N¹,N¹-diethyl-N⁴-(7-trifluoromethylquinolin-4-yl)pentyl-1,4-diamine | 442-85-3

• 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,N¹-diethyl-N⁴-(7-trifluoromethylquinolin-4-yl)pentyl-1,4-diamine
• 英文别名: N⁴,N⁴-diethyl-1-methyl-N¹-(7-trifluoromethyl-[4]quinolyl)-butanediyldiamine；N⁴,N⁴-Diaethyl-1-methyl-N¹-(7-trifluormethyl-[4]chinolyl)-butandiyldiamin；Diethyl(4-{[7-(trifluoromethyl)(4-quinolyl)]amino}pentyl)amine；1-N,1-N-diethyl-4-N-[7-(trifluoromethyl)quinolin-4-yl]pentane-1,4-diamine
• CAS: 442-85-3
• 化学式: C₁₉H₂₆F₃N₃
• 分子量: 353.431
• InChiKey: HIWSRDNBRUFDDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  N¹,N¹-diethyl-N⁴-(7-trifluoromethylquinolin-4-yl)pentyl-1,4-diamine 在 D-樟脑酸 、 sodium ethanolate 作用下， 以 乙醇 、 乙酸乙酯 、 甲醇 为溶剂， 反应 1.0h， 以64%的产率得到(S)-N¹,N¹-diethyl-N⁴-(7-trifluoromethylquinolin-4-yl)pentyl-1,4-diamine
  参考文献：
  名称：

  光学活性氯喹和羟氯喹及其类似物、其制备方法、组合物和用途

  摘要：

  本发明提供一种制备光学活性氯喹和羟氯喹及其类似物的快速和简便的方法，将氯喹和羟氯喹及其类似物的消旋体与酸性手性拆分试剂反应生成相应的盐，经分离纯化后得到光学纯的氯喹和羟氯喹及其类似物的盐，再将其与碱反应得到高光学纯度的(R)‑或(S)‑氯喹和(R)‑或(S)‑羟氯喹及其类似物。此方法操作简便，成本较低，对映体纯度可达99.9％ee，易实现单一手性构型‑氯喹和羟氯喹及其类似物的工业化生产。本发明还提供一种(R)‑或(S)‑氯喹和(R)‑或(S)‑羟氯喹及其类似物、其药物组合物和用途，光学活性的氯喹和羟氯喹及其类似物降低了毒副作用，对冠状病毒、流感病毒和自身免疫性疾病具有更好的治疗效果。

  公开号：

  CN112457244A
• 作为产物：
  描述：

  7-（三氯甲基）-4-羟基喹啉 在 五氯化磷 、 三氯氧磷 作用下， 生成 N¹,N¹-diethyl-N⁴-(7-trifluoromethylquinolin-4-yl)pentyl-1,4-diamine
  参考文献：
  名称：

  Synthesis of 4-Hydroxyquinolines. VIII. Some Halogen Containing 4-Aminoquinoline Derivatives¹

  摘要：

  DOI：

  10.1021/ja01194a061

文献信息

• Synthesis of ring-substituted 4-aminoquinolines and evaluation of their antimalarial activities
  作者：Peter B. Madrid、John Sherrill、Ally P. Liou、Jennifer L. Weisman、Joseph L. DeRisi、R. Kiplin Guy

  DOI：10.1016/j.bmcl.2004.12.037

  日期：2005.2

  A simple two-step synthesis method was used to make 51 B-ring-substituted 4-hydroxyquinolines allowing analysis of the effect of ring substitutions on inhibition of growth of chloroquine sensitive and resistant strains of Plasmodium falciparum, the dominant cause of malaria morbidity. Substituted quinoline rings other than the 7-chloroquinoline ring found in chloroquine were found to have significant activity against the drug-resistant strain of P. falciparum W2. (C) 2004 Elsevier Ltd. All rights reserved.
• Structure−Activity Relationships for Antiplasmodial Activity among 7-Substituted 4-Aminoquinolines
  作者：Dibyendu De、Frances M. Krogstad、Larry D. Byers、Donald J. Krogstad

