N-[1-pyrrolidinoethyl]-3-amino-1,8-naphthalimide | 69408-83-9

• 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-[1-pyrrolidinoethyl]-3-amino-1,8-naphthalimide
• 英文别名: 3-amino-N-[2-(N-pyrrolidinyl)ethyl]-1,8-naphthalimide；NCI-308849；NSC 308849；5-Amino-2-(2-(1-pyrrolidinyl)ethyl)-1H-benzo(de)isoquinoline-1,3(2H)-dione；5-amino-2-(2-pyrrolidin-1-ylethyl)benzo[de]isoquinoline-1,3-dione
• CAS: 69408-83-9
• 化学式: C₁₈H₁₉N₃O₂
• 分子量: 309.368
• InChiKey: TXYIFVDECCPRPY-UHFFFAOYSA-N

物化性质

• 熔点：
  195-197 °C(Solv: ethanol (64-17-5))
• 沸点：
  551.4±35.0 °C(Predicted)
• 密度：
  1.331±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(1',2'-dicarbo-closo-dodecaborane-1'-yl)propanoic acid 、 N-[1-pyrrolidinoethyl]-3-amino-1,8-naphthalimide 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 以66%的产率得到N-[2-(N-pyrrolidinyl)ethyl]-3-[(1,2-dicarba-closo-dodecaborane-1-yl)propanamido]-1,8-naphthalimide
  参考文献：
  名称：

  新型3-Carboranyl-1,8-萘二甲酰亚胺衍生物作为潜在抗癌剂的设计，合成和评价

  摘要：

  我们利用点击化学，还原胺化和酰胺化反应合成了一系列新颖的3-carbananyl-1,8-naphthalimide衍生物，mitonafide和pinafide类似物，并研究了它们在体外对细胞毒性，细胞死亡，细胞周期以及细胞生成的影响。 HepG2癌细胞系中的活性氧。分析表明，带有邻-或间-碳烷的改性萘酐和萘二甲酰亚胺表现出多种活性。萘二甲酰亚胺比萘二甲酸酐更具细胞毒性，对化合物9测得的最高IC 50值（3.10 µM）。这些化合物能够在G0 / G1或G2M期诱导细胞周期停滞，并促进细胞凋亡，自噬或肥大病。最有前途的缀合物35引起强烈的细胞凋亡并诱导ROS产生，这已通过DNA中2'-deoxy-8-oxoguanosine的水平升高而得到证明。发现测试的结合物是弱拓扑异构酶II抑制剂和经典的DNA嵌入剂。化合物33，34，和36荧光染色的HepG2细胞中的溶酶体。此外，我们使用主成分分

  DOI：

  10.3390/ijms22052772
• 作为产物：
  描述：

  1,8-萘二甲酸酐 在 盐酸 、 硫酸 、 硝酸 、 tin(ll) chloride 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 N-[1-pyrrolidinoethyl]-3-amino-1,8-naphthalimide
  参考文献：
  名称：

  Design, antiviral and cytostatic properties of isoxazolidine-containing amonafide analogues

  摘要：

  A novel series of 5-arylcarbamoyl-and 5-arylmethyl-2-methylisoxazolidin-3-yl-3-phosphonates have been synthesized via cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N-substituted naphthalimide acrylamides and N-allylnaphthalimides. All cis- and trans-isoxazolidine phosphonates obtained herein were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-9d and trans-9f exhibited the highest activity (EC50 = 8.9 mu M) toward cytomegalovirus. Compounds cis-and trans-9d as well as cis- and trans-9f were found potent against HSV and Vaccinia viruses (EC50 in the 45-58 mu M range), whereas isoxazolidines 10a and 10d suppressed replication of Coxsackie B4 and Punta Toro viruses (EC(5)0 in the 45-73 mu M range). Antiproliferative evaluation of all obtained isoxazolidines revealed the promising activity of cis-9b, cis-9d, trans-9d, cis-9e, trans-9e, cis-9f and trans-9f toward tested cancer cell lines with IC50 in the 1.1-19 mu M range. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.079

文献信息

• Synthesis, photophysical and cytotoxicity evaluations of DNA targeting agents based on 3-amino-1,8-naphthalimide derived Tröger's bases
  作者：Samantha Murphy、Sandra A. Bright、Fergus E. Poynton、Thomas McCabe、Jonathan A. Kitchen、Emma B. Veale、D. Clive Williams、Thorfinnur Gunnlaugsson

  DOI：10.1039/c3ob42213e

  日期：——

  The synthesis and characterisation of five bis-1,8-naphthalimide containing Tröger's bases 1–5 formed from their corresponding 3-amino-1,8-naphthalimide precursors 6–10 is described. The photophysical investigations of 1–5 and 6–10 were carried out in several organic solvents as well as in water and as a function of pH using UV-Vis absorption and fluorescence spectroscopies. The DNA binding affinities of 1–5 in aqueous solution at pH 7.4 were also investigated using several UV-Vis absorption and fluorescence experiments by using calf thymus DNA (ct-DNA). These molecules exhibited significant DNA binding affinities; where large binding values (Kb) in the range of 106 M−1 were determined, even in competitive media (50 mM and 160 mM NaCl at pH 7.4). Thermal denaturation measurements also showed that 1–5 significantly stabilised the DNA helix. Using linear and circular dichroism we further demonstrated that the DNA binding interaction occurs both by intercalation and by groove binding. The Tröger's bases were further shown to be rapidly taken up into cells using confocal fluorescence spectroscopy; and cytotoxic studies in HeLa and MCF-7 cells showed that most of the Tröger's bases were effective cytotoxic agents with EC50 values of between 1.1–12 μM and that all the active compounds induced programmed cell death by apoptosis, where up to 70% cellular death was observed after 24 h of incubation for 4.

