(R)-3-(4-(2-(2-methyl-[1,3,4]oxadiazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-(methanesulfonyloxymethyl)oxazolidin-2-one | 1293990-13-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (R)-3-(4-(2-(2-methyl-[1,3,4]oxadiazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-(methanesulfonyloxymethyl)oxazolidin-2-one
• 英文别名: [(5R)-3-[3-fluoro-4-[6-(5-methyl-1,3,4-oxadiazol-2-yl)pyridin-3-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl methanesulfonate
• CAS: 1293990-13-2
• 化学式: C₁₉H₁₇FN₄O₆S
• 分子量: 448.432
• InChiKey: MUAFTBLHOHQEOV-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  133
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1H-1,2,3-三氮唑 、 (R)-3-(4-(2-(2-methyl-[1,3,4]oxadiazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-(methanesulfonyloxymethyl)oxazolidin-2-one 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 48.0h， 以49%的产率得到(R)-3-(4-(2-(2-methyl-[1,3,4]oxadiazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-{([1,2,3]triazol-1-yl)methyl}oxazolidin-2-one
  参考文献：
  名称：

  Discovery of torezolid as a novel 5-hydroxymethyl-oxazolidinone antibacterial agent

  摘要：

  A series of novel substituted pyridyl phenyl oxazolidinone analogues were synthesized and their structure-activity relationship (SAR) was investigated based on in vitro and in vivo antibacterial activities. The minimum inhibitory concentrations (MICs) of the synthesized compounds against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) ranged from 0.12 to 2.0 mu g/mL, and against Haemophilus influenzae (Hi) from 2.0 to 8.0 mu g/mL. Compared to linezolid, only four compounds (11, 12, 21 and 29) showed higher in vitro antibacterial activities and better in vivo protective effects in mice. To improve the aqueous solubility, various prodrugs of compound 11 (DA-7157), which exerted a potency that was enhanced by 2-8-fold compared to that of linezolid, were synthesized. Among the prodrugs, the phosphate compound 42 exhibited excellent aqueous solubility (>50 mg/mL in DW) and good pharmacokinetic profiles, along with better in vivo efficacy than linezolid. This compound 42 is currently undergoing clinical trials with the brand name Torezolid. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.014
• 作为产物：
  描述：

  2-(5-溴吡啶-2-基)-5-甲基-1,3,4-恶二唑 在 bis-triphenylphosphine-palladium(II) chloride 、 三乙胺 、 lithium chloride 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (R)-3-(4-(2-(2-methyl-[1,3,4]oxadiazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-(methanesulfonyloxymethyl)oxazolidin-2-one
  参考文献：
  名称：

  Discovery of torezolid as a novel 5-hydroxymethyl-oxazolidinone antibacterial agent

  摘要：

  A series of novel substituted pyridyl phenyl oxazolidinone analogues were synthesized and their structure-activity relationship (SAR) was investigated based on in vitro and in vivo antibacterial activities. The minimum inhibitory concentrations (MICs) of the synthesized compounds against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) ranged from 0.12 to 2.0 mu g/mL, and against Haemophilus influenzae (Hi) from 2.0 to 8.0 mu g/mL. Compared to linezolid, only four compounds (11, 12, 21 and 29) showed higher in vitro antibacterial activities and better in vivo protective effects in mice. To improve the aqueous solubility, various prodrugs of compound 11 (DA-7157), which exerted a potency that was enhanced by 2-8-fold compared to that of linezolid, were synthesized. Among the prodrugs, the phosphate compound 42 exhibited excellent aqueous solubility (>50 mg/mL in DW) and good pharmacokinetic profiles, along with better in vivo efficacy than linezolid. This compound 42 is currently undergoing clinical trials with the brand name Torezolid. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.014