N-[((5S)-3-{3-fluoro-4-[2-(trimethylsilyl)ethynyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide | 398152-55-1

• 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: N-[((5S)-3-{3-fluoro-4-[2-(trimethylsilyl)ethynyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide
• CAS: 398152-55-1
• 化学式: C₁₇H₂₁FN₂O₃Si
• 分子量: 348.449
• InChiKey: MNEMBYWQCMFKRI-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.52
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  58.64
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  N-[((5S)-3-{3-fluoro-4-[2-(trimethylsilyl)ethynyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 0.75h， 以60%的产率得到N-{[(5S)-3-(4-ethynyl-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide
  参考文献：
  名称：

  Carbon–carbon-linked (pyrazolylphenyl)oxazolidinones with antibacterial activity against multiple drug resistant gram-positive and fastidious gram-negative bacteria

  摘要：

  In an effort to expand the spectrum of activity of the oxazolidinone class of antibacterial agents to include Gram-negative bacteria, a series of new carbon-carbon linked pyrazolylphenyl analogues has been prepared. The alpha -N-substituted methyl pyrazole (10 alpha) in the C3-linked series exhibited very good Gram-positive activity with MICs less than or equal to 0.5-1 mug/mL and moderate Gramnegative activity with MICs = 2-8 mug/mL against Haemophilus influence and Moraxella catarrhalis. This analogue was also found to have potent in vivo activity with an ED50 = 1.9 mg/kg. beta -Substitution at the C3-linked pyrazole generally results in a loss of activity. The C4-linked pyrazoles are slightly more potent than their counterparts in the C3-linked series. Most of the analogues in the C4-linked series exhibited similar levels of activity in vitro, but lower levels of activity in vivo than 10 alpha. In addition, incorporation of a thioamide moiety in selected C4-linked pyrazole analogues results in an enhancement of in vitro activity leading to compounds several times more potent than eperezolid. linezolid and vancomycin. The thioamide of the N-cyanomethyl pyrazole analogue (34) exhibited an exceptional in vitro activity with MICs of less than or equal to 0.06-0.25 kg/mL against Gram-positive pathogens and with MICs of 1 mug/mL against fastidious Gram-negative pathogens. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00233-4
• 作为产物：
  描述：

  (S)-N-[3-(3-氟-4-碘-苯基)-2-氧代-唑烷-5-甲基]-乙酰氨 、 三甲基乙炔基硅 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以99%的产率得到N-[((5S)-3-{3-fluoro-4-[2-(trimethylsilyl)ethynyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide
  参考文献：
  名称：

  Carbon–carbon-linked (pyrazolylphenyl)oxazolidinones with antibacterial activity against multiple drug resistant gram-positive and fastidious gram-negative bacteria

  摘要：

  In an effort to expand the spectrum of activity of the oxazolidinone class of antibacterial agents to include Gram-negative bacteria, a series of new carbon-carbon linked pyrazolylphenyl analogues has been prepared. The alpha -N-substituted methyl pyrazole (10 alpha) in the C3-linked series exhibited very good Gram-positive activity with MICs less than or equal to 0.5-1 mug/mL and moderate Gramnegative activity with MICs = 2-8 mug/mL against Haemophilus influence and Moraxella catarrhalis. This analogue was also found to have potent in vivo activity with an ED50 = 1.9 mg/kg. beta -Substitution at the C3-linked pyrazole generally results in a loss of activity. The C4-linked pyrazoles are slightly more potent than their counterparts in the C3-linked series. Most of the analogues in the C4-linked series exhibited similar levels of activity in vitro, but lower levels of activity in vivo than 10 alpha. In addition, incorporation of a thioamide moiety in selected C4-linked pyrazole analogues results in an enhancement of in vitro activity leading to compounds several times more potent than eperezolid. linezolid and vancomycin. The thioamide of the N-cyanomethyl pyrazole analogue (34) exhibited an exceptional in vitro activity with MICs of less than or equal to 0.06-0.25 kg/mL against Gram-positive pathogens and with MICs of 1 mug/mL against fastidious Gram-negative pathogens. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00233-4

文献信息

• New carbon-linked azole oxazolidinones with improved potency and pharmacokinetics
  作者：Sheila I. Hauck、Christer Cederberg、Amanda Doucette、Lena Grosser、Neil J. Hales、Grace Poon、Michael B. Gravestock

  DOI：10.1016/j.bmcl.2006.10.063

  日期：2007.1

  Substitution of phenyl oxazolidinones with carbon-linked azoles resulted in the discovery of a new class of potent oxazolidinones that have excellent Gram-positive activity. In addition, replacement of the C-5 acetamide side chains with a 4-methyl triazole diminished monoamine oxidase activity. The synthesis and biological evaluation of these compounds are reported. (c) 2006 Elsevier Ltd. All rights reserved.