2-nitro-7-{[(triisopropylsilyl)oxy]methyl}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine | 1263188-39-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-nitro-7-{[(triisopropylsilyl)oxy]methyl}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
• 英文别名: 2-nitro-7-(((triisopropylsilyl)oxy)methyl)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine；(2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-7-yl)methoxy-tri(propan-2-yl)silane
• CAS: 1263188-39-1
• 化学式: C₁₆H₂₉N₃O₄Si
• 分子量: 355.509
• InChiKey: WCAKGVNZVRTTNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.13
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-nitro-7-{[(triisopropylsilyl)oxy]methyl}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine 在 盐酸 、 氨 作用下， 以 乙醇 、 甲醇 为溶剂， 反应 35.0h， 以96%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：

  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
• 作为产物：
  描述：

  4-(2-bromo-4-nitro-1H-imidazol-1-yl)butane-1,2-diol 在 咪唑 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 18.0h， 生成 2-nitro-7-{[(triisopropylsilyl)oxy]methyl}-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

• 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。
• 7-Substituted 2-Nitro-5,6-dihydroimidazo[2,1-<i>b</i>][1,3]oxazines: Novel Antitubercular Agents Lead to a New Preclinical Candidate for Visceral Leishmaniasis
  作者：Andrew M. Thompson、Patrick D. O’Connor、Andrew J. Marshall、Vanessa Yardley、Louis Maes、Suman Gupta、Delphine Launay、Stephanie Braillard、Eric Chatelain、Scott G. Franzblau、Baojie Wan、Yuehong Wang、Zhenkun Ma、Christopher B. Cooper、William A. Denny

  DOI：10.1021/acs.jmedchem.7b00034

  日期：2017.5.25

  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.