(6S)-6-({1-methyl-3-[4-(trifluoromethoxy)phenyl]-1H-pyrazol-5-yl}methoxy)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine | 1202941-72-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (6S)-6-({1-methyl-3-[4-(trifluoromethoxy)phenyl]-1H-pyrazol-5-yl}methoxy)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
• 英文别名: (6S)-({1-methyl-3-[4-(trifluoromethoxy)phenyl]-1H-pyrazol-5-yI}methoxy)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine；(6S)-6-[[2-methyl-5-[4-(trifluoromethoxy)phenyl]pyrazol-3-yl]methoxy]-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
• CAS: 1202941-72-7
• 化学式: C₁₈H₁₆F₃N₅O₅
• 分子量: 439.351
• InChiKey: XOSKCDSTRUTOKN-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  109
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  1-碘-4-(三氟甲氧基)苯 在 bis(triphenylphosphine)palladium(II) dichloride 盐酸 、 copper(l) iodide 、 三溴化磷 、 sodium hydride 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.0h， 生成 (6S)-6-({1-methyl-3-[4-(trifluoromethoxy)phenyl]-1H-pyrazol-5-yl}methoxy)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
  参考文献：
  名称：

  [EN] NITROIMIDAZOOXAZINES AND THEIR USES IN ANTI-TUBERCULAR THERAPY
  [FR] NITROIMIDAZOOXAZINES ET LEURS UTILISATIONS EN THÉRAPIE ANTITUBERCULEUSE

  摘要：

  本发明涉及新型硝基咪唑噁啉类化合物，其制备方法，以及它们作为治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用或与其他抗感染治疗方法结合使用。

  公开号：

  WO2011014774A1

文献信息

• NITROIMIDAZOOXAZINES AND THEIR USES IN ANTI-TUBERCULAR THERAPY
  申请人：Denny William Alexander

  公开号：US20120028973A1

  公开（公告）日：2012-02-02

  The present invention relates to novel nitroimidazooxazines, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

  本发明涉及新型硝基咪唑噁啉类化合物，其制备方法，以及它们作为治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用或与其他抗感染治疗联合使用。
• Synthesis and Structure−activity Relationships of Antitubercular 2-Nitroimidazooxazines Bearing Heterocyclic Side Chains
  作者：Hamish S. Sutherland、Adrian Blaser、Iveta Kmentova、Scott G. Franzblau、Baojie Wan、Yuehong Wang、Zhenkun Ma、Brian D. Palmer、William A. Denny、Andrew M. Thompson

  DOI：10.1021/jm901378u

  日期：2010.1.28

  Recently described biphenyl analogues Of the antituberculosis drug PA-824 displayed improved potencies against M. tuberculosis but were poorly soluble. Heterobiaryl analogues of these, in which the first phenyl ring was replaced with various 5-membered ring heterocycles, were prepared with the aim of identifying potent new candidates with improved aqueous solubility. The compounds were constructed by coupling the chiral 2-nitroimidazooxazine alcohol with various halomethyl-substituted arylheterocycles, by cycloadditions to a propargyl ether derivative of this alcohol, or by Suzuki couplings on haloheterocyclic methyl ether derivatives. The arylheterocyclic compounds were all more hydrophilic than their corresponding biphenyl analogues, and several showed solubility improvements. 1-Methylpyrazole, 1,3-linked-pyrazole, 2,4-linked-triazole, and tetrazole analogues had 3- to 7-fold higher MIC potencies against replicating M. tb than predicted by their lipophilicities. Two pyrazole analogues were >10-fold more efficacious than the parent drug in a mouse model of acute M. tb infection, and one displayed a 2-fold higher solubility.
• US9198913B2
  申请人：——

  公开号：US9198913B2

  公开（公告）日：2015-12-01