N-benzyl-2-bromo-N-ethylacetamide | 180513-01-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-benzyl-2-bromo-N-ethylacetamide
• CAS: 180513-01-3
• 化学式: C₁₁H₁₄BrNO
• mdl: MFCD02974375
• 分子量: 256.142
• InChiKey: KXGJYOPQSRVUNC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-benzyl-2-bromo-N-ethylacetamide 在 dirhodium tetraacetate 4-乙酰氨基苯磺酰叠氮 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 13.5h， 生成
  参考文献：
  名称：

  在Rh（II）催化的α-重氮-α-（苯磺酰基）乙酰胺的分子内CH插入中的区域和立体控制元件。

  摘要：

  [反应：请参见文字]。α-重氮-α-（苯磺酰基）乙酰胺的分子内CH插入反应具有较高的区域选择性和立体选择性，从而主要或专门提供高度官能化的γ-内酰胺。高区域选择性归因于苯基磺酰基部分的使用，该部分改变了类胡萝卜素中心的电子密度并在插入反应过程中产生了空间效应。本文还描述了确定区域选择性的三个控制元素，它们是酰胺构象，立体电子和取代基效应。

  DOI：

  10.1021/ol016647l
• 作为产物：
  描述：

  N-乙基苄胺 、 溴乙酰溴 在 TEA 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-benzyl-2-bromo-N-ethylacetamide
  参考文献：
  名称：

  在Rh（II）催化的α-重氮-α-（苯磺酰基）乙酰胺的分子内CH插入中的区域和立体控制元件。

  摘要：

  [反应：请参见文字]。α-重氮-α-（苯磺酰基）乙酰胺的分子内CH插入反应具有较高的区域选择性和立体选择性，从而主要或专门提供高度官能化的γ-内酰胺。高区域选择性归因于苯基磺酰基部分的使用，该部分改变了类胡萝卜素中心的电子密度并在插入反应过程中产生了空间效应。本文还描述了确定区域选择性的三个控制元素，它们是酰胺构象，立体电子和取代基效应。

  DOI：

  10.1021/ol016647l

文献信息

• Tricyclic heterocycles display diverse sensitivity to the A147T TSPO polymorphism
  作者：Renee Sokias、Eryn L. Werry、Hei Wun Alison Cheng、James H. Lloyd、Greta Sohler、Jonathan J. Danon、Andrew P. Montgomery、Jonathan J. Du、Quanqing Gao、David E. Hibbs、Lars M. Ittner、Tristan A. Reekie、Michael Kassiou

  DOI：10.1016/j.ejmech.2020.112725

  日期：2020.12

  The 18 kDa translocator protein (TSPO) is a target for the development of imaging agents to detect neuroinflammation. The clinical utility of second-generation TSPO ligands has been hindered by the presence of a polymorphism, rs6971, which causes a non-conservative substitution of alanine for threonine at amino acid residue 147 (TSPO A147T). Given the complex nature of TSPO binding, and the lack of

  18 kDa转运蛋白（TSPO）是开发用于检测神经炎症的成像剂的目标。rs6971多态性的存在已阻碍了第二代TSPO配体的临床应用，该多态性导致在氨基酸残基147（TSPO A147T）上丙氨酸被苏氨酸非保守取代。鉴于TSPO结合的复杂性，以及野生型和A147T形式的TSPO都缺乏非歧视性的高亲和力配体，因此开发了一系列包含各种杂环骨架的新型TSPO配体，以探索药理学驱动力在TSPO A147T。通常，N-苄基-N-甲基取代的酰胺配体对TSPO A147T的亲和力增强，含有该基序的吡唑并嘧啶乙酰胺对两种TSPO形式均表现出较低的纳摩尔结合亲和力。
• Determination and reduction of translocator protein (TSPO) ligand rs6971 discrimination
  作者：Renee Sokias、Eryn L. Werry、Sook W. Chua、Tristan A. Reekie、Lenka Munoz、Erick C. N. Wong、Lars M. Ittner、Michael Kassiou

  DOI：10.1039/c6md00523c

  日期：——

  The 18 kDa translocator protein (TSPO) is a target for development of diagnostic imaging agents for glioblastoma and neuroinflammation. Clinical translation of TSPO imaging agents has been hindered by the presence of a polymorphism, rs6971, which causes a non-conservative substitution of alanine for threonine at amino acid residue 147 (TSPO A147T). Disclosed brain-permeant second-generation TSPO ligands

