N-(4-aminobenzyl)-1,8-naphthalimide | 1419320-91-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: N-(4-aminobenzyl)-1,8-naphthalimide
• 英文别名: 2-(4-aminobenzyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione；2-[(4-aminophenyl)methyl]benzo[de]isoquinoline-1,3-dione
• CAS: 1419320-91-4
• 化学式: C₁₉H₁₄N₂O₂
• 分子量: 302.332
• InChiKey: WXANPFDWHXEMGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.22
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  63.4
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  苯磺酰氯 、 N-(4-aminobenzyl)-1,8-naphthalimide 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以52 %的产率得到N-(4-((1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)methyl)phenyl)benzenesulfonamide
  参考文献：
  名称：

  Inhibition Clathrin Mediated Endocytosis: Pitstop 1 and Pitstop 2 Chimeras

  摘要：

  Twenty‐five chimera compounds of Pitstop® 1 and 2 were synthesised and screened for their ability to block the clathrin terminal domain‐amphiphysin protein‐protein interaction (NTD‐PPI using an ELISA) and clathrin mediated endocytosis (CME) in cells.  Library 1 was based on Pitstop 2, but no notable clathrin PPI or in‐cell activity was observed.  With the Pitstop 1, 16 analogues were produced with 1,8‐naphthalic imide core as a foundation.  Analogues with methylene spaced linkers and simple amides showed a modest to good range of PPI inhibition (7.6 to 42.5 mM, naphthyl 39 and 4‐nitrophenyl 40 respectively) activity.  These data reveal the importance of the naphthalene sulfonate moiety, with no des‐SO3 analogue displaying PPI inhibition.  This was consistent with the observed analogue docked poses within the clathrin terminal domain Site 1 binding pocket.  Further modifications targeted the naphthalene imide moiety, with the installation of 5‐Br (45a), 5‐OH (45c) and 5‐propyl ether (45d) moieties.  Among them, the OH 45c and propyl ether 45d retained PPI inhibition, with propyl ether 45d being the most active with a PPI inhibition IC50 = 7.3 mM.  This is 2x more potent than Pitstop® 2 and 3x more potent than Pitstop 1.

  DOI：

  10.1002/cmdc.202400253
• 作为产物：
  描述：

  1,8-萘二甲酸酐 、 4-氨基苄胺 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 N-(4-aminobenzyl)-1,8-naphthalimide
  参考文献：
  名称：

  质子NMR谱表征新型氨基苄基邻苯二酰亚胺和相关酰亚胺及其对NO诱导的影响

  摘要：

  通过与氨基苄胺和三乙胺反应，将包括邻th啶在内的各种酸酐转变为相应的氨基苄基邻ari啶亚胺3a和类似的酰亚胺3b〜k（在邻位，间位和对位）。邻苯二甲酰亚胺3ao，3am和3ap的两个甲基侧链以及相关的酰亚胺具有两个以上的手性中心。当苄胺的氨基在邻位时，氢的孤电子对在H-NMR光谱中显示出不同的化学位移和耦合常数位置。这些邻苯二甲酰亚胺具有母体苯胺，吡啶和萘的平面结构，伯胺的亲核性和碱性可能反映了感应电子对化学位移的负面影响。我们通过将反应物Cantharidin 1a，脂族和芳族酸酐，伯苄基胺和苯胺衍生物加热到大约17.5 ℃，制备了cantharidinimides 。在高压密封管（Buchi glasuster 0032）中，用3 mL干甲苯和1-2 mL三乙胺在200°C的条件下以高收率生产邻苯二甲酰亚胺和类似物。的对位-aminobenzylic酰亚胺表明一氧化氮（NO）合成的更大

  DOI：

  10.1002/jccs.201400228

文献信息

• Modelling and Phenotypic Screening of NAP‐6 and 10‐Cl‐BBQ, AhR Ligands Displaying Selective Breast Cancer Cytotoxicity <i>in Vitro</i>
  作者：Jennifer R. Baker、Brett L. Pollard、Andrew J. S. Lin、Jayne Gilbert、Stefan Paula、Xiao Zhu、Jennette A. Sakoff、Adam McCluskey

  DOI：10.1002/cmdc.202000721

  日期：2021.5.6

  hydrocarbon receptor (AhR) pathway in developing breast‐cancer‐specific cytotoxic compounds, we examined the breast cancer selectivity and the docking pose of the AhR ligands (Z)‐2‐(2‐aminophenyl)‐1H‐benzo[de]isoquinoline‐1,3(2H)‐dione (NAP‐6; 5) and 10‐chloro‐7H‐benzo[de]benzo[4,5]imidazo[2,1‐a]isoquinolin‐7‐one (10‐Cl‐BBQ; 6). While the breast cancer selectivity of 5 in vitro is known, we discuss

  为了利用芳烃受体 (AhR) 通路在开发乳腺癌特异性细胞毒性化合物中的相互作用，我们检查了乳腺癌的选择性和 AhR 配体 ( Z )-2-(2-氨基苯基)-1的对接姿势ħ -苯并[ DE ]异喹啉-1,3（2 ħ） -二酮（NAP-6; 5）和10氯-7- ħ -苯并[ DE ]苯并[4,5]咪唑并[2,1-一个]异喹啉-7-one (10-Cl-BBQ; 6 )。虽然5 的体外乳腺癌选择性是已知的，但我们围绕这一先导讨论了 SAR，并通过使用表型细胞系筛选和 MTT 测定，首次表明6还具有乳腺癌选择性，特别是在三阴性（TN）受体乳腺癌细胞系 MDA-MB-468、ER+ 乳腺癌细胞系 T47D、ZR-75-1 和 HER2+ 乳腺癌细胞系 SKBR3（GI 50 个值分别为 0.098、0.97、0.13 和 0.21 μM）。事实上，6是55倍更有效在比正常MCF10A乳腺细胞（GI MDA-MB-468细胞50
• Development of 1,8-Naphthalimides as Clathrin Inhibitors
  作者：Kylie A. MacGregor、Mark J. Robertson、Kelly A. Young、Lisa von Kleist、Wiebke Stahlschmidt、Ainslie Whiting、Ngoc Chau、Phillip J. Robinson、Volker Haucke、Adam McCluskey

  DOI：10.1021/jm4015263

  日期：2014.1.9

  We reported the first small molecule inhibitors of the interaction between the clathrin N-terminal domain (TD) and endocyctic accessory proteins (i.e., clathrin inhibition(1)). Initial screening of a similar to 17 000 small molecule ChemBioNet library identified 1. Screening of an existing in-house propriety library identified four substituted 1,8-napthalimides as similar to 80-120 mu M clathrin inhibitors. Focused library development gave 3-sulfo-N-(4-aminobenzyl)-1,8-naphthalimide, potassium salt (18, IC50 approximate to 18 mu M). A second library targeting the 4-aminobenzyl moiety was developed, and four anogues displayed comparable activity (26, 27, 28, 34 with IC50 values of 22, 16, 15, and 15 mu M respectively) with a further four (24, 25, 32, 33) more active than 18 with IC50 values of 10, 6.9, 12, and 10 mu M, respectively. Docking studies rationalized the structure activity relationship (SAR) with the biological data. 3-Sulfo-N-benzyl-1,8-naphthalimide, potassium salt (25) with an IC50 approximate to 6.9 mu M, is the most potent clathrin terminal domain-amphiphysin inhibitor reported to date.