(S)-2-nitro-6-(tetrahydro-pyran-2-yloxy)-6,7-dihydro-5H-imidazo[2,1-b]-[1,3]oxazine | 187235-06-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-2-nitro-6-(tetrahydro-pyran-2-yloxy)-6,7-dihydro-5H-imidazo[2,1-b]-[1,3]oxazine
• 英文别名: (6S)-2-nitro-6-(oxan-2-yloxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
• CAS: 187235-06-9
• 化学式: C₁₁H₁₅N₃O₅
• 分子量: 269.257
• InChiKey: ODYNBCFURHSFFF-PEHGTWAWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  91.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-nitro-6-(tetrahydro-pyran-2-yloxy)-6,7-dihydro-5H-imidazo[2,1-b]-[1,3]oxazine 在 盐酸 作用下， 以 甲醇 为溶剂， 以92 %的产率得到(S)-2-硝基-6,7-二氢-5H-咪唑并[2,1-b][1,3]恶嗪-6-醇
  参考文献：
  名称：

  咪唑并[2,1-b][1,3]恶嗪衍生物的合成及其对多重耐药菌株的抗结核活性

  摘要：

  应对结核病耐药性：开展了一项热门优化活动，以优化一系列先前确定的苯并呋喃酮衍生物。通过将苯并呋喃与咪唑并[2,1- b ][1,3]恶嗪亚基转换，我们发现了一系列新的先导化合物，在体外抑制 MDR-Mtb和巨噬细胞内分枝杆菌生长方面具有优异的活性。此外，新化合物没有表现出针对三种细胞系的细胞毒性或对大蜡螟的任何毒性。

  DOI：

  10.1002/cmdc.202300015
• 作为产物：
  描述：

  1-[(S)-3-(tert-butyl-dimethyl-silanyloxy)-2-(tetrahydro-pyran-2-yloxy)-propyl]-2-chloro-4-nitro-1H-imidazole 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.12h， 生成 (S)-2-nitro-6-(tetrahydro-pyran-2-yloxy)-6,7-dihydro-5H-imidazo[2,1-b]-[1,3]oxazine
  参考文献：
  名称：

  WO2007/75872

  摘要：

  公开号：

文献信息

• PA-824的合成方法
  申请人：瑞阳制药股份有限公司

  公开号：CN107915747B

  公开（公告）日：2020-11-10

  本发明涉及一种PA‑824的合成方法，属于医药化工技术领域。本发明所述的PA‑824的合成方法，是在加热条件下，利用LiOH对脂肪族硅醚保护基进行脱保护。本发明所述的PA‑824的合成方法，避免了使用四烷基氟化铵和酸性物质，操作简单便捷，提高了反应收率和目标产物的纯度，利于工业化生产。
• 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。
• Novel lead generation of an anti-tuberculosis agent active against non-replicating mycobacteria: exploring hybridization of pyrazinamide with multiple fragments
  作者：Shankar D. Markad、Parvinder Kaur、B. K. Kishore Reddy、Murugan Chinnapattu、Anandkumar Raichurkar、Radha Nandishaiah、Manoranjan Panda、Pravin S. Iyer

  DOI：10.1007/s00044-015-1352-6

  日期：2015.7

  The key to shortening tuberculosis (TB) drug regimen lies in eliminating the reservoir of non-replicating persistent (NRP) Mycobacterium tuberculosis (Mtb). Pyrazinamide (PZA) is the only known drug used as part of a combination therapy that is believed to kill NRP Mtb and achieve sterilization. PZA is active only under low pH screening conditions. Screening and identification of NRP-active anti-TB compounds are severely limited because compounds are usually inactive under regular assay conditions. In an effort to design novel NRP-active anti-TB compounds, we used pyrazinamide as a core and hybridized it with the fragments derived from marketed drugs. One of these designs, compound 8, was a hybrid with fluoroquinolone. This compound exhibited > 10 fold improvement in NRP activity under low pH condition as compared to pyrazinamide and a modest activity (0.8 log(10) kill) under nutritionally starved NRP condition. Furthermore, compound 8 was active against fluoroquinolone-resistant strains and did not show any activity in a DNA supercoiling assay (gyrase inhibition), suggesting that its mechanism of action is not that of the parent fluoroquinolone. These results provide a novel avenue in the exploration of new chemotypes that are active against non-replicating Mtb.
• NITROIMIDAZOLE COMPOUNDS
  申请人：NOVARTIS AG

  公开号：EP1984369A2

  公开（公告）日：2008-10-29
• [EN] NITROIMIDAZOLE COMPOUNDS<br/>[FR] COMPOSES DE NITROIMIDAZOLE
  申请人：NOVARTIS AG

  公开号：WO2007075872A2

  公开（公告）日：2007-07-05

  [EN] 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.
  [FR] La présente invention concerne certains composés de nitroimidazole qui possèdent des propriétés pharmaceutiques intéressantes. Ces composés sont notamment utiles dans le traitement et/ou la prévention d'infections telles que celles causées par Mycobacterium tuberculosis, Trypanosoma cruzi ou Leishmania donovani. L'invention a également trait à des compositions pharmaceutiques contenant ces composés ainsi qu'à leurs procédés de préparation.