2-((4-nitrophenoxy)methyl)isoindoline-1,3-dione | 134697-10-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-((4-nitrophenoxy)methyl)isoindoline-1,3-dione
• 英文别名: 2-({4-nitrophenoxy}methyl)-1H-isoindole-1,3(2H)-dione；2-[(4-nitrophenoxy)methyl]isoindole-1,3-dione
• CAS: 134697-10-2
• 化学式: C₁₅H₁₀N₂O₅
• 分子量: 298.255
• InChiKey: VFFGKLUVLYIDHI-UHFFFAOYSA-N

物化性质

• 熔点：
  160-161 °C(Solv: acetone (67-64-1))
• 沸点：
  510.9±30.0 °C(Predicted)
• 密度：
  1.462±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  92.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-((4-nitrophenoxy)methyl)isoindoline-1,3-dione 在 盐酸 、 铁粉 、 氯化铵 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 正丁醇 为溶剂， 反应 78.0h， 生成 N-{3-{4-{{4-[(1,3-dioxoisoindolin-2-yl)methoxy]phenyl}amino}-7H-pyrrolo[2,3-d]pyrimidin-5-yl}phenyl}acrylamide
  参考文献：
  名称：

  用共价抑制剂靶向Her2-insYVMA-一种集中的化合物筛选和基于结构的设计方法。

  摘要：

  突变或扩增的Her2充当非小细胞肺癌的驱动因子，或介导抵抗小分子抑制剂对其家族成员表皮生长因子受体的抑制作用。迄今为止，缺乏可用于临床常规的靶向Her2的小分子抑制剂，因此，进行了新型抑制剂的开发。在这项研究中，完善的吡咯并嘧啶支架被结构化主题修饰，该结构主题来自对1600多种化合物的筛选活动，这些化合物被应用于野生型Her2及其突变体Her2-A775_G776insYVMA。设计所得的抑制剂以在Her2的结合位点共价靶向反应性半胱氨酸，并通过利用一组获得的复杂晶体结构的基于结构的药物设计进一步优化。

  DOI：

  10.1021/acs.jmedchem.0c00870
• 作为产物：
  描述：

  N-羟甲基邻苯二甲酰亚胺 在 五氯化磷 、 potassium carbonate 、 sodium iodide 作用下， 以 乙醚 、 丙酮 为溶剂， 反应 48.0h， 生成 2-((4-nitrophenoxy)methyl)isoindoline-1,3-dione
  参考文献：
  名称：

  Mechanism of hydrolysis of O-imidomethyl derivatives of phenols

  摘要：

  Three series of O-imidomethyl derivatives of para-substituted phenolic compounds were synthesized and their rates of hydrolysis were studied. Saccharin, phthalimide, and succinimide served as the imide portions of the derivatives. Their rates of hydrolysis were found to be first order with respect to hydroxide from pH 7.0 to 10 or 11 and dependent on the acidity (leaving group potential) of both the imide and the phenol portions. The more acidic the imide or the phenol, the faster the rate of hydrolysis. However, the rates of hydrolysis were more sensitive to the acidity of the phenol. Trapping experiments with cyanide also suggested that the phenol anion was functioning as the leaving group in what is apparently an S(N)2 reaction. An amide derivative was found to hydrolyze more slowly than predicted from the analogous imide series and the pK(a) of the amide. This result is apparently due partially to stereoelectronic constraints in the imide series that cause the CH2-O bond to be oriented more nearly perpendicular to the plane of the C (=O)N group and hence more accessible to nucleophilic attack.

