N-{[(5S)-3-(4-ethynyl-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide | 398152-56-2

• 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-(4-ethynyl-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide
• 英文别名: N-(((5S)-3-(4-ethynyl-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl)methyl)acetamide；N-[[(5S)-3-(4-ethynyl-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide
• CAS: 398152-56-2
• 化学式: C₁₄H₁₃FN₂O₃
• 分子量: 276.267
• InChiKey: XVDNBQZIPDAJIL-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-{[(5S)-3-(4-ethynyl-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide 在 甲酸 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 N-[((5S)-3-{4-[(E)-3-(dimethylamino)-2-propenoyl]-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 在 tris-(dibenzylideneacetone)dipalladium(0) 氢氧化钾 、 copper(l) iodide 、 三(2-呋喃基)膦 、 TEA 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 N-{[(5S)-3-(4-ethynyl-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide
  参考文献：
  名称：

  New carbon-linked azole oxazolidinones with improved potency and pharmacokinetics

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2006.10.063

文献信息

• OXAZOLIDINONE CHEMOTHERAPEUTIC AGENTS
  申请人：——

  公开号：US20020045625A1

  公开（公告）日：2002-04-18

  Compounds of the formula 1 or therapeutically acceptable salts or prodrugs thereof, are useful for treating bacterial infections, psoriasis, arthritis, and toxicity due to chemotherapy. Preparation of the compounds, compositions containing the compounds, and treatment of diseases using the compounds are disclosed.

  该式化合物或其治疗上可接受的盐或前药，可用于治疗细菌感染、牛皮癣、关节炎以及化疗引起的毒性。该化合物的制备、含有该化合物的组合物以及使用该化合物治疗疾病的方法已被披露。
• Oxazolidinone chemotherapeutic agents
  申请人：Abbott Laboratories

  公开号：US06410728B1

  公开（公告）日：2002-06-25

  Compounds of the formula or therapeutically acceptable salts or prodrugs thereof, are useful for treating bacterial infections, psoriasis, arthritis, and toxicity due to chemotherapy. Preparation of the compounds, compositions containing the compounds, and treatment of diseases using the compounds are disclosed.

  该公式的化合物或其治疗上可接受的盐或前药，对于治疗细菌感染，银屑病，关节炎和化疗引起的毒性有用。公开了该化合物的制备方法，含有该化合物的组合物以及使用该化合物治疗疾病的方法。
• US6410728B1
  申请人：——

  公开号：US6410728B1

  公开（公告）日：2002-06-25
• [EN] OXAZOLIDINONE CHEMOTHERAPEUTIC AGENTS<br/>[FR] AGENTS CHIMIOTHERAPEUTIQUES D'OXAZOLIDINONE
  申请人：ABBOTT LAB

  公开号：WO2002018353A2

  公开（公告）日：2002-03-07

  Compounds of the formula (I) or therapeutically acceptable salts or prodrugs thereof, are useful for treating bacterial infections, psoriasis, arthritis, and toxicity due to chemotherapy. Preparation of the compounds, compositions containing the compounds, and treatment of diseases using the compounds are disclosed.
• 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.