7-azido-1-bromoheptan-2-one | 1279724-14-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 7-azido-1-bromoheptan-2-one
• 英文别名: 7-Azido-1-bromoheptan-2-one
• CAS: 1279724-14-9
• 化学式: C₇H₁₂BrN₃O
• 分子量: 234.096
• InChiKey: XBSRJRGQXPFFLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  12
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  31.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-azido-1-bromoheptan-2-one 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl 2-amino-4-(5-aminopentyl)-1H-imidazole-1-carboxylate
  参考文献：
  名称：

  Using Small-Molecule Adjuvants to Repurpose Azithromycin for Use against Pseudomonas aeruginosa

  摘要：

  A major contributor to fatalities in cystic fibrosis (CF) patients stems from infection with opportunistic bacterium Pseudomonas aeruginosa. As a result of the CF patient's vulnerability to bacterial infections, one of the main treatment focuses is antibiotic therapy. However, the highly adaptive nature of P. aeruginosa, in addition to the intrinsic resistance to many antibiotics exhibited by most Gram-negative bacteria, means that multi-drug-resistant (MDR) strains are increasingly prevalent. This makes the eradication of pseudomonal lung infections nearly impossible once the infection becomes chronic. New methods to treat pseudomonal infections are greatly needed in order to eradicate MDR bacteria found within the respiratory tract, and ultimately better the quality of life for CF patients. Herein, we describe a novel approach to combatting pseudomonal infections through the use of bis-2-aminoimidazole adjuvants that can potentiate the activity of a macrolide antibiotic commonly prescribed to CF patients as an anti-inflammatory agent. Our lead bis-2-AI exhibits a 1024-fold reduction in the minimum inhibitory concentration of azithromycin in vitro and displays activity in a Galleria mellonella model of infection.

  DOI：

  10.1021/acsinfecdis.8b00288
• 作为产物：
  描述：

  6-溴己酸 在 sodium azide 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.75h， 生成 7-azido-1-bromoheptan-2-one
  参考文献：
  名称：

  抑制细菌对β-内酰胺的4,5-二取代的2-氨基咪唑基生物膜调节剂的结构研究

  摘要：

  已成功组装了4,5-二取代的2-氨基咪唑三唑酰胺（2-AITA）共轭物的文库。经过生物筛选后，此类小分子被发现是通过抗微生物的抗甲氧西林金黄色葡萄球菌（MRSA）和耐多药鲍曼不动杆菌的增强的生物膜调节剂。（MDRAB），其活性浓度在低微摩尔范围内。该文库还接受了针对MRSA的β-内酰胺类抗生素的协同作用和重新敏化研究。通过与奥沙西林（一种对青霉素酶有抗药性的β-内酰胺抗生素）协同作用，可以抑制MRSA的抗生素抗药性。对母体2-AITA化合物进行的进一步的结构-活性关系（SAR）研究提供了2-氨基咪唑二酰胺（2-AIDA）结合物，与奥沙西林对MRSA的协同活性显着增强，从而降低了β-内酰胺抗生素的MIC值。 64倍。抗生物膜活性的提高并不一定会导致对抗生素耐药性的抑制作用增强，这表明生物膜抑制和再敏化很可能是通过不同的机制发生的。

  DOI：

  10.1002/cmdc.201200350

文献信息

• Synthesis and biological evaluation of 2-aminoimidazole/carbamate hybrid anti-biofilm and anti-microbial agents
  作者：Steven A. Rogers、Erick A. Lindsey、Daniel C. Whitehead、Trey Mullikin、Christian Melander

  DOI：10.1016/j.bmcl.2010.12.057

  日期：2011.2

  The successful marriage of structural features from our 2-aminoimidazole and menthyl carbamate classes of anti-biofilm agents has resulted in the development of a novel hybrid scaffold of biofilm modulators. The compounds were evaluated against a panel of four bacterial strains for anti-biofilm and anti-microbial activity. (C) 2010 Elsevier Ltd. All rights reserved.
• Structural Studies on 4,5-Disubstituted 2-Aminoimidazole-Based Biofilm Modulators that Suppress Bacterial Resistance to β-Lactams
  作者：Zhaoming Su、Andrew A. Yeagley、Rui Su、Lingling Peng、Christian Melander

  DOI：10.1002/cmdc.201200350

  日期：2012.11

  synergism and resensitization studies with β‐lactam antibiotics against MRSA. Lead compounds were identified that suppress the antibiotic resistance of MRSA by working synergistically with oxacillin, a β‐lactam antibiotic resistant to penicillinase. A further structure–activity relationship (SAR) study on the parent 2‐AITA compound delivered a 2‐aminoimidazole diamide (2‐AIDA) conjugate with significantly

  已成功组装了4,5-二取代的2-氨基咪唑三唑酰胺（2-AITA）共轭物的文库。经过生物筛选后，此类小分子被发现是通过抗微生物的抗甲氧西林金黄色葡萄球菌（MRSA）和耐多药鲍曼不动杆菌的增强的生物膜调节剂。（MDRAB），其活性浓度在低微摩尔范围内。该文库还接受了针对MRSA的β-内酰胺类抗生素的协同作用和重新敏化研究。通过与奥沙西林（一种对青霉素酶有抗药性的β-内酰胺抗生素）协同作用，可以抑制MRSA的抗生素抗药性。对母体2-AITA化合物进行的进一步的结构-活性关系（SAR）研究提供了2-氨基咪唑二酰胺（2-AIDA）结合物，与奥沙西林对MRSA的协同活性显着增强，从而降低了β-内酰胺抗生素的MIC值。 64倍。抗生物膜活性的提高并不一定会导致对抗生素耐药性的抑制作用增强，这表明生物膜抑制和再敏化很可能是通过不同的机制发生的。
• Using Small-Molecule Adjuvants to Repurpose Azithromycin for Use against <i>Pseudomonas aeruginosa</i>
  作者：Veronica B. Hubble、Brittany A. Hubbard、Bradley M. Minrovic、Roberta J. Melander、Christian Melander

  DOI：10.1021/acsinfecdis.8b00288

  日期：2019.1.11

  A major contributor to fatalities in cystic fibrosis (CF) patients stems from infection with opportunistic bacterium Pseudomonas aeruginosa. As a result of the CF patient's vulnerability to bacterial infections, one of the main treatment focuses is antibiotic therapy. However, the highly adaptive nature of P. aeruginosa, in addition to the intrinsic resistance to many antibiotics exhibited by most Gram-negative bacteria, means that multi-drug-resistant (MDR) strains are increasingly prevalent. This makes the eradication of pseudomonal lung infections nearly impossible once the infection becomes chronic. New methods to treat pseudomonal infections are greatly needed in order to eradicate MDR bacteria found within the respiratory tract, and ultimately better the quality of life for CF patients. Herein, we describe a novel approach to combatting pseudomonal infections through the use of bis-2-aminoimidazole adjuvants that can potentiate the activity of a macrolide antibiotic commonly prescribed to CF patients as an anti-inflammatory agent. Our lead bis-2-AI exhibits a 1024-fold reduction in the minimum inhibitory concentration of azithromycin in vitro and displays activity in a Galleria mellonella model of infection.