(R)-(3-(4-(4-acetylpiperazin-1-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl methanesulfonate | 1123888-62-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (R)-(3-(4-(4-acetylpiperazin-1-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl methanesulfonate
• 英文别名: [(5R)-3-[4-(4-acetylpiperazin-1-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl methanesulfonate
• CAS: 1123888-62-9
• 化学式: C₁₇H₂₂FN₃O₆S
• 分子量: 415.443
• InChiKey: ZYSOCNFKCZHCTB-CQSZACIVSA-N

物化性质

• 熔点：
  153-155 °C
• 沸点：
  663.0±55.0 °C(predicted)
• 密度：
  1.407±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (R)-(3-(4-(4-acetylpiperazin-1-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl methanesulfonate 在 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 4.5h， 生成 (R)-3-(4-(4-acetyl piperazinyl)-3-fluorophenyl)-5-((hydroxyamino)methyl)-oxazolidin-2-one 2,2,2-trifluoroacetate
  参考文献：
  名称：

  Synthesis and biological evaluation of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives

  摘要：

  Research activities on the oxazolidinone antibacterial class of compounds continue to focus on developing newer derivatives with improved potency, broad-spectrum activity and safety profiles superior to linezolid. Among the safety concerns with the oxazolidinone antibacterial agents is inhibition of monoamine oxidases (MAO) resulting from their structural similarity with toloxatone, a known MAO inhibitor. Diverse substitution patterns at the C-5 position of the oxazolidinone ring have been shown to significantly affect both antibacterial activity and MAO inhibition to varying degrees. Also, the antibacterial activity of compounds containing iron-chelating functionalities, such as the hydroxamic acids, 8-hydroxyquinolines and catechols have been correlated to their ability to alter iron intake and/or metabolism. Hence a series of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives were synthesized and evaluated for their antibacterial and MAO-A and -B inhibitory activities. The compounds were devoid of significant antibacterial activity but most demonstrated moderate MAO-A and -B inhibitory activities. Computer modeling studies revealed that the lack of potent antibacterial activity was due to significant steric interaction between the hydroxamic acid N-OH oxygen atom and one of the G2540 5'-phosphate oxygen atoms at the bacterial ribosomal binding site. Therefore, the replacement of the 5-acetamidomethyl group of linezolid with the 5-(N-hydroxyacetamido)methyl group present in the hydroxamic acid oxazolidinone derivatives was concluded to be detrimental to antibacterial activity. Furthermore, the 5-(hydroxamic acid)methyl oxazolidinone derivatives were also less active as MAO-A and -B inhibitors compared with linezolid and the selective inhibitors clorgyline and pargyline. In general, the 5-(hydroxamic acid)methyl oxazolidinone derivatives demonstrated moderate but selective MAO-B inhibitory activity. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.025
• 作为产物：
  描述：

  4-(4-Boc-哌嗪-1-基)-3-氟苯胺 在 正丁基锂 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 丙酮 为溶剂， 生成 (R)-(3-(4-(4-acetylpiperazin-1-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl methanesulfonate
  参考文献：
  名称：

  Synthesis and biological evaluation of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives

  摘要：

  Research activities on the oxazolidinone antibacterial class of compounds continue to focus on developing newer derivatives with improved potency, broad-spectrum activity and safety profiles superior to linezolid. Among the safety concerns with the oxazolidinone antibacterial agents is inhibition of monoamine oxidases (MAO) resulting from their structural similarity with toloxatone, a known MAO inhibitor. Diverse substitution patterns at the C-5 position of the oxazolidinone ring have been shown to significantly affect both antibacterial activity and MAO inhibition to varying degrees. Also, the antibacterial activity of compounds containing iron-chelating functionalities, such as the hydroxamic acids, 8-hydroxyquinolines and catechols have been correlated to their ability to alter iron intake and/or metabolism. Hence a series of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives were synthesized and evaluated for their antibacterial and MAO-A and -B inhibitory activities. The compounds were devoid of significant antibacterial activity but most demonstrated moderate MAO-A and -B inhibitory activities. Computer modeling studies revealed that the lack of potent antibacterial activity was due to significant steric interaction between the hydroxamic acid N-OH oxygen atom and one of the G2540 5'-phosphate oxygen atoms at the bacterial ribosomal binding site. Therefore, the replacement of the 5-acetamidomethyl group of linezolid with the 5-(N-hydroxyacetamido)methyl group present in the hydroxamic acid oxazolidinone derivatives was concluded to be detrimental to antibacterial activity. Furthermore, the 5-(hydroxamic acid)methyl oxazolidinone derivatives were also less active as MAO-A and -B inhibitors compared with linezolid and the selective inhibitors clorgyline and pargyline. In general, the 5-(hydroxamic acid)methyl oxazolidinone derivatives demonstrated moderate but selective MAO-B inhibitory activity. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.025