  18 kDa转运蛋白（TSPO）是胶质母细胞瘤和神经炎症诊断成像剂开发的目标。rs6971多态性的存在已阻碍了TSPO成像剂的临床翻译，该多态性导致在氨基酸残基147（TSPO A147T）上将苏氨酸非保守性替换为丙氨酸。与野生型蛋白（TSPO WT）相比，公开的脑渗透性第二代TSPO配体以降低的亲和力与TSPO A147T结合。由于缺乏关于配体结构如何差异影响与两种形式的TSPO相互作用的知识，阻碍了开发以类似的高亲和力结合TSPO WT和TSPO A147T的TSPO配体的努力。为了获得真知灼见，我们建立了稳定表达人类TSPO WT和TSPO A147T的人类胚胎肾细胞系，N-烷基化咔唑支架影响对两种TSPO同工型的亲和力。这项研究开发的大多数新类似物对TSPO WT的亲和力都很高，而对TSPO A147T的亲和力则低5-6倍。吸电子取代基的加入产生了对TSPO A147T具有最高亲和力但不降低对TSPO
• Synthesis and Structure–Activity Relationship Studies in Translocator Protein Ligands Based on a Pyrazolo[3,4-<i>b</i>]quinoline Scaffold
  作者：Andrea Cappelli、Giulia Bini、Salvatore Valenti、Germano Giuliani、Marco Paolino、Maurizio Anzini、Salvatore Vomero、Gianluca Giorgi、Antonio Giordani、Luigi Piero Stasi、Francesco Makovec、Carla Ghelardini、Lorenzo Di Cesare Mannelli、Alessandra Concas、Patrizia Porcu、Giovanni Biggio

  DOI：10.1021/jm200770f

  日期：2011.10.27

  As a further development of our large program focused on the medicinal chemistry of translocator protein [TSPO (18 kDa)] ligands, a new class of compounds related to alpidem has been designed using SSR180575, emapunil, and previously published pyrrolo[3,4-b]quinoline derivatives 9 as templates. The designed compounds were synthesized by alkylation of the easily accessible 4-methyl-2-phenyl-1H-pyrazolo[3,4-b]quinolin-3(2H)-one derivatives 13-15 with the required bromoacetamides. Along with the expected 2-(4-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazolo[3,4-b]quinolin-1-yl)acetamide derivatives 10, 2-(4-methyl-3-oxo-2-phenyl-2H-pyrazolo[3,4-b]quinolin-9(3H)-yl)acetamide isomers 11 were isolated and characterized. The high TSPO affinity shown by new pyrazolo[3,4-b]quinoline derivatives 10 and especially 11 leads the way to further expand the chemical diversity in TSPO ligands and provides new templates and structure affinity relationship data potentially useful in the design of new anxiolytic and neuroprotective agents.
• Discovery of thienopyrrolotriazine derivatives to protect mitochondrial function against Aβ-induced neurotoxicity
  作者：TaeHun Kim、Woo Seung Son、Mohammad Neaz Morshed、Ashwini M. Londhe、Seo Yun Jung、Jong-Hyun Park、Woo-Kyu Park、Sang Min Lim、Ki Duk Park、Sung Jin Cho、Kyu-Sung Jeong、Jiyoun Lee、Ae Nim Pae

  DOI：10.1016/j.ejmech.2017.09.033

  日期：2017.12

  Recovery of mitochondrial dysfunction has gained increasing attention as an alternative therapeutic strategy for Alzheimer's disease (AD). Recent studies suggested that the 18 kDa mitochondrial translocator protein (TSPO) has the potential to serve as a drug target for the treatment of AD. In this study, we generated a structure-based pharmacophore model and virtually screened a commercial library, identifying SVH07 as a virtual hit, which contained a tricyclic core structure, thieno[2',3':4,5]pyrrolo[1,2-d] [1,2,4]triazine group. A series of SVH07 analogues were synthesized and their effects on the mitochondrial membrane potential and ATP production were determined by using neuronal cells under A beta-induced toxicity. Among these analogues, compound 26 significantly recovered mitochondrial membrane depolarization and ATP production. In vitro binding assays indicated that SVH07 and 26 showed high affinities to TSPO with the IC50 values in a nanomolar range. We believe that compound 26 is a promising lead compound for the development of TSPO-targeted mitochondrial functional modulators with therapeutic potential in AD. (C) 2017 Elsevier Masson SAS. All rights reserved.
• The translocator protein ligands as mitochondrial functional modulators for the potential anti-Alzheimer agents
  作者：TaeHun Kim、Mohammad N. Morshed、Ashwini M. Londhe、Ji W. Lim、Ha E. Lee、Suengmok Cho、Sung J. Cho、Hayoung Hwang、Sang M. Lim、Jae Y. Lee、Jiyoun Lee、Ae N. Pae

  DOI：10.1080/14756366.2021.1900158

  日期：2021.1.1

  Small molecule modulators of mitochondrial function have been attracted much attention in recent years due to their potential therapeutic applications for neurodegenerative diseases. The mitochondrial translocator protein (TSPO) is a promising target for such compounds, given its involvement in the formation of the mitochondrial permeability transition pore in response to mitochondrial stress. In this study, we performed a ligand-based pharmacophore design and virtual screening, and identified a potent hit compound, 7 (VH34) as a TSPO ligand. After validating its biological activity against amyloid-β (Aβ) induced mitochondrial dysfunction and in acute and transgenic Alzheimer's disease (AD) model mice, we developed a library of analogs, and we found two most active compounds, 31 and 44, which restored the mitochondrial membrane potential, ATP production, and cell viability under Aβ-induced mitochondrial toxicity. These compounds recovered learning and memory function in acute AD model mice with improved pharmacokinetic properties.