N-(((3S,3aS)-8-fluoro-7-(1-(2-hydroxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1-oxo-3a,4-dihydro-1H,3H-benzo[b]oxazolo[3,4-d][1,4]oxazin-3-yl)methyl)cyclopropanecarboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: N-(((3S,3aS)-8-fluoro-7-(1-(2-hydroxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1-oxo-3a,4-dihydro-1H,3H-benzo[b]oxazolo[3,4-d][1,4]oxazin-3-yl)methyl)cyclopropanecarboxamide
• 英文别名: N-[[(3S,3aS)-8-fluoro-7-[1-(2-hydroxyacetyl)-3,6-dihydro-2H-pyridin-4-yl]-1-oxo-3a,4-dihydro-3H-oxazolo[4,3-c][1,4]benzoxazin-3-yl]methyl]cyclopropanecarboxamide；N-[[(3S,3aS)-8-fluoro-7-[1-(2-hydroxyacetyl)-3,6-dihydro-2H-pyridin-4-yl]-1-oxo-3a,4-dihydro-3H-[1,3]oxazolo[4,3-c][1,4]benzoxazin-3-yl]methyl]cyclopropanecarboxamide
• 化学式: C₂₂H₂₄FN₃O₆
• 分子量: 445.447
• InChiKey: ORNPLEYKNKNWCS-HKUYNNGSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (Z)-4-(5-bromo-4-fluoro-2-nitrophenoxy)-2-buten-1-ol 在 咪唑 、 盐酸 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 L-(+)-酒石酸二乙酯 、 四丁基氟化铵 、 titanium(IV)isopropoxide 、 sodium carbonate 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 甲胺 、 lithium hexamethyldisilazane 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 56.5h， 生成 N-(((3S,3aS)-8-fluoro-7-(1-(2-hydroxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl)-1-oxo-3a,4-dihydro-1H,3H-benzo[b]oxazolo[3,4-d][1,4]oxazin-3-yl)methyl)cyclopropanecarboxamide
  参考文献：
  名称：

  Discovery of Fluorine-Containing Benzoxazinyl-oxazolidinones for the Treatment of Multidrug Resistant Tuberculosis

  摘要：

  A novel series of fluorine-containing benzoxazinyl-oxazolidinones were designed and synthesized as antidrug-resistant tuberculosis agents possessing good activity and improved pharmacokinetic profiles. Compound 21 exhibited not only outstanding in vitro activity with a MIC value of 0.25-0.50 mu g/mL against drug-susceptible H(37)Rv strain and two clinically isolated drug-resistant Mycobacterium tuberculosis strains, but also acceptable in vitro ADME/T properties. Moreover, this compound displayed excellent mouse pharmacokinetic profiles with an oral bioavailability of 102% and a longer elimination half-life of 4.22 h, thereby supporting further optimization and development of this promising lead series.

  DOI：

  10.1021/acsmedchemlett.7b00068

文献信息

• Discovery of Fluorine-Containing Benzoxazinyl-oxazolidinones for the Treatment of Multidrug Resistant Tuberculosis
  作者：Hongyi Zhao、Yu Lu、Li Sheng、Zishuo Yuan、Bin Wang、Weiping Wang、Yan Li、Chen Ma、Xiaoliang Wang、Dongfeng Zhang、Haihong Huang

  DOI：10.1021/acsmedchemlett.7b00068

  日期：2017.5.11

  A novel series of fluorine-containing benzoxazinyl-oxazolidinones were designed and synthesized as antidrug-resistant tuberculosis agents possessing good activity and improved pharmacokinetic profiles. Compound 21 exhibited not only outstanding in vitro activity with a MIC value of 0.25-0.50 mu g/mL against drug-susceptible H(37)Rv strain and two clinically isolated drug-resistant Mycobacterium tuberculosis strains, but also acceptable in vitro ADME/T properties. Moreover, this compound displayed excellent mouse pharmacokinetic profiles with an oral bioavailability of 102% and a longer elimination half-life of 4.22 h, thereby supporting further optimization and development of this promising lead series.