aminoquinolines which contain a tri-substituted phenoxy substitution.

  研究发现，8-氨基喹啉类抗寄生虫化合物的对映体之一比另一对映体更有效，可用于治疗包括机会性寄生虫感染在内的寄生虫感染。本发明揭示了这些对映体以及含有纯对映体的药物组合物。还揭示了一类新的8-氨基喹啉类化合物，其中包含三取代苯氧基取代。
• Antimalarials. 14. 5-(Aryloxy)-4-methylprimaquine analogs. A highly effective series of blood and tissue schizonticidal agents
  作者：Maurice P. LaMontagne、Peter Blumbergs、Richard E. Strube

  DOI：10.1021/jm00351a017

  日期：1982.9

  A series of five 5-(aryloxy)-4-methylprimaquine analogues has been prepared and evaluated for antimalarial activity. The compounds were tested for suppressive activity against Plasmodium berghei in mice and for radical curative activity against Plasmodium cynomolgi in the rhesus monkey. The compounds were not only significantly superior to primaquine as radical curative agents but also were suprisingly highly effective as suppressive agents.