文献信息

• Design and Synthesis of Novel 5-Acetylthiomethyl Oxazolidinone Analogs
  作者：Lei Chen、Jian-Wei Wang、Li Hai、Guang-Ming Wang、Yong Wu

  DOI：10.1080/00397910902756197

  日期：2010.2.26

  The oxazolidinone class of antimicrobial agents represents a promising advance in the fight against resistant Gram-positive bacterial infections. To improve antibacterial activity and expand the spectrum of activity including Gram-negative bacteria, a series of novel 5-acetylthiomethyl oxazolidinone analogs were designed and synthesized based on the structure–activity relationship studies. The structures

  恶唑烷酮类抗微生物剂代表了在对抗耐药革兰氏阳性细菌感染方面的一个有希望的进步。为了提高抗菌活性并扩大包括革兰氏阴性菌在内的抗菌谱，基于结构-活性关系研究，设计并合成了一系列新型 5-乙酰硫甲基恶唑烷酮类似物。目标化合物和主要中间体的结构经1H NMR、13C NMR、红外(IR)、质谱(MS)和元素分析确证。
• Synthesis and biological evaluation of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives
  作者：Oludotun A. Phillips、Roselyn D'Silva、Teklu O. Bahta、Leyla H. Sharaf、Edet E. Udo、Ludmil Benov、D. Eric Walters

  DOI：10.1016/j.ejmech.2015.10.025

  日期：2015.12

  Research activities on the oxazolidinone antibacterial class of compounds continue to focus on developing newer derivatives with improved potency, broad-spectrum activity and safety profiles superior to linezolid. Among the safety concerns with the oxazolidinone antibacterial agents is inhibition of monoamine oxidases (MAO) resulting from their structural similarity with toloxatone, a known MAO inhibitor. Diverse substitution patterns at the C-5 position of the oxazolidinone ring have been shown to significantly affect both antibacterial activity and MAO inhibition to varying degrees. Also, the antibacterial activity of compounds containing iron-chelating functionalities, such as the hydroxamic acids, 8-hydroxyquinolines and catechols have been correlated to their ability to alter iron intake and/or metabolism. Hence a series of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives were synthesized and evaluated for their antibacterial and MAO-A and -B inhibitory activities. The compounds were devoid of significant antibacterial activity but most demonstrated moderate MAO-A and -B inhibitory activities. Computer modeling studies revealed that the lack of potent antibacterial activity was due to significant steric interaction between the hydroxamic acid N-OH oxygen atom and one of the G2540 5'-phosphate oxygen atoms at the bacterial ribosomal binding site. Therefore, the replacement of the 5-acetamidomethyl group of linezolid with the 5-(N-hydroxyacetamido)methyl group present in the hydroxamic acid oxazolidinone derivatives was concluded to be detrimental to antibacterial activity. Furthermore, the 5-(hydroxamic acid)methyl oxazolidinone derivatives were also less active as MAO-A and -B inhibitors compared with linezolid and the selective inhibitors clorgyline and pargyline. In general, the 5-(hydroxamic acid)methyl oxazolidinone derivatives demonstrated moderate but selective MAO-B inhibitory activity. (C) 2015 Elsevier Masson SAS. All rights reserved.