{3-[4-(3-aminopropylamino)butylamino]propyl}(3,7,11-trimethyldodeca-2,6,10-trienyl)amine | 1394833-44-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: {3-[4-(3-aminopropylamino)butylamino]propyl}(3,7,11-trimethyldodeca-2,6,10-trienyl)amine
• 英文别名: N-(3-aminopropyl)-N'-[3-(3,7,11-trimethyldodeca-2,6,10-trienylamino)propyl]butane-1,4-diamine
• CAS: 1394833-44-3
• 化学式: C₂₅H₅₀N₄
• 分子量: 406.699
• InChiKey: GCXVUAWOJZJDFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  20
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  62.1
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  {3-[4-(3-aminopropylamino)butylamino]propyl}(3,7,11-trimethyldodeca-2,6,10-trienyl)amine 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 NV₇₁₆
  参考文献：
  名称：

  Characterization of a new aerosol antibiotic/adjuvant combination for the treatment of P. aeruginosa lung infections

  摘要：

  The lack of novel classes of antibiotics as well as the constant increase of multidrug resistant bacteria are leaving the clinicians disarmed to treat bacterial infections, especially those caused by Gram-negative pathogens. Among all the investigated solutions, the design of adjuvants able to enhance antibiotics activities appears to be one of the most promising. In this context, a polyamino-isoprenyl derivative has been recently identified to be able to potentiate, at a very low concentration the activity of doxycycline against P. aeruginosa bacterial strains by increasing its intracellular concentration. On the other hand, since aerosol therapy allows a rapid drug administration and targets the respiratory system by avoiding the first pass effect and minimizing undesirable systemic effects, we have developed the first adjuvant/antibiotic combination in an aerosolized form and demonstrated the feasibility of such an approach. Thus, combination aerosol droplets have been demonstrated in sizes suitable for inhalation (3.4 and 4.4 mu m mass median aerodynamic diameter and 54 and 60% of the aerodynamic particle size distribution less than 5 mu m, as measured for the adjuvant NV716 and doxycycline, respectively and with properties (stoichiometric 1:1 ratio of NV716 salt to drug) that would support further development as an inhaled dosage form. Taken together, our results suggest that these molecules could be successfully delivered at the requested concentration in the lungs and then able to decrease drug consumption as well as increase treatment efficacy.

  DOI：

  10.1016/j.ijpharm.2020.119548
• 作为产物：
  描述：

  精胺 、 法呢基氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以64%的产率得到{3-[4-(3-aminopropylamino)butylamino]propyl}(3,7,11-trimethyldodeca-2,6,10-trienyl)amine
  参考文献：
  名称：

  Efficiency of a Tetracycline-Adjuvant Combination Against Multidrug Resistant Pseudomonas aeruginosa Tunisian Clinical Isolates

  摘要：

  突尼斯的多重耐药菌株数量不断增加，已成为严重的健康问题，导致死亡率和发病率高。由于当前的抗生素正在迅速失效，需要新的对抗耐药性的策略。最近，我们证明了四环素类抗生素与各种多聚胺异戊烯基辅助剂的组合可以延长这些药物对绿脓杆菌参考菌株（PA01）的寿命并增强其活性。在我们持续研究的背景下，我们对抗生素-辅助剂有效方法针对从突尼斯军事医院收集的大量绿脓杆菌临床菌株进行了研究。在本文中，我们证明了在多西环素或米诺环素存在下，使用浓度在2.5至10微米范围内的法尼烯精胺化合物3的组合可以显著降低绿脓杆菌对抗生素的耐药性。

  DOI：

  10.3390/antibiotics9120919

文献信息

• First evidence for the use of polyamines as nucleophiles in a regioselective palladium-catalyzed allylic amination reaction
  作者：Cyril Pieri、Sébastien Combes、Jean Michel Brunel

  DOI：10.1016/j.tet.2014.10.019

  日期：2014.12

  Palladium-catalyzed reaction of unsymmetrical allylic electrophiles with polyamines gives rise to regioisomeric allylic polyamines. An original catalytic procedure providing an efficient method for the regioselective synthesis of new classes of polyamino derivatives of biological interest is reported. Based on experimental considerations, a mechanistic rationale involving a thermodynamically controlled