  DOI：

  10.1021/jo00070a029

文献信息

• Synthesis and evaluation of a large library of nitroxoline derivatives as pancreatic cancer antiproliferative agents
  作者：Serena Veschi、Simone Carradori、Laura De Lellis、Rosalba Florio、Davide Brocco、Daniela Secci、Paolo Guglielmi、Mattia Spano、Anatoly P. Sobolev、Alessandro Cama

  DOI：10.1080/14756366.2020.1780228

  日期：2020.1.1

  compound. The new derivatives showed a valuable anti-proliferative effect and some displayed a greater effect as compared to nitroxoline against three pancreatic cancer cell lines with different genetic profiles. In particular, in silico pharmacokinetic data, clonogenicity assays and selectivity indexes of the most promising compounds showed several advantages for such derivatives, as compared to nitroxoline

  摘要 胰腺癌（PC）是最致命的癌症之一，在大多数情况下，被诊断为局部晚期或转移性疾病，当前的治疗选择非常不令人满意。基于旧的尿液抗菌剂硝恶啉显示的抗增殖作用，我们探索了一个新合成的大型文库，以阐明母体化合物的OH部分和吡啶环的重要性。新的衍生物显示出有价值的抗增殖作用，并且与硝基氧代林相比，对三种具有不同遗传特征的胰腺癌细胞系显示出更大的作用。特别是计算机与硝氧索林相比，最有前途的化合物的药代动力学数据，克隆形成性测定和选择性指数显示了此类衍生物的多项优势。而且，与厄洛替尼（一种批准用于PC治疗的靶向药物）相比，其中一些新型化合物对PC细胞的细胞活力和/或克隆形成能力具有更强的影响。
• Synthesis of soft alkyl phenolic ether prodrugs using Mitsunobu chemistry
  作者：Susruta Majumdar、Juha Juntunen、Sashi Sivendran、Neelam Bharti、K.B. Sloan

  DOI：10.1016/j.tetlet.2006.09.162

  日期：2006.12

  The synthesis of soft alkyl phenolic ether prodrugs in excellent yields has been reported by coupling a phenol with a hydroxymethylimide using Mitsunobu chemistry. The imides used in this study include saccharin, phthalimide, succinimide and two other compounds containing acidic imide-like N–H groups, benzotriazole, and imidazole.

  已经报道了通过使用Mitsunobu化学方法将苯酚与羟甲基酰亚胺偶联以高产率合成软烷基苯酚醚前药。本研究中使用的酰亚胺包括糖精，邻苯二甲酰亚胺，琥珀酰亚胺和另外两种含有酸性酰亚胺样N–H基团的化合物，苯并三唑和咪唑。
• Imido methyl blocked photographic dyes and dye releasing compounds
  申请人：Eastman Kodak Company

  公开号：US04363865A1

  公开（公告）日：1982-12-14

  Imidomethyl blocked photographic image dyes and dye releasing compounds are useful in photographic elements, film units and processes. The blocked photographic dyes and dye releasing compounds have the structures: ##STR1## wherein: J represents ##STR2## X represents the atoms to complete at least one 5- or 6-membered ring; R represents hydrogen, alkyl of 1 to 4 carbon atoms or aryl of 6 to 12 carbon atoms; Q represents ##STR3## --Q--DYE represents the residue of a diffusible photographic dye; and CAR is a ballasted carrier moiety from which the dye moiety is released as a function of silver halide development.

  Imidomethyl阻断的感光染料和染料释放化合物在摄影元素、胶片和工艺中非常有用。阻断的感光染料和染料释放化合物的结构如下：##STR1## 其中：J代表##STR2## X代表原子，用于完成至少一个5-或6-成员环；R代表氢、1至4个碳原子的烷基或6至12个碳原子的芳基；Q代表##STR3## --Q--DYE代表可扩散的感光染料的残基；CAR是一个带有配基的载体基团，染料基团会在银卤化物显影的作用下释放出来。
• Bratulescu, George, Revue Roumaine de Chimie, 1999, vol. 44, # 3, p. 261 - 264
  作者：Bratulescu, George

  DOI：——

  日期：——
• US5001115A
  申请人：——

  公开号：US5001115A

  公开（公告）日：1991-03-19