2-Bromo-1-(2-methyl-4-nitro-phenyl)-ethanone | 568556-30-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-Bromo-1-(2-methyl-4-nitro-phenyl)-ethanone
• 英文别名: Ethanone, 2-bromo-1-(2-methyl-4-nitrophenyl)-；2-bromo-1-(2-methyl-4-nitrophenyl)ethanone
• CAS: 568556-30-9
• 化学式: C₉H₈BrNO₃
• 分子量: 258.071
• InChiKey: XGTICEAUEQYQBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  62.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-Bromo-1-(2-methyl-4-nitro-phenyl)-ethanone 在 potassium phosphate 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 35.0h， 生成
  参考文献：
  名称：

  Augmenting the Activity of Macrolide Adjuvants against Acinetobacter baumannii

  摘要：

  Approximately 1.7 million Americans develop hospital associated infections each year, resulting in more than 98,000 deaths. One of the main contributors to such infections is the Gram-negative pathogen Acinetobacter baumannii. Recently, it was reported that aryl 2-aminoimidazole (2-AI) compounds potentiate macrolide antibiotics against a highly virulent strain of A. baumannii, AB5075. The two lead compounds in that report increased clarithromycin (CLR) potency against AB5075 by 16-fold, lowering the minimum inhibitory concentration (MIC) from 32 to 2 mu g/mL at a concentration of 10 mu M. Herein, we report a structure-activity relationship study of a panel of derivatives structurally inspired by the previously reported aryl 2-AI leads. Substitutions around the core phenyl ring yielded a lead that potentiates clarithromycin by 64- and 32-fold against AB5075 at 10 and 7.5 mu M, exceeding the dose response of the original lead. Additional probing of the amide linker led to the discovery of two urea containing adjuvants that suppressed clarithromycin resistance in AB5075 by 64- and 128-fold at 7.5 mu M. Finally, the originally reported adjuvant was tested for its ability to suppress the evolution of resistance to clarithromycin over the course of nine consecutive days. At 30 mu M, the parent compound reduced the CLR MIC from 512 to 2 mu g/mL, demonstrating that the original lead remained active against a more CLR resistant strain of AB5075.

  DOI：

  10.1021/acsmedchemlett.0c00276
• 作为产物：
  描述：

  2-甲基-4-硝基苯甲酸 在 4-二甲氨基吡啶 、 草酰氯 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-Bromo-1-(2-methyl-4-nitro-phenyl)-ethanone
  参考文献：
  名称：

  Augmenting the Activity of Macrolide Adjuvants against Acinetobacter baumannii

  摘要：

  Approximately 1.7 million Americans develop hospital associated infections each year, resulting in more than 98,000 deaths. One of the main contributors to such infections is the Gram-negative pathogen Acinetobacter baumannii. Recently, it was reported that aryl 2-aminoimidazole (2-AI) compounds potentiate macrolide antibiotics against a highly virulent strain of A. baumannii, AB5075. The two lead compounds in that report increased clarithromycin (CLR) potency against AB5075 by 16-fold, lowering the minimum inhibitory concentration (MIC) from 32 to 2 mu g/mL at a concentration of 10 mu M. Herein, we report a structure-activity relationship study of a panel of derivatives structurally inspired by the previously reported aryl 2-AI leads. Substitutions around the core phenyl ring yielded a lead that potentiates clarithromycin by 64- and 32-fold against AB5075 at 10 and 7.5 mu M, exceeding the dose response of the original lead. Additional probing of the amide linker led to the discovery of two urea containing adjuvants that suppressed clarithromycin resistance in AB5075 by 64- and 128-fold at 7.5 mu M. Finally, the originally reported adjuvant was tested for its ability to suppress the evolution of resistance to clarithromycin over the course of nine consecutive days. At 30 mu M, the parent compound reduced the CLR MIC from 512 to 2 mu g/mL, demonstrating that the original lead remained active against a more CLR resistant strain of AB5075.

