N-(7-chloroquinolin-4-yl)-2,2-dimethylpropane-1,3-diamine | 14046-78-7

• 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-(7-chloroquinolin-4-yl)-2,2-dimethylpropane-1,3-diamine
• 英文别名: N-(7-chloroqinolin-4-yl)-2,2-dimethylpropane-1,3-diamine；N1-(7-chloro-4-quinolyl)-2,2-dimethyl-1,3-propanediamine；7-Chloro-4-(3-amino-2,2-dimethlpropylamino)quinoline；N'-(7-chloroquinolin-4-yl)-2,2-dimethylpropane-1,3-diamine
• CAS: 14046-78-7
• 化学式: C₁₄H₁₈ClN₃
• mdl: MFCD25191872
• 分子量: 263.77
• InChiKey: LHKDUDGIPVLGDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.357
• 拓扑面积：
  50.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  二茂铁甲醛 、 N-(7-chloroquinolin-4-yl)-2,2-dimethylpropane-1,3-diamine 在 sodium borohydride 、 NaOH 作用下， 以 甲醇 为溶剂， 生成 N-(7-chloro-4-quinolyl)-N′-ferrocenyl-2,2-dimethylpropane-1,3-diamine
  参考文献：
  名称：

  1,2-二取代的二茂铁基碳水化合物氯喹偶联物可能作为抗疟药†

  摘要：

  这项工作提出了一个新的有机金属抗疟化合物家族，包括 二茂铁在环戊二烯基支架上以1，2-取代方式带有氯喹衍生的部分以及1,2; 3,5-二异亚丙基葡糖呋喃糖部分。合成途径是通过将二茂铁羧醛立体选择性官能化为1,2-二取代的共轭物而进行的。在对这些新的三功能结合物进行完全表征后，检查了它们在两种癌细胞系（MDA-MB-435S和Caco2）和一种非癌细胞系（MCF-10A）中的细胞毒性，表明可以观察到增加的细胞毒性与它们的碳水化合物取代的前体相比，氯喹二茂铁基共轭物具有更大的可比性。结合物在恶性疟原虫氯喹敏感菌株中的抗血浆活性（D10）和抗氯喹菌株（Dd2）被确定。单取代的缀合物13，14和15显示出降低的活性随二茂铁和喹啉部分之间的烷基链长度，双功能偶联物16，17，18示出恒定的活性，进行优于氯喹 在Dd2株中。

  DOI：

  10.1039/c2dt12050j
• 作为产物：
  描述：

  4,7-二氯喹啉 、 二甲基丙二胺 反应 5.0h， 以63%的产率得到N-(7-chloroquinolin-4-yl)-2,2-dimethylpropane-1,3-diamine
  参考文献：
  名称：

  Probing the Role of the Covalent Linkage of Ferrocene into a Chloroquine Template

  摘要：

  A new therapeutic approach to malaria led to the discovery of ferroquine (FQ, SR97276). To assess the importance of the linkage of the ferrocenyl group to a 4-aminoquinoline scaffold, two series of 4-aminoquinolines, structurally related to FQ, were synthesized. Evaluation of antimalarial activity, physicochemical parameters, and the beta-hematin inhibition property indicate that the ferrocene moiety has to be covalently flanked by a 4-aminoquinoline and an alkylamine. Current data reinforced our choice of FQ as a drug candidate.

  DOI：

  10.1021/jm060259d

文献信息

• 1,2-Disubstituted ferrocenyl carbohydrate chloroquine conjugates as potential antimalarial agents
  作者：Christoph Herrmann、Paloma F. Salas、Brian O. Patrick、Carmen de Kock、Peter J. Smith、Michael J. Adam、Chris Orvig

  DOI：10.1039/c2dt12050j

  日期：——

  This work presents a new family of organometallic antimalarial compounds consisting of ferrocene bearing a chloroquine-derived moiety as well as a 1,2;3,5-diisopropylidene glucofuranose moiety at a cyclopentadienyl scaffold in a 1,2-substitution pattern. The synthetic route proceeds via a stereoselective functionalization of ferrocene carboxaldehyde to the 1,2-disubstituted conjugates. After complete

  这项工作提出了一个新的有机金属抗疟化合物家族，包括 二茂铁在环戊二烯基支架上以1，2-取代方式带有氯喹衍生的部分以及1,2; 3,5-二异亚丙基葡糖呋喃糖部分。合成途径是通过将二茂铁羧醛立体选择性官能化为1,2-二取代的共轭物而进行的。在对这些新的三功能结合物进行完全表征后，检查了它们在两种癌细胞系（MDA-MB-435S和Caco2）和一种非癌细胞系（MCF-10A）中的细胞毒性，表明可以观察到增加的细胞毒性与它们的碳水化合物取代的前体相比，氯喹二茂铁基共轭物具有更大的可比性。结合物在恶性疟原虫氯喹敏感菌株中的抗血浆活性（D10）和抗氯喹菌株（Dd2）被确定。单取代的缀合物13，14和15显示出降低的活性随二茂铁和喹啉部分之间的烷基链长度，双功能偶联物16，17，18示出恒定的活性，进行优于氯喹 在Dd2株中。
• 1,1′-Disubstituted Ferrocenyl Carbohydrate Chloroquine Conjugates as Potential Antimalarials
  作者：Christoph Herrmann、Paloma F. Salas、Jacqueline F. Cawthray、Carmen de Kock、Brian O. Patrick、Peter J. Smith、Michael J. Adam、Chris Orvig

