[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.