  描述了由相应的 3-氨基-1,8-萘二甲酰亚胺前体 6-10 形成的含有 Tröger 碱 1-5 的五种双-1,8-萘二甲酰亚胺的合成和表征。使用紫外-可见吸收和荧光光谱，在几种有机溶剂和水中进行了 1-5 和 6-10 的光物理研究，并作为 pH 的函数。还使用小牛胸腺 DNA (ct-DNA) 通过多次 UV-Vis 吸收和荧光实验研究了 1-5 在 pH 7.4 水溶液中的 DNA 结合亲和力。这些分子表现出显着的 DNA 结合亲和力；即使在竞争性介质（50 mM 和 160 mM NaCl，pH 7.4）中，也可以确定 106 M−1 范围内的大结合值 (Kb)。热变性测量还表明 1-5 显着稳定了 DNA 螺旋。使用线性和圆二色性，我们进一步证明DNA结合相互作用通过嵌入和凹槽结合发生。使用共焦荧光光谱进一步证明 Tröger 的碱基可以快速被细胞吸收； HeLa 和 MCF-7 细胞中的细胞毒性研究表明，大多数 Tröger 碱都是有效的细胞毒性剂，EC50 值在 1.1–12 μM 之间，并且所有活性化合物均通过细胞凋亡诱导程序性细胞死亡，其中高达 70% 的细胞死亡4.培养24小时后观察。
• Fernandez Brana; Martinez Sanz; Castellano, European Journal of Medicinal Chemistry, 1981, vol. 16, # 3, p. 207 - 212
  作者：Fernandez Brana、Martinez Sanz、Castellano、et al.

  DOI：——

  日期：——
• BRANA M. F.; SANZ A. M.; CASTELLANO J. M.; ROLDAN C. M.; ROLDAN C., EUR. J. MED. CHEM.-CHIM. THER., 1981, 16, NO 3, 207-212,
  作者：BRANA M. F.、 SANZ A. M.、 CASTELLANO J. M.、 ROLDAN C. M.、 ROLDAN C.

  DOI：——

  日期：——
• Design, antiviral and cytostatic properties of isoxazolidine-containing amonafide analogues
  作者：Kamil Kokosza、Graciela Andrei、Dominique Schols、Robert Snoeck、Dorota G. Piotrowska

  DOI：10.1016/j.bmc.2015.04.079

  日期：2015.7

  A novel series of 5-arylcarbamoyl-and 5-arylmethyl-2-methylisoxazolidin-3-yl-3-phosphonates have been synthesized via cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N-substituted naphthalimide acrylamides and N-allylnaphthalimides. All cis- and trans-isoxazolidine phosphonates obtained herein were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-9d and trans-9f exhibited the highest activity (EC50 = 8.9 mu M) toward cytomegalovirus. Compounds cis-and trans-9d as well as cis- and trans-9f were found potent against HSV and Vaccinia viruses (EC50 in the 45-58 mu M range), whereas isoxazolidines 10a and 10d suppressed replication of Coxsackie B4 and Punta Toro viruses (EC(5)0 in the 45-73 mu M range). Antiproliferative evaluation of all obtained isoxazolidines revealed the promising activity of cis-9b, cis-9d, trans-9d, cis-9e, trans-9e, cis-9f and trans-9f toward tested cancer cell lines with IC50 in the 1.1-19 mu M range. (C) 2015 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Evaluation of Novel 3-Carboranyl-1,8-Naphthalimide Derivatives as Potential Anticancer Agents
  作者：Sebastian Rykowski、Dorota Gurda-Woźna、Marta Orlicka-Płocka、Agnieszka Fedoruk-Wyszomirska、Małgorzata Giel-Pietraszuk、Eliza Wyszko、Aleksandra Kowalczyk、Paweł Stączek、Andrzej Bak、Agnieszka Kiliszek、Wojciech Rypniewski、Agnieszka B. Olejniczak

  DOI：10.3390/ijms22052772

  日期：——

  We synthesized a series of novel 3-carboranyl-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, using click chemistry, reductive amination and amidation reactions and investigated their in vitro effects on cytotoxicity, cell death, cell cycle, and the production of reactive oxygen species in a HepG2 cancer cell line. The analyses showed that modified naphthalic anhydrides and naphthalimides

  我们利用点击化学，还原胺化和酰胺化反应合成了一系列新颖的3-carbananyl-1,8-naphthalimide衍生物，mitonafide和pinafide类似物，并研究了它们在体外对细胞毒性，细胞死亡，细胞周期以及细胞生成的影响。 HepG2癌细胞系中的活性氧。分析表明，带有邻-或间-碳烷的改性萘酐和萘二甲酰亚胺表现出多种活性。萘二甲酰亚胺比萘二甲酸酐更具细胞毒性，对化合物9测得的最高IC 50值（3.10 µM）。这些化合物能够在G0 / G1或G2M期诱导细胞周期停滞，并促进细胞凋亡，自噬或肥大病。最有前途的缀合物35引起强烈的细胞凋亡并诱导ROS产生，这已通过DNA中2'-deoxy-8-oxoguanosine的水平升高而得到证明。发现测试的结合物是弱拓扑异构酶II抑制剂和经典的DNA嵌入剂。化合物33，34，和36荧光染色的HepG2细胞中的溶酶体。此外，我们使用主成分分