[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propyl]carbamic acid tert-butyl ester | 115465-11-7

• 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: [3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propyl]carbamic acid tert-butyl ester
• 英文别名: 1-tert-butoxycarbonylamino-3-phthalimidopropane；tert-butyl (3-(1,3-dioxoisoindolin-2-yl)propyl)carbamate；tert-butyl N-[3-(1,3-dioxoisoindol-2-yl)propyl]carbamate
• CAS: 115465-11-7
• 化学式: C₁₆H₂₀N₂O₄
• 分子量: 304.346
• InChiKey: RRMWIRCLTIPSQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propyl]carbamic acid tert-butyl ester 在 盐酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 2.0h， 生成 N-(3-氨基丙基)苯二甲酰亚胺
  参考文献：
  名称：

  香兰素衍生物作为阿尔茨海默氏病多靶点治疗剂的合成和体外评价。

  摘要：

  合成了许多新颖的萘二甲酰亚胺和邻苯二甲酰亚胺香兰素衍生物，并在体外评价为抗氧化剂和胆碱酯酶抑制剂。使用DPPH，FRAP和ORAC分析评估抗氧化活性。与母体化合物香草醛相比，所有化合物均显示出增强的活性。他们还在Ellman分析中显示BuChE选择性。鉴定出一种铅化合物2a（2-（3-（双（4-（3-羟基-3-甲氧基苄基）氨基）丙基）-1H-苯并[de]异喹啉-1,3（2H）-二酮）并显示出较强的抗氧化剂活性（在DPPH分析中，IC 50为16.67 µM，与FRAP分析中的香兰素相比，活性提高了25倍，在ORAC分析中与9.43 TE相比）。此外，具有IC的2a表现出有效的BuChE选择性0.27 µM中的50，比相应的AChE抑制活性高约53倍。分子建模研究表明，具有较大基团的分子（如2a中所示）表现出更好的BuChE选择性。这项工作为开发基于香草醛作为潜在的AD治疗剂的多目标杂化化合物提供了有希望的基础。

  DOI：

  10.1016/j.bmcl.2020.127505
• 作为产物：
  描述：

  N-乙氧羰基邻苯二甲酰亚胺 、 N-叔丁氧羰基-1,3-丙二胺 以 四氢呋喃 为溶剂， 反应 18.0h， 以70%的产率得到[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Preparation of Diazabicyclo[4.3.0]nonene-Based Peptidomimetics

  摘要：

  Several functionalized diazabicyclo[4.3.0]nonenes and other heterocycles have been prepared as potential peptidomimetic scaffolds. A novel and efficient method has been developed for the preparation of N-substituted gamma-lactams 13. Preparation of amidine-containing 1,5-diazabicyclo[4.3.0]nonenes 43 and 44 has been achieved through Hg-mediated cyclization of the precursor N-aminopropyl-gamma-thiolactams and subsequent functional group manipulation. Bicycle 43 represents a novel scaffold for potential peptide turn mimetics, whereas 44 could potentially be employed as an alpha-helix template attached to the C-terminus of peptides. These compounds are novel additions to the current range of small-molecule constrained peptidomimetics.

  DOI：

  10.1021/jo071074x

文献信息

• 2-Arylpropionic CXC Chemokine Receptor 1 (CXCR1) Ligands as Novel Noncompetitive CXCL8 Inhibitors
  作者：Marcello Allegretti、Riccardo Bertini、Maria Candida Cesta、Cinzia Bizzarri、Rosa Di Bitondo、Vito Di Cioccio、Emanuela Galliera、Valerio Berdini、Alessandra Topai、Giuseppe Zampella、Vincenzo Russo、Nicoletta Di Bello、Giuseppe Nano、Luca Nicolini、Massimo Locati、Piercarlo Fantucci、Saverio Florio、Francesco Colotta

  DOI：10.1021/jm049082i

  日期：2005.6.1

  The CXC chemokine CXCL8/IL-8 plays a major role in the activation and recruitment of polymorphonuclear (PMN) cells at inflammatory sites. CXCL8 activates PMNs by binding the seven-transmembrane (7-TM) G-protein-coupled receptors CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2). (R)-Ketoprofen (1) was previously reported to be a potent and specific noncompetitive inhibitor of CXCL8-induced human PMNS chemotaxis. We report here molecular modeling studies showing a putative interaction site of 1 in the TM region of CXCR1. The binding model was confirmed by alanine scanning mutagenesis and photoaffinity labeling experiments. The molecular model driven medicinal chemistry optimization of 1 led to a new class of potent and specific inhibitors of CXCL8 biological activity. Among these, repertaxin (13) was selected as a clinical candidate drug for prevention of post-ischemia reperfusion injury.
• 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.
• Preparation of Diazabicyclo[4.3.0]nonene-Based Peptidomimetics
  作者：Craig A. Hutton、Paul A. Bartlett

  DOI：10.1021/jo071074x

  日期：2007.8.31

  Several functionalized diazabicyclo[4.3.0]nonenes and other heterocycles have been prepared as potential peptidomimetic scaffolds. A novel and efficient method has been developed for the preparation of N-substituted gamma-lactams 13. Preparation of amidine-containing 1,5-diazabicyclo[4.3.0]nonenes 43 and 44 has been achieved through Hg-mediated cyclization of the precursor N-aminopropyl-gamma-thiolactams and subsequent functional group manipulation. Bicycle 43 represents a novel scaffold for potential peptide turn mimetics, whereas 44 could potentially be employed as an alpha-helix template attached to the C-terminus of peptides. These compounds are novel additions to the current range of small-molecule constrained peptidomimetics.
• Synthesis and in vitro evaluation of vanillin derivatives as multi-target therapeutics for the treatment of Alzheimer’s disease
  作者：Laura Blaikie、Graeme Kay、Paul Kong Thoo Lin

  DOI：10.1016/j.bmcl.2020.127505

  日期：2020.11

  A number of novel naphthalimido and phthalimido vanillin derivatives were synthesised, and evaluated as antioxidants and cholinesterase inhibitors in vitro. Antioxidant activity was assessed using DPPH, FRAP, and ORAC assays. All compounds demonstrated enhanced activity compared to the parent compound, vanillin. They also exhibited BuChE selectivity in Ellman’s assay. A lead compound, 2a (2-(3-(bi

  合成了许多新颖的萘二甲酰亚胺和邻苯二甲酰亚胺香兰素衍生物，并在体外评价为抗氧化剂和胆碱酯酶抑制剂。使用DPPH，FRAP和ORAC分析评估抗氧化活性。与母体化合物香草醛相比，所有化合物均显示出增强的活性。他们还在Ellman分析中显示BuChE选择性。鉴定出一种铅化合物2a（2-（3-（双（4-（3-羟基-3-甲氧基苄基）氨基）丙基）-1H-苯并[de]异喹啉-1,3（2H）-二酮）并显示出较强的抗氧化剂活性（在DPPH分析中，IC 50为16.67 µM，与FRAP分析中的香兰素相比，活性提高了25倍，在ORAC分析中与9.43 TE相比）。此外，具有IC的2a表现出有效的BuChE选择性0.27 µM中的50，比相应的AChE抑制活性高约53倍。分子建模研究表明，具有较大基团的分子（如2a中所示）表现出更好的BuChE选择性。这项工作为开发基于香草醛作为潜在的AD治疗剂的多目标杂化化合物提供了有希望的基础。