(2-硝基-6,7-二氢-5H-咪唑并[2,1-B][1,3]噁嗪-7-基)甲醇 | 1263188-40-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: (2-硝基-6,7-二氢-5H-咪唑并[2,1-B][1,3]噁嗪-7-基)甲醇
• 英文名称: (2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-7-yl)methanol
• CAS: 1263188-40-4
• 化学式: C₇H₉N₃O₄
• 分子量: 199.166
• InChiKey: VMQVWUMZNJQPJV-UHFFFAOYSA-N

物化性质

• 沸点：
  438.9±41.0 °C(Predicted)
• 密度：
  1.76±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  93.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2-硝基-6,7-二氢-5H-咪唑并[2,1-B][1,3]噁嗪-7-基)甲醇 在 三苯基膦 、 偶氮二甲酸二乙酯 、 叠氮磷酸二苯酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 45.5h， 以83%的产率得到7-(azidomethyl)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
  参考文献：
  名称：

  Antileishmanial/Antitubercular 7-取代的 2-Nitroimidazooxazines 的新型接头变体提供增强的溶解度

  摘要：

  抗结核病7-取代的 2-硝基咪唑并[2,1- b ][1,3] 恶嗪先前已被证明具有有效的抗寄生虫和抗锥虫活性，最终产生了一种用于治疗内脏利什曼病的新临床研究药物 (DNDI-0690)。为了抵消开发风险，我们继续寻找具有不同候选特征的进一步线索，特别是具有更大水溶性的类似物。从一种有效的单芳基衍生物开始，首先探索了用新型胺、酰胺和脲官能团替代侧链醚键；前一种替代物在体外和体内均具有良好的耐受性但引起溶解度的微小变化（通过不太稳定的苄胺除外），而后一组导致溶解度显着提高（高达 53 倍），但抗虫效力降低至少 10 倍。最终，我们发现O-氨基甲酸酯66在内脏利什曼病小鼠模型中提供了更高的溶解度、合适的代谢稳定性、出色的口服生物利用度 (100%) 和强大的体内功效（25 mg 时寄生虫负荷减少 97% /公斤）。

  DOI：

  10.1021/acsmedchemlett.0c00649
• 作为产物：
  描述：

  (7R)-7-methyl-2-nitro-7-{[(triisopropylsilyl)oxy]methyl}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 84.0h， 以97%的产率得到(2-硝基-6,7-二氢-5H-咪唑并[2,1-B][1,3]噁嗪-7-基)甲醇
  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

文献信息

• 신규한 바이사이클릭 니트로이미다졸 카바메이트 화합물, 이를 제조하는 방법 및 이를 유효성분으로 함유하는 결핵 질환의 예방 또는 치료용 약제학적 조성물
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY 한국화학연구원(319980077651)

  公开号：KR101564425B1

  公开（公告）日：2015-10-30

  본 발명은 하기 화학식 1로 표시되는 바이사이클릭 니트로이미다졸 카바메이트 화합물, 이의 광학이성질체 또는 이의 약학적으로 허용가능한 염, 이를 제조하는 방법 및 이를 유효성분으로 함유하는 결핵 질환의 예방 또는 치료용 약제학적 조성물에 관한 것이다. [화학식 1] 상기 화학식 1에서, R1 및 R2는 각각 발명의 상세한 설명에서 정의한 바와 같다. 본 발명의 바이사이클릭 니트로이미다졸 카바메이트 화합물은 활동성 및 비활동성 결핵균에 대해 우수한 억제 효과를 나타내므로, 결핵의 치료에 유용하게 사용될 수 있다.

  本发明涉及如下化学式1所示的生物合成硝基咪唑啉酮卡巴梅特化合物、其光学异构体或其药学上可接受的盐，其制备方法及包含其作为有效成分的用于预防或治疗结核病的药物组合物。在化学式1中，R1和R2分别如发明详细说明中定义。本发明的生物合成硝基咪唑啉酮卡巴梅特化合物对活性和非活性结核菌表现出优异的抑制效果，因此可以有效地用于结核病治疗。
• NITROIMIDAZOOXAZINE AND NITROIMIDAZOOXAZOLE ANALOGUES AND THEIR USES
  申请人：Thompson Andrew Mark

  公开号：US20110028466A1

  公开（公告）日：2011-02-03

  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.

  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。
• 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。
• 바이사이클릭 니트로이미다졸 유도체 또는 이들의 광학이성질체, 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 함유하는 약제학적 조성물
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY 한국화학연구원(319980077651)

  公开号：KR101918469B1

  公开（公告）日：2018-11-15

  본 발명은 하기 화학식 1로 표시되는 바이사이클릭 니트로이미다졸 유도체 또는 이들의 광학이성질체, 이의 약학적으로 허용가능한 염, 이를 제조하는 방법 및 이를 유효성분으로 함유 하는 결핵질환 치료용 약제학적 조성물에 관한 것이다. [화학식 1]

  该发明涉及化学式1所表示的双环硝基咪唑衍生物或其光学异构体，其药学上可接受的盐，制备方法以及用作结核病治疗药物的药学组合物中的有效成分。[化学式1]
• 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。