5(R)-3-(4-(10-oxo-5,6,8,9-tetrahydro-10H-4,4b,7,9a-tetraazabenzo[a]azulen-7-yl)-3-fluorophenyl)-5-(1,2,3-tri-azol-1-ylmethyl)oxazolidin-2-one | 1138148-11-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: 5(R)-3-(4-(10-oxo-5,6,8,9-tetrahydro-10H-4,4b,7,9a-tetraazabenzo[a]azulen-7-yl)-3-fluorophenyl)-5-(1,2,3-tri-azol-1-ylmethyl)oxazolidin-2-one
• 英文别名: (5R)-3-[3-fluoro-4-(8-oxo-1,3,9,12-tetrazatricyclo[7.5.0.02,7]tetradeca-2(7),3,5-trien-12-yl)phenyl]-5-(triazol-1-ylmethyl)-1,3-oxazolidin-2-one
• CAS: 1138148-11-4
• 化学式: C₂₂H₂₁FN₈O₃
• 分子量: 464.459
• InChiKey: BZBMCXNNGKHYCO-INIZCTEOSA-N

物化性质

• 熔点：
  166.5-168.5 °C
• 沸点：
  707.6±70.0 °C(predicted)
• 密度：
  1.61±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  99.9
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以84.2 mg的产率得到5(R)-3-(4-(10-oxo-5,6,8,9-tetrahydro-10H-4,4b,7,9a-tetraazabenzo[a]azulen-7-yl)-3-fluorophenyl)-5-(1,2,3-tri-azol-1-ylmethyl)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

文献信息

• OXAZOLIDINONE DERIVATIVE HAVING 7-MEMBERED HETERO RING
  申请人：Research Foundation Itsuu Laboratory

  公开号：EP2208729A1

  公开（公告）日：2010-07-21

  The present invention provides a novel oxazolidinone derivative of the formula (I): wherein Ring A is (A-1) a 7-membered monocyclic heterocycle containing three N atoms; (A-2) a 7-membered monocyclic heterocycle containing two N atoms and one O atom; or (A-3) a 7-membered monocyclic heterocycle containing two N atoms and one S atom, SO or SO2, wherein said monocyclic heterocycle is optionally substituted, optionally unsaturated and optionally fused with another ring; X1 is a single bond, or a heteroatom-containing group selected from the group consisting of -O-, -S-, -NR2-, -CO-, -CS-, -CONR3-, -NR4CO-, -SO2NR5-, and -NR6SO2-, wherein R2, R3, R4, R5 and R6 are independently hydrogen or lower alkyl, or lower alkylene or lower alkenylene each optionally interrupted by said heteroatom-containing group; Ring B is optionally substituted carbocycle or optionally substituted heterocycle; and R1 is hydrogen, or an organic residue which is able to bind to the 5-position of the oxazolidinone ring in oxazolidinone antimicrobial agents, pharmaceutically acceptable salts and solvates thereof which are useful as an antibacterial agent.

  本发明提供了一种式 (I) 的新型噁唑烷酮衍生物： 其中 环 A 是 (A-1) 包含三个 N 原子的 7 元单环杂环； (A-2) 含两个 N 原子和一个 O 原子的 7 元单环杂环；或 (A-3) 含两个 N 原子和一个 S 原子、SO 或 SO2 的 7 元单环杂环、 其中所述单环杂环可选被取代、可选不饱和、可选与另一个环融合； X1 是单键，或选自以下组成的含杂原子基团：-O-、-S-、-NR2-、-CO-、-CS-、-CONR3-、-NR4CO-、-SO2NR5- 和 -NR6SO2-，其中 R2、R3、R4、R5 和 R6 独立地为氢或低级烷基，或低级亚烷基或低级亚烯基，各自任选被所述含杂原子基团打断； 环 B 是任选取代的碳环或任选取代的杂环；以及 R1 是氢，或能够与噁唑烷酮抗菌剂中噁唑烷酮环的 5 位结合的有机残基、 可用作抗菌剂的其药学上可接受的盐和溶剂。
• US8530646B2
  申请人：——

  公开号：US8530646B2

  公开（公告）日：2013-09-10
• 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.