  DOI：10.1021/jm980146x

  日期：1998.12.1

  Aminoquinolines (AQs) with diaminoalkane side chains (-HNRNEt2) shorter or longer than the isopentyl side chain [-HNCHMe(CH2)(3)NEt2] of chloroquine are active against both chloroquine-susceptible and -resistant Plasmodium falciparum. (De, D.; et al. Am. J. Trop. Med. Hyg. 1996, 55, 579-583). In the studies reported here, we examined structure-activity relationships (SARs) among AQs with different N,N-diethyldiaminoalkane side chains and different substituents at the 7-position occupied by Cl in chloroquine. 7-Iodo- and 7-bromo-AQs with diaminoalkane side chains [-HN(CH2)(2)NEt2, -HN(CH2)(3)NEt2, or -HNCHMeCH2NEt2] were as active as the corresponding 7-chloro-AQs against both chloroquine-susceptible and -resistant P. falciparum (IC(50)s of 3-12 nM). In contrast, with one exception, 7-fluoro-AQs and 7-trifluoromethyl-AQs were less active against chloroquine-susceptible P. falciparum (IC(50)s of 15-50 nM) and substantially less active against chloroquine-resistant P. falciparum (IC(50)s of 18-500 nM). Furthermore, most 7-OMe-AQs were inactive against both chloroquine-susceptible (IC(50)s of 17-150 nM) and -resistant P. falciparum (IC(50)s of 90-3000 nM).
• Trifluoromethylated Quinolines
  作者：Aram. Mooradian、C. M. Suter

  DOI：10.1021/ja01178a072

  日期：1949.10
• DE683692
  申请人：——

  公开号：——

  公开（公告）日：——
• Structure−Function Correlation of Chloroquine and Analogues as Transgene Expression Enhancers in Nonviral Gene Delivery
  作者：Jianjun Cheng、Ryan Zeidan、Swaroop Mishra、Aijie Liu、Suzie H. Pun、Rajan P. Kulkarni、Gregory S. Jensen、Nathalie C. Bellocq、Mark E. Davis

  DOI：10.1021/jm060736s

  日期：2006.11.1

  To understand how chloroquine (CQ) enhances transgene expression in polycation-based, nonviral gene delivery systems, a number of CQ analogues with variations in the aliphatic amino side chain or in the aromatic ring are synthesized and investigated. Our studies indicate that the aliphatic amino moiety of CQ is essential to provide increased gene expression. Further, the enhancements are more dramatically affected by changes to the aromatic ring and are positively correlated to the strength of intercalation between DNA and the CQ analogues. Quinacrine (QC), a CQ analogue with a fused acridinyl structure that can strongly intercalate DNA, enhances transfection similarly to CQ at a concentration 10 times lower, while N-4-(4-pyridinyl)-N-1, N-1-diethyl-1,4-pentanediamine (CP), a CQ analogue that has a weakly intercalating pyridinyl ring, shows no effect on gene expression. Subtle change on the 7-substituent of the chloroquine aromatic structure can also greatly affect the ability of the CQ analogues to enhance transgene expression. Transfection in the presence of N-4-(7-trifluoromethyl-4-quinolinyl)-N-1, N-1-diethyl-1,4-pentanediamin e (CQ7a) shows expression efficiency 10 times higher than in the presence of CQ at same concentration, while transfection in the presence of N-4-(4-quinolinyl)-N-1, N-1-diethyl-1,4-pentanediamine (CQ7b) does not reveal any enhancing effects on expression. Through a number of comparative studies with CQ and its analogues, we conclude that there are at least three mechanistic features of CQ that lead to the enhancement in gene expression: (i) pH buffering in endocytic vesicles, (ii) displacement of polycations from the nucleic acids in polyplexes, and (iii) alteration of the biophysical properties of the released nucleic acid.