N¹,N²-bis(4-fluorobenzyl)ethane-1,2-diamine | 1581-26-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N¹,N²-bis(4-fluorobenzyl)ethane-1,2-diamine
• 英文别名: N,N'-bis[(4-fluorophenyl)methyl]ethane-1,2-diamine
• CAS: 1581-26-6
• 化学式: C₁₆H₁₈F₂N₂
• 分子量: 276.329
• InChiKey: NKQDOFJPPIPZPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  24.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N¹,N²-bis(4-fluorobenzyl)ethane-1,2-diamine 在 六氯环三磷腈 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 57.0h， 生成 7,10-bis(4-fluorobenzyl)-2,2,4,4-tetra-1,4-dioxa-8-azaspiro[4.5]dec-8-yl-1,3,5,7,10-pentaaza-2λ5,4λ5,6λ5-triphosphaspiro[4.5]deca-1,3,5-triene
  参考文献：
  名称：

  Phosphorus–nitrogen compounds part 22. Syntheses, structural investigations, biological activities and DNA interactions of new mono and bis (4-fluorobenzyl) spirocyclophosphazenes

  摘要：

  The reactions of hexachlorocyclotriphosphazene, N3P3Cl6, with mono (1 and 2) and bis(4-fluorobenzyl) diamines (3-5), FPhCH2NH(CH2)(n)NHR (R=H or FPhCH2-), produce mono (1a and 2a) and bis(4-fluorobenzyl) monospirocyclophosphazenes (3a-5a). The tetraaminomonospirocyclophosphazenes (1b-2d) are obtained from the reactions of the partly substituted phosphazenes (1a and 2a) with excess pyrrolidine, morpholine and 1,4-dioxa-8-azaspiro[4,5]decane (DASD), respectively. The tetrachlorobis(4-fluorobenzyl) monospirocyclophosphazenes (4a and 5a) with excess pyrrolidine, morpholine and DASD afford the fully substituted bis(4-fluorobenzyl) monospirocyclophosphazenes (4b, 4d-5d) in boiling THF. In addition, monochlorobis(4-fluorobenzyl) monospirocyclophosphazenes (4e and 41) have also been isolated from the reactions with excess morpholine and DASD in boiling THF. The structural investigations of the compounds have been verified by elemental analyses, MS. FTIR, H-1, C-13, F-19 (for 1d and 2d). P-31 NMR, HSQC and HMBC techniques. The crystal structures of 3a, 4a, 5a and 2b have been determined by X-ray crystallography. The compounds 2a-5a, 1b-2d, 4b, 4d-5d, 4e and 41 have been screened for antibacterial effects on bacteria and for antifungal activity against yeast strains. The compounds 1b and 4b showed antimicrobial activity against three species of bacteria, Bacillus subtilis, Bacillus cereus and Staphylococcus aureus, and two fungi, Candida albicans and Candida tropicalis. Minimum inhibitory concentrations (MIC) were determined for 1b and 4b. The MIC values were found to be 5000 mu M for each bacteria. The most effective compound, 4b has exhibited activity with a MIC of 312 mu M for C albicans and 625 mu M for C. tropicalis. DNA-binding and the nature of the interaction with pBR322 plasmid DNA are studied. All of the compounds induce changes on the DNA mobility and intensity. Prevention of Hind[l] digestion with the compounds indicates that the compounds bind with AT nucleotides in DNA. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.poly.2011.08.035
• 作为产物：
  描述：

  对氟苯甲醛 在 sodium tetrahydroborate 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 苯 为溶剂， 反应 11.0h， 生成 N¹,N²-bis(4-fluorobenzyl)ethane-1,2-diamine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Substituted-Imidazolidine Derivatives

  摘要：

  研究人员合成了一系列较新的取代咪唑烷衍生物 3a-k，并对其进行了体内试验，以研究它们的抗炎、镇痛和抗溃疡活性。生物学评价结果表明，4-[1,3-双（4-羟基-3-甲氧基苄基）-2-咪唑烷基]苯二乙胺（3g）、4-[1、3-双（3-乙氧基-4-羟基苄基）-2-咪唑烷基]苯基二乙胺（3h）和 4-（1,3-双（苯并[d][1,3]二恶茂-5-基甲基）-4-甲基咪唑烷-2-基）-N,N-二乙基苯胺（3j）具有良好的抗炎和镇痛作用。此外，与标准药物相比，这些衍生物在低严重指数方面显示出更优越的胃肠道安全性。这些结果经统计学处理，具有重要意义。

