7-(((5-bromopyridin-2-yl)oxy)methyl)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine | 1263188-42-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 7-(((5-bromopyridin-2-yl)oxy)methyl)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
• 英文别名: 7-{[(5-bromo-2-pyridinyl)oxy]methyl}-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine；7-[(5-bromopyridin-2-yl)oxymethyl]-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
• CAS: 1263188-42-6
• 化学式: C₁₂H₁₁BrN₄O₄
• 分子量: 355.148
• InChiKey: XIEBCVPLLCRNSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  95
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-(((5-bromopyridin-2-yl)oxy)methyl)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 sodium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 7-{[(5-fluoro-[2,3'-bipyridin]-6'-yl)oxy]methyl}-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
  参考文献：
  名称：

  7-Substituted 2-Nitro-5,6-dihydroimidazo[2,1-b][1,3]oxazines: Novel Antitubercular Agents Lead to a New Preclinical Candidate for Visceral Leishmaniasis

  摘要：

  Within a backup program for the clinical investigational agent pretomanid (PA-824), scaffold hopping from delamanid inspired the discovery of a novel class of potent antitubercular agents that unexpectedly possessed notable utility against the kinetoplastid disease visceral leishmaniasis (VL). Following the identification of delamanid analogue DNDI-VL-2098 as a VL preclinical candidate, this structurally related 7 substituted 2-nitro-5,6-dihydroimidazo [2,1-b][1,3]oxazine class was further explored, seeking efficacious backup compounds with improved solubility and safety. Commencing with a biphenyl lead, bioisosteres formed by replacing one phenyl by pyridine or pyrimidine showed improved solubility and potency, whereas more hydrophilic side chains reduced VL activity. In a Leishmania donovani mouse model, two racemic phenylpyridines (71 and 93) were superior, with the former providing >99% inhibition at 12.5 mg/kg (b.i.d., orally) in the Leishmania infantum hamster model. Overall, the 7R enantiomer of 71 (79) displayed more optimal efficacy, pharmacokinetics, and safety, leading to its selection as the preferred development candidate.

  DOI：

  10.1021/acs.jmedchem.7b00034
• 作为产物：
  描述：

  2-bromo-1-(but-3-en-1-yl)-4-nitro-1H-imidazole 在 咪唑 、 盐酸 、 四氧化锇 、 sodium hydride 、 N-甲基吗啉氧化物 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 59.5h， 生成 7-(((5-bromopyridin-2-yl)oxy)methyl)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
  参考文献：
  名称：

  NITROIMIDAZOOXAZINE AND NITROIMIDAZOOXAZOLE ANALOGUES AND THEIR USES

  摘要：

  当前的发明涉及硝基咪唑噁啉和硝基咪唑噁唑类似物，它们的制备方法，以及将这些化合物用作治疗结核分枝杆菌、用作抗结核药物、用作对克氏锥虫或唐氏利什曼原虫具有意外高效的抗原虫药剂，以及用于治疗其他微生物感染的用途。

  公开号：

  US20110028466A1

文献信息

• Synergistic Activity of Nitroimidazole-Oxazolidinone Conjugates against Anaerobic Bacteria
  作者：Zhijun Zhuang、Dawei Wan、Jun Ding、Shijie He、Qian Zhang、Xiaomei Wang、Ying Yuan、Yu Lu、Charles Z. Ding、Anthony Simon Lynch、Anna M. Upton、Christopher B. Cooper、William A. Denny、Zhenkun Ma

  DOI：10.3390/molecules25102431

  日期：——

  The introductions of the bicyclic 4-nitroimidazole and the oxazolidinone classes of antimicrobial agents represented the most significant advancements in the infectious disease area during the past two decades. Pretomanid, a bicyclic 4-nitroimidazole, and linezolid, an oxazolidinone, are also part of a combination regimen approved recently by the US Food and Drug Administration for the treatment of pulmonary, extensively drug resistant (XDR), treatment-intolerant or nonresponsive multidrug-resistant (MDR) Mycobacterium tuberculosis (TB). To identify new antimicrobial agents with reduced propensity for the development of resistance, a series of dual-acting nitroimidazole-oxazolidinone conjugates were designed, synthesized and evaluated for their antimicrobial activity. Compounds in this conjugate series have shown synergistic activity against a panel of anaerobic bacteria, including those responsible for serious bacterial infections.

  自行车环4-硝基咪唑和噁唑烷酮类抗微生物药物的介绍代表了过去二十年在传染病领域取得的最重要进展。Pretomanid是一种自行车环4-硝基咪唑，而利奈唑是一种噁唑烷酮，它们也是最近被美国食品药品监督管理局批准用于治疗肺部、广泛耐药（XDR）、治疗不耐受或对多药耐药（MDR）结核分枝杆菌（TB）的联合疗法的一部分。为了寻找具有减少耐药发展倾向的新抗微生物药物，设计、合成和评估了一系列双作用硝基咪唑-噁唑烷酮共轭物，以评估它们的抗微生物活性。这种共轭系列中的化合物已显示出对一系列厌氧细菌具有协同作用，包括那些导致严重细菌感染的细菌。
• Nitroimidazooxazine and nitroimidazooxazole analogues and their uses
  申请人：Global Alliance for TB Drug Development

  公开号：US08293734B2

  公开（公告）日：2012-10-23

  The current invention pertains to nitroimidazooxazine and nitroimidazooxazole analogues, their methods of preparation, and uses of the compounds as treatment for Mycobacterium tuberculosis, for use as anti-tubercular drugs, for use as anti-protozoal agents with unexpectedly high potency against Trypanosoma cruzi or Leishmania donovani, and for the treatment of other microbial infections.

  本发明涉及硝基咪唑氧噁啉和硝基咪唑氧唑类似物，其制备方法以及将这些化合物用作治疗结核分枝杆菌的药物、用作抗结核药物、用作抗原虫药物，对Trypanosoma cruzi或Leishmania donovani具有意外的高效性，并用于治疗其他微生物感染。
• NITROIMIDAZOOXAZINE ANALOGUES AND THEIR USES
  申请人：Global Alliance For Tb Drug Development

  公开号：EP2459570B1

  公开（公告）日：2014-12-24
• US8293734B2
  申请人：——

  公开号：US8293734B2

  公开（公告）日：2012-10-23