N-[[(5S)-3-[4-[1-(2-cyanoethyl)pyrazol-3-yl]-3-fluoro-phenyl]-2-oxo-oxazolidin-5-yl]methyl]acetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-[[(5S)-3-[4-[1-(2-cyanoethyl)pyrazol-3-yl]-3-fluoro-phenyl]-2-oxo-oxazolidin-5-yl]methyl]acetamide
• 英文别名: N-[[(5S)-3-[4-[1-(2-cyanoethyl)pyrazol-3-yl]-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide
• 化学式: C₁₈H₁₈FN₅O₃
• 分子量: 371.371
• InChiKey: HSXMZBMRJYDZGX-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 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 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 甲酸 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.5h， 生成 N-[[(5S)-3-[4-[1-(2-cyanoethyl)pyrazol-3-yl]-3-fluoro-phenyl]-2-oxo-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

• Carbon–carbon-linked (pyrazolylphenyl)oxazolidinones with antibacterial activity against multiple drug resistant gram-positive and fastidious gram-negative bacteria
  作者：Chi Sing Lee、Debra A Allwine、Michael R Barbachyn、Kevin C Grega、Lester A Dolak、Charles W Ford、Randy M Jensen、Eric P Seest、Judith C Hamel、Ronda D Schaadt、Douglas Stapert、Betty H Yagi、Gary E Zurenko、Michael J Genin

  DOI：10.1016/s0968-0896(01)00233-4

  日期：2001.12

  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.