  钯催化的不对称烯丙基亲电子试剂与多胺的反应产生了区域异构的烯丙基多胺。报道了一种原始的催化方法，该方法为区域选择性合成具有生物学意义的新型聚氨基衍生物提供了一种有效的方法。基于实验考虑，提出了一种机械原理，其中涉及对最初形成的支链产物进行热力学控制的异构化，以解决所观察到的总区域选择性。
• Characterization of a new aerosol antibiotic/adjuvant combination for the treatment of P. aeruginosa lung infections
  作者：Hana Douafer、Véronique Andrieu、Emmanuel Wafo、Jean Michel Brunel

  DOI：10.1016/j.ijpharm.2020.119548

  日期：2020.8

  The lack of novel classes of antibiotics as well as the constant increase of multidrug resistant bacteria are leaving the clinicians disarmed to treat bacterial infections, especially those caused by Gram-negative pathogens. Among all the investigated solutions, the design of adjuvants able to enhance antibiotics activities appears to be one of the most promising. In this context, a polyamino-isoprenyl derivative has been recently identified to be able to potentiate, at a very low concentration the activity of doxycycline against P. aeruginosa bacterial strains by increasing its intracellular concentration. On the other hand, since aerosol therapy allows a rapid drug administration and targets the respiratory system by avoiding the first pass effect and minimizing undesirable systemic effects, we have developed the first adjuvant/antibiotic combination in an aerosolized form and demonstrated the feasibility of such an approach. Thus, combination aerosol droplets have been demonstrated in sizes suitable for inhalation (3.4 and 4.4 mu m mass median aerodynamic diameter and 54 and 60% of the aerodynamic particle size distribution less than 5 mu m, as measured for the adjuvant NV716 and doxycycline, respectively and with properties (stoichiometric 1:1 ratio of NV716 salt to drug) that would support further development as an inhaled dosage form. Taken together, our results suggest that these molecules could be successfully delivered at the requested concentration in the lungs and then able to decrease drug consumption as well as increase treatment efficacy.
• Efficiency of a Tetracycline-Adjuvant Combination Against Multidrug Resistant Pseudomonas aeruginosa Tunisian Clinical Isolates
  作者：Azza Troudi、Meha Fethi、Mohamed Selim El Asli、Jean Michel Bolla、Naouel Klibi、Jean Michel Brunel

  DOI：10.3390/antibiotics9120919

  日期：——

  The growing number of multidrug resistant strains in Tunisia has become a serious health concern contributing to high rate of mortality and morbidity. Since current antibiotics are rapidly becoming ineffective, novel strategies to combat resistance are needed. Recently, we demonstrated that combination of a tetracycline antibiotic with various polyaminoisoprenyl adjuvants can sustain the life span and enhance the activity of these drugs against Pseudomonas aeruginosa reference strain (PA01). In the context of our continuing studies, the effective approach of antibiotic-adjuvant was investigated against a large panel of P. aeruginosa Tunisian clinical strains collected from the Military Hospital of Tunis. In this paper, we demonstrated that the combination of a farnesyl spermine compound 3 used at concentrations ranging from 2.5 to 10 µM, in the presence of doxycycline or minocycline leads to a significant decrease of P. aeruginosa antibiotic resistance.

  突尼斯的多重耐药菌株数量不断增加，已成为严重的健康问题，导致死亡率和发病率高。由于当前的抗生素正在迅速失效，需要新的对抗耐药性的策略。最近，我们证明了四环素类抗生素与各种多聚胺异戊烯基辅助剂的组合可以延长这些药物对绿脓杆菌参考菌株（PA01）的寿命并增强其活性。在我们持续研究的背景下，我们对抗生素-辅助剂有效方法针对从突尼斯军事医院收集的大量绿脓杆菌临床菌株进行了研究。在本文中，我们证明了在多西环素或米诺环素存在下，使用浓度在2.5至10微米范围内的法尼烯精胺化合物3的组合可以显著降低绿脓杆菌对抗生素的耐药性。