N-(2-(5'-nitropyridin-2'-ylamino)ethyl)phthalimide | 813468-90-5

• 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: N-(2-(5'-nitropyridin-2'-ylamino)ethyl)phthalimide
• 英文别名: 2-(2-((5-nitropyridin-2-yl)amino)ethyl)isoindoline-1,3-dione；2-[2-[(5-Nitropyridin-2-yl)amino]ethyl]isoindole-1,3-dione
• CAS: 813468-90-5
• 化学式: C₁₅H₁₂N₄O₄
• 分子量: 312.285
• InChiKey: QOEXJHBMGCEEAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(2-(5'-nitropyridin-2'-ylamino)ethyl)phthalimide 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以60%的产率得到N-(5-硝基-2-吡啶基)-1,2-乙二胺
  参考文献：
  名称：

  Synthesis and Evaluation of Bifunctional Aminothiazoles as Antiretrovirals Targeting the HIV-1 Nucleocapsid Protein

  摘要：

  Small molecule inhibitors of the HIV-1 nucleocapsid protein (NC) are considered as promising agents in the treatment of HIV/AIDS. In an effort to exploit the privileged 2-amino-4-phenylthiazole moiety in NC inhibition, here we conceived, synthesized, and tested in vitro 18 NC inhibitors (NCIs) bearing a double functionalization. In these NCIs, one part of the molecule is deputed to interact noncovalently with the NC hydrophobic pocket, while the second portion is designed to interact with the N-terminal domain of NC. This binding hypothesis was verified by molecular dynamics simulations, while the linkage between these two pharmacophores was found to enhance antiretroviral activity both on the wild-type virus and on HIV-1 strains with resistance to currently licensed drugs. The two most interesting compounds 6 and 13 showed no cytotoxicity, thus becoming valuable leads for further investigations.

  DOI：

  10.1021/acsmedchemlett.8b00506
• 作为产物：
  描述：

  [2-(1,3-二氧代-1,3-二氢-2H-异吲哚-2-基)乙基]氨基甲酸叔丁酯 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 N-(2-(5'-nitropyridin-2'-ylamino)ethyl)phthalimide
  参考文献：
  名称：

  Synthesis and Evaluation of Bifunctional Aminothiazoles as Antiretrovirals Targeting the HIV-1 Nucleocapsid Protein

  摘要：

  Small molecule inhibitors of the HIV-1 nucleocapsid protein (NC) are considered as promising agents in the treatment of HIV/AIDS. In an effort to exploit the privileged 2-amino-4-phenylthiazole moiety in NC inhibition, here we conceived, synthesized, and tested in vitro 18 NC inhibitors (NCIs) bearing a double functionalization. In these NCIs, one part of the molecule is deputed to interact noncovalently with the NC hydrophobic pocket, while the second portion is designed to interact with the N-terminal domain of NC. This binding hypothesis was verified by molecular dynamics simulations, while the linkage between these two pharmacophores was found to enhance antiretroviral activity both on the wild-type virus and on HIV-1 strains with resistance to currently licensed drugs. The two most interesting compounds 6 and 13 showed no cytotoxicity, thus becoming valuable leads for further investigations.

  DOI：

  10.1021/acsmedchemlett.8b00506

文献信息

• Kinetic versus thermodynamic access to imidazoisoindolones, benzimidazoisoindolones, and [1,4]diazepinoisoindolones: intramolecular nitrogen and π-aromatic trapping of N-acyliminium cation
  作者：Armelle Cul、Adam Daïch、Bernard Decroix、Gérard Sanz、Luc Van Hijfte

  DOI：10.1016/j.tet.2004.07.107

  日期：2004.11

  Efficient assembly of substituted imidazo[2,1-a]isoindolones I is reported from suitable alpha,beta-diamine IV (or corresponding (beta-nitroamine) and phthalic anhydride (1) in a three- or four-step sequence in good yields. The key step of this methodology is based on an intramolecular alpha-aza-amidoalkylation of the N-acyliminium species. Furthermore, when R-2 is an aromatic moiety a competing alpha-amidoalkylation took place and imidazo[2,1-a]isoindolones (or benzimidazo[2,1-a]isoindolones) I and/or isoindolo[1,4]benzodiazepines III were obtained under kinetic or thermodynamic control. The chemoselectivity of these transformations is also discussed. (C) 2004 Elsevier Ltd. All rights reserved.
• Synthesis and Evaluation of Bifunctional Aminothiazoles as Antiretrovirals Targeting the HIV-1 Nucleocapsid Protein
  作者：Mattia Mori、Maria Chiara Dasso Lang、Francesco Saladini、Nastasja Palombi、Lesia Kovalenko、Davide De Forni、Barbara Poddesu、Laura Friggeri、Alessia Giannini、Savina Malancona、Vincenzo Summa、Maurizio Zazzi、Yves Mely、Maurizio Botta

  DOI：10.1021/acsmedchemlett.8b00506

  日期：2019.4.11

  Small molecule inhibitors of the HIV-1 nucleocapsid protein (NC) are considered as promising agents in the treatment of HIV/AIDS. In an effort to exploit the privileged 2-amino-4-phenylthiazole moiety in NC inhibition, here we conceived, synthesized, and tested in vitro 18 NC inhibitors (NCIs) bearing a double functionalization. In these NCIs, one part of the molecule is deputed to interact noncovalently with the NC hydrophobic pocket, while the second portion is designed to interact with the N-terminal domain of NC. This binding hypothesis was verified by molecular dynamics simulations, while the linkage between these two pharmacophores was found to enhance antiretroviral activity both on the wild-type virus and on HIV-1 strains with resistance to currently licensed drugs. The two most interesting compounds 6 and 13 showed no cytotoxicity, thus becoming valuable leads for further investigations.