  DOI：

  10.1021/acsmedchemlett.0c00276

文献信息

• Benzimidazole-Based Schiff Base Hybrid Scaffolds: A Promising Approach to Develop Multi-Target Drugs for Alzheimer’s Disease
  作者：Rafaqat Hussain、Shoaib Khan、Hayat Ullah、Farhan Ali、Yousaf Khan、Asma Sardar、Rashid Iqbal、Farid S. Ataya、Nasser M. El-Sabbagh、Gaber El-Saber Batiha

  DOI：10.3390/ph16091278

  日期：——

  A series of benzimidazole-based Schiff base derivatives (1–18) were synthesized and structurally elucidated through 1H NMR, 13C NMR and HREI-MS analysis. Subsequently, these synthetic derivatives were subjected to evaluation for their inhibitory capabilities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). All these derivatives showed significant inhibition against AChE with an IC50 value in the range of 123.9 ± 10.20 to 342.60 ± 10.60 µM and BuChE in the range of 131.30 ± 9.70 to 375.80 ± 12.80 µM in comparison with standard Donepezil, which has IC50 values of 243.76 ± 5.70 µM (AChE) and 276.60 ± 6.50 µM (BuChE), respectively. Compounds 3, 5 and 9 exhibited potent inhibition against both AChE and BuChE. Molecular docking studies were used to validate and establish the structure–activity relationship of the synthesized derivatives.

  通过 1H NMR、13C NMR 和 HREI-MS 分析，合成了一系列基于苯并咪唑的席夫碱衍生物（1-18）并阐明了其结构。随后，对这些合成衍生物对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）的抑制能力进行了评估。所有这些衍生物对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）都有明显的抑制作用，其 IC50 值在 123.9 ± 10.20 至 342.60 ± 10.60 µM 之间，对 BuChE 的抑制作用在 131.30 ± 9.70 至 375.80 ± 12.80 µM 之间，而标准物质多奈哌齐的 IC50 值分别为 243.76 ± 5.70 µM（AChE）和 276.60 ± 6.50 µM（BuChE）。化合物 3、5 和 9 对 AChE 和 BuChE 都有很强的抑制作用。分子对接研究用于验证和建立合成衍生物的结构-活性关系。
• Inhibitors of inosine monophosphate dehydrogenase: SARs about the N-[3-Methoxy-4-(5-oxazolyl)phenyl moiety
  作者：Edwin J. Iwanowicz、Scott H. Watterson、Junqing Guo、William J. Pitts、T.G. Murali Dhar、Zhongqi Shen、Ping Chen、Henry H. Gu、Catherine A. Fleener、Katherine A. Rouleau、Daniel L. Cheney、Robert M. Townsend、Diane L. Hollenbaugh

  DOI：10.1016/s0960-894x(03)00258-0

  日期：2003.6

  The first reported structure-activity relationships (SARs) about the N-[3-methoxy-4-(5-oxazolyi)phenyl moiety for a series of recently disclosed inosine monophosphate dehydrogenase (IMPDH) inhibitors are described. The syntheses and in vitro inhibitory values for IMPDH II, and T-cell proliferation (for select analogues) are given. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Augmenting the Activity of Macrolide Adjuvants against <i>Acinetobacter baumannii</i>
  作者：Veronica B. Hubble、Kyle R. Bartholomew、Alexander W. Weig、Sara M. Brackett、Samantha L. Barlock、Anne E. Mattingly、Ansley M. Nemeth、Roberta J. Melander、Christian Melander

  DOI：10.1021/acsmedchemlett.0c00276

  日期：2020.9.10

  Approximately 1.7 million Americans develop hospital associated infections each year, resulting in more than 98,000 deaths. One of the main contributors to such infections is the Gram-negative pathogen Acinetobacter baumannii. Recently, it was reported that aryl 2-aminoimidazole (2-AI) compounds potentiate macrolide antibiotics against a highly virulent strain of A. baumannii, AB5075. The two lead compounds in that report increased clarithromycin (CLR) potency against AB5075 by 16-fold, lowering the minimum inhibitory concentration (MIC) from 32 to 2 mu g/mL at a concentration of 10 mu M. Herein, we report a structure-activity relationship study of a panel of derivatives structurally inspired by the previously reported aryl 2-AI leads. Substitutions around the core phenyl ring yielded a lead that potentiates clarithromycin by 64- and 32-fold against AB5075 at 10 and 7.5 mu M, exceeding the dose response of the original lead. Additional probing of the amide linker led to the discovery of two urea containing adjuvants that suppressed clarithromycin resistance in AB5075 by 64- and 128-fold at 7.5 mu M. Finally, the originally reported adjuvant was tested for its ability to suppress the evolution of resistance to clarithromycin over the course of nine consecutive days. At 30 mu M, the parent compound reduced the CLR MIC from 512 to 2 mu g/mL, demonstrating that the original lead remained active against a more CLR resistant strain of AB5075.