2-{[(6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl]-oxy}-N-[4-(trifluoromethoxy)phenyl]acetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-{[(6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl]-oxy}-N-[4-(trifluoromethoxy)phenyl]acetamide
• 英文别名: 2-((S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yloxy)-N-(4-trifluoromethoxyphenyl)-acetamide；2-[[(6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl]oxy]-N-[4-(trifluoromethoxy)phenyl]acetamide
• 化学式: C₁₅H₁₃F₃N₄O₆
• 分子量: 402.287
• InChiKey: PEFPMDAHYPUEME-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  ((S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yloxy)-acetic acid 、 对三氟甲氧基苯胺 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 为溶剂， 反应 0.08h， 生成 2-{[(6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl]-oxy}-N-[4-(trifluoromethoxy)phenyl]acetamide
  参考文献：
  名称：

  WO2007/75872

  摘要：

  公开号：

文献信息

• Nitroimidazole Compounds
  申请人：Jiricek Jan

  公开号：US20080275035A1

  公开（公告）日：2008-11-06

  The present invention relates to certain nitroimidazole compounds, which have interesting pharmaceutical properties. In particular, the compounds are useful in the treatment and/or prevention of infections such as those caused by Mycobacterium tuberculosis, Trypanosoma cruzi or Leishmania donovani . The invention also relates to pharmaceutical compositions containing the compounds, as well as processes for their preparation.

  本发明涉及某些硝基咪唑化合物，具有有趣的药理特性。特别地，这些化合物在治疗和/或预防由结核分枝杆菌、克鲁兹锥虫或唇鞭毛虫等引起的感染方面是有用的。该发明还涉及含有这些化合物的药物组合物，以及它们的制备方法。
• Structure–Activity Relationships for Amide-, Carbamate-, And Urea-Linked Analogues of the Tuberculosis Drug (6<i>S</i>)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5<i>H</i>-imidazo[2,1-<i>b</i>][1,3]oxazine (PA-824)
  作者：Adrian Blaser、Brian D. Palmer、Hamish S. Sutherland、Iveta Kmentova、Scott G. Franzblau、Baojie Wan、Yuehong Wang、Zhenkun Ma、Andrew M. Thompson、William A. Denny

  DOI：10.1021/jm2012276

  日期：2012.1.12

  Analogues of clinical tuberculosis drug (6S)-2-nitro-6-[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824), in which the OCH2 linkage was replaced with amide, carbamate, and urea functionality, were investigated as an alternative approach to address oxidative metabolism, reduce lipophilicity, and improve aqueous solubility. Several soluble monoaryl examples displayed moderately improved (similar to 2- to 4-fold) potencies against replicating Mycobacterium tuberculosis but were generally inferior inhibitors under anaerobic (nonreplicating) conditions. More lipophilic biaryl derivatives mostly displayed similar or reduced potencies to these in contrast to the parent biaryl series. The leading biaryl carbamate demonstrated exceptional metabolic stability and a 5-fold better efficacy than the parent drug in a mouse model of acute M. tuberculosis infection but was poorly soluble. Bioisosteric replacement of this biaryl moiety by arylpiperazine resulted in a soluble, orally bioavailable carbamate analogue providing identical activity in the acute model, comparable efficacy to OPC-67683 in a chronic infection model, favorable pharmacokinetic profiles across several species, and enhanced safety.
• WO2007/75872
  申请人：——

  公开号：——

  公开（公告）日：——