  DOI：10.1021/om300354x

  日期：2012.8.27

  This work presents a new class of organometallic antimalarials, based on a ferrocene scaffold, bearing a chloroquine derivative and a 1,2;3,5-(diisopropylidene)-alpha-D-glucofuranose moiety in a 1,1'-heteroannular substitution pattern. Synthesis proceeds via orthogonal functionalization of ferrocene, giving 1-acetoxy-1'-(1,3-dioxan-2-yl)ferrocene (15) as the precursor for modular introduction of the carbohydrate (16, 17) followed by subsequent reductive amination with chloroquine building blocks 8-10, yielding the 1-[3-(7-chloroquinolin-4-ylamino)alkylamino]-1'-[6-(1,2;3,5-diisopropylidene)-alpha-D-glucofuranosidyl]ferrocenes 18-20. After complete characterization of these new, trifunctional conjugates, they were examined for their antiplasmodial activity in a chloroquine-susceptible strain of Plasmodium falciparum (D10) and in two chloroquine-resistant strains (Dd2 and K1). Their activity was compared to that of the monosubstituted reference conjugates 1-3 and the 1,2-disubstituted regioisomers 4-6. Compounds 19 and 20 exhibited consistently high activity in in vitro antiplasmodial activity assays performed in Dd2 and K1 strains, performing better than the reference compounds chloroquine and the monosubstituted and 1,2-disubstituted compounds 1-6.
• Probing the Role of the Covalent Linkage of Ferrocene into a Chloroquine Template
  作者：Christophe Biot、Wassim Daher、Cheikh M. Ndiaye、Patricia Melnyk、Bruno Pradines、Natascha Chavain、Alain Pellet、Laurent Fraisse、Lydie Pelinski、Christian Jarry、Jacques Brocard、Jamal Khalife、Isabelle Forfar-Bares、Daniel Dive

  DOI：10.1021/jm060259d

  日期：2006.7.1

  A new therapeutic approach to malaria led to the discovery of ferroquine (FQ, SR97276). To assess the importance of the linkage of the ferrocenyl group to a 4-aminoquinoline scaffold, two series of 4-aminoquinolines, structurally related to FQ, were synthesized. Evaluation of antimalarial activity, physicochemical parameters, and the beta-hematin inhibition property indicate that the ferrocene moiety has to be covalently flanked by a 4-aminoquinoline and an alkylamine. Current data reinforced our choice of FQ as a drug candidate.
• Structural Characteristics of Chloroquine-Bridged Ferrocenophane Analogues of Ferroquine May Obviate Malaria Drug-Resistance Mechanisms
  作者：Paloma F. Salas、Christoph Herrmann、Jacqueline F. Cawthray、Corinna Nimphius、Alexander Kenkel、Jessie Chen、Carmen de Kock、Peter J. Smith、Brian O. Patrick、Michael J. Adam、Chris Orvig

  DOI：10.1021/jm301422h

  日期：2013.2.28

  Five compounds displaying an unprecedented binding mode of chloroquine to ferrocene through the bridging of the cyclopentadienyl rings were studied alongside their monosubstituted ferrocene analogues and organic fragments. The antiplasmodial activity was evaluated against strains of the malaria parasite (Plasmodium falciparum). While the chloroquine-bridged ferrocenyl derivatives were less active than their five monosubstituted ferrocenyl analogues, they retained activity in the drug-resistant strains. The biological and physical properties were correlated to antiplasmodial activity. Intramolecular hydrogen bonding was associated with increased antiplasmodial action, but it is not the determining factor. Instead, balance between lipophilicity and hydrophilicity had a greater influence. It was found that calculated partition coefficient (log P) values of 4.5-5.0 and topological polar surfaces area (tPSA) values of similar to 26.0 angstrom(2) give the best balance. The particular conformation, compact size, and lipophilicity/hydrophilicity balance observed in the bridged compounds provide them with the structural characteristics needed to escape the mechanisms responsible for resistance.
• Synthesis and in vitro antiplasmodial activity of ferrocenyl aminoquinoline derivatives
  作者：Gabin Mwande Maguene、Jean-Bernard Lekana-Douki、Elisabeth Mouray、Till Bousquet、Philippe Grellier、Sylvain Pellegrini、Fousseyni Samba Toure Ndouo、Jacques Lebibi、Lydie Pélinski

  DOI：10.1016/j.ejmech.2014.11.065

  日期：2015.1

  The aim of this study was to synthesize a series of ferrocenyl 4-aminoquinolines and to evaluate their activities against Plasmodium falciparum F32 (chloroquine-sensitive) and FCB1 and K1 (chloroquino-resistant). Some of the ferrocenyl compounds exhibited in vitro antiplasmodial activity in the nM range. In particular, (1R,4R)-N1-(7-chloroquinolin-4-yl)-N4-(ferrocenylmethyl)-N4-methylcyclohexane-1,4-diamine 17 presented the lowest IC50 value (26 nM) against CQ-resistant strains. (C) 2014 Elsevier Masson SAS. All rights reserved.