5(R)-3-(4-(1-(tert-butoxycarbonyl)[1,2,5]triazepan-5-yl)-3,5-difluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)oxazolidin-2-one | 1443005-65-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5(R)-3-(4-(1-(tert-butoxycarbonyl)[1,2,5]triazepan-5-yl)-3,5-difluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)oxazolidin-2-one
• 英文别名: tert-butyl 5-[2,6-difluoro-4-[(5R)-2-oxo-5-(triazol-1-ylmethyl)-1,3-oxazolidin-3-yl]phenyl]-1,2,5-triazepane-1-carboxylate
• CAS: 1443005-65-9
• 化学式: C₂₁H₂₇F₂N₇O₄
• 分子量: 479.487
• InChiKey: QUCUZTMPAOAXTN-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5(R)-3-(4-(1-(tert-butoxycarbonyl)[1,2,5]triazepan-5-yl)-3,5-difluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)oxazolidin-2-one 在 盐酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 (5R)-3-[3,5-difluoro-4-(1,2,5-triazepan-5-yl)phenyl]-5-(triazol-1-ylmethyl)-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Synthesis and in vitro/in vivo antibacterial activity of oxazolidinones having thiocarbamate at C-5 on the A-ring and an amide- or urea-substituted [1,2,5]triazepane or [1,2,5]oxadiazepane as the C-ring

  摘要：

  Oxazolidinones bearing a seven-membered [1,2,51triazepane or [1,2,51oxadiazepane heterocycle substituted with an amide or urea functionality as the C-ring and having a [1,2,3]triazole, a thiocarbamate, an isoxazole-3-ylamino, or a thioacetamide C-5 side chain unit on the A-ring instead of the typical acetamide were synthesized and their in vitro antibacterial activities towards various pathogens were evaluated. Several derivatives exhibited potent in vitro antibacterial activity toward not only Grampositive, but also Gram-negative and linezolid-resistant pathogens. The in vivo therapeutic effects of amide 11a and ureas 16e, 17a were 2- to 3-fold greater than that of linezolid in a systemic mouse infection model treated by intravenous administration. Furthermore, compounds 11a and 17a showed lower monoamine oxidase (MAO)-inhibitory activity than our previously reported potent oxazolidinone antibacterials 3a and 3b. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.002
• 作为产物：
  描述：

  5(R)-3-(4-(1-(benzyloxycarbonyl)-2-(tert-butoxycarbonyl)[1,2,5]triazepan-5-yl)-3,5-difluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)oxazolidin-2-one 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 24.0h， 以96%的产率得到5(R)-3-(4-(1-(tert-butoxycarbonyl)[1,2,5]triazepan-5-yl)-3,5-difluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)oxazolidin-2-one
  参考文献：
  名称：

  Antibacterial oxazolidinone analogues having a N-hydroxyacetyl-substituted seven-membered [1,2,5]triazepane or [1,2,5]oxadiazepane C-ring unit

  摘要：

  We synthesized a series of oxazolidinone analogues bearing a N-hydroxyacetyl-substituted [1,2,5]triazepane or [1,2,5]oxadiazepane C-ring unit as homologues of an earlier drug candidate, eperezolid. Several of these compounds exhibited potent in vitro antibacterial activities towards not only Gram-positive, but also Gram-negative and linezolid-resistant pathogens. Compounds 21a and 21b, bearing a thiocarbamate side chain, showed high in vivo activity against methicillin-resistant Staphylococcus aureus SR3637, together with a promising safety profile in terms of weak inhibition of monoamine oxidase and cytochrome P450 isozymes. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.003

文献信息

• Antibacterial oxazolidinone analogues having a N-hydroxyacetyl-substituted seven-membered [1,2,5]triazepane or [1,2,5]oxadiazepane C-ring unit
  作者：Hideyuki Suzuki、Iwao Utsunomiya、Koichi Shudo、Norio Fukuhara、Tsutomu Iwaki、Tatsuro Yasukata

  DOI：10.1016/j.ejmech.2013.03.003

  日期：2013.5

  We synthesized a series of oxazolidinone analogues bearing a N-hydroxyacetyl-substituted [1,2,5]triazepane or [1,2,5]oxadiazepane C-ring unit as homologues of an earlier drug candidate, eperezolid. Several of these compounds exhibited potent in vitro antibacterial activities towards not only Gram-positive, but also Gram-negative and linezolid-resistant pathogens. Compounds 21a and 21b, bearing a thiocarbamate side chain, showed high in vivo activity against methicillin-resistant Staphylococcus aureus SR3637, together with a promising safety profile in terms of weak inhibition of monoamine oxidase and cytochrome P450 isozymes. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Synthesis and in vitro/in vivo antibacterial activity of oxazolidinones having thiocarbamate at C-5 on the A-ring and an amide- or urea-substituted [1,2,5]triazepane or [1,2,5]oxadiazepane as the C-ring
  作者：Hideyuki Suzuki、Iwao Utsunomiya、Koichi Shudo、Norio Fukuhara、Tsutomu Iwaki、Tatsuro Yasukata

  DOI：10.1016/j.ejmech.2013.08.002

  日期：2013.11

  Oxazolidinones bearing a seven-membered [1,2,51triazepane or [1,2,51oxadiazepane heterocycle substituted with an amide or urea functionality as the C-ring and having a [1,2,3]triazole, a thiocarbamate, an isoxazole-3-ylamino, or a thioacetamide C-5 side chain unit on the A-ring instead of the typical acetamide were synthesized and their in vitro antibacterial activities towards various pathogens were evaluated. Several derivatives exhibited potent in vitro antibacterial activity toward not only Grampositive, but also Gram-negative and linezolid-resistant pathogens. The in vivo therapeutic effects of amide 11a and ureas 16e, 17a were 2- to 3-fold greater than that of linezolid in a systemic mouse infection model treated by intravenous administration. Furthermore, compounds 11a and 17a showed lower monoamine oxidase (MAO)-inhibitory activity than our previously reported potent oxazolidinone antibacterials 3a and 3b. (C) 2013 Elsevier Masson SAS. All rights reserved.