  DOI：

  10.5012/jkcs.2013.57.2.227

文献信息

• Enantioselective Organocatalytic Synthesis of 2-Oxopiperazines from Aldehydes: Identification of the Elusive Epoxy Lactone Intermediate
  作者：Nikolaos Kaplaneris、Constantinos Spyropoulos、Maroula G. Kokotou、Christoforos G. Kokotos

  DOI：10.1021/acs.orglett.6b02699

  日期：2016.11.18

  organocatalytic linchpin catalysis approach was envisaged to convert simple aldehydes into enantioenriched 2-oxopiperazines. A four-step reaction sequence (chlorination, oxidation, substitution, and cyclization) was developed and led to different substitution patterns in high yields and selectivities. The reaction mechanism was studied, and the previously elusive epoxy lactone intermediate was identified by

  设想了一种有机催化的关键催化方法，将简单的醛转化为对映体富集的2-氧代哌嗪。开发了四步反应序列（氯化，氧化，取代和环化），并以高收率和选择性导致了不同的取代方式。研究了反应机理，并通过HRMS鉴定了以前难以捉摸的环氧内酯中间体。
• Systematic research of H2dedpa derivatives as potent inhibitors of New Delhi Metallo-β-lactamase-1
  作者：De-Yun Cui、Yi Yang、Meng-Meng Bai、Jiang-Xue Han、Cong-Cong Wang、Hong-Tao Kong、Bo-Yuan Shen、Da-Chao Yan、Chun-Ling Xiao、Yi-Shuang Liu、En Zhang

  DOI：10.1016/j.bioorg.2020.103965

  日期：2020.8

  New Delhi Metallo-β-lactamase-1 (NDM-1), a Zn (II)-dependent enzyme, can catalyze the hydrolysis of almost all β-lactam antibiotics including carbapenems, resulting in bacterial antibiotic resistance, which threatens public health globally. Based on our finding that H2dedpa is as an efficient NDM-1 inhibitor, a series of H2dedpa derivatives was systematically prepared. These compounds exhibited significant

  新德里Metallo-β-内酰胺酶-1（NDM-1）是一种依赖锌（II）的酶，可以催化几乎所有β-内酰胺抗生素（包括碳青霉烯）的水解，导致细菌对抗生素的耐药性，这在全球范围内威胁着公众健康。基于我们的发现，H 2 dedpa是有效的NDM-1抑制剂，系统地制备了一系列H 2 dedpa衍生物。这些化合物对NDM-1表现出显着的活性，IC 50值为0.06-0.94μM。在体外，化合物6k和6n可以恢复美罗培南对肺炎克雷伯菌，大肠杆菌和变形杆菌的活性。拥有NDM或IMP。特别地，当使用这两种化合物时，美罗培南对产生大肠杆菌的NDM-4的活性可提高至5333倍。基于时间杀伤的细胞分析表明，美罗培南与化合物6k或6n联合使用可杀死99.9％的奇异疟原虫。此外，化合物6k和6n具有非溶血性（HC 50  > 1280μg/ mL），并且对哺乳动物（HeLa）细胞毒性低。机理研究表明，化合物6k和6n通过螯合酶的Zn
• Synthesis and biological evaluation of novel cYY analogues targeting Mycobacterium tuberculosis CYP121A1
  作者：Safaa M. Kishk、Kirsty J. McLean、Sakshi Sood、Mohamed A. Helal、Mohamed S. Gomaa、Ismail Salama、Samia M. Mostafa、Luiz Pedro S. de Carvalho、Andrew W. Munro、Claire Simons

  DOI：10.1016/j.bmc.2019.02.051

  日期：2019.4

  The rise in multidrug resistant (MDR) cases of tuberculosis (TB) has led to the need for the development of TB drugs with different mechanisms of action. The genome sequence of Mycobacterium tuberculosis (Mtb) revealed twenty different genes coding for cytochrome P450s. CYP121A1 catalyzes a C-C crosslinking reaction of di-cyclotyrosine (cYY) producing mycocyclosin and current research suggests that either mycocyclosin is essential or the overproduction of cYY is toxic to Mtb. A series of 1,4-dibenzyl-2-imidazol-1-yl-methylpiperazine derivatives were designed and synthesised as cYY mimics. The derivatives substituted in the 4-position of the phenyl rings with halides or alkyl group showed promising antimycobacterial activity (MIC 6.25 mu g/mL), with the more lipophilic branched alkyl derivatives displaying optimal binding affinity with CYP121A1 (Pr-i K-D = 1.6 mu M; Bu-t K-D = 1.2 mu M). Computational studies revealed two possible binding modes within the CYP121A1 active site both of which would effectively block cYY from binding.