5(S)-(aminomethyl)-3-(3-fluoro-4-(1-(tert-butoxycarbonyl)[1,2,5]triazepan-5-yl)phenyl)oxazolidin-2-one | 1443005-43-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5(S)-(aminomethyl)-3-(3-fluoro-4-(1-(tert-butoxycarbonyl)[1,2,5]triazepan-5-yl)phenyl)oxazolidin-2-one
• 英文别名: tert-butyl 5-[4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]-1,2,5-triazepane-1-carboxylate
• CAS: 1443005-43-3
• 化学式: C₁₉H₂₈FN₅O₄
• 分子量: 409.461
• InChiKey: QJSNTMMSWIZFSB-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5(S)-(aminomethyl)-3-(3-fluoro-4-(1-(tert-butoxycarbonyl)[1,2,5]triazepan-5-yl)phenyl)oxazolidin-2-one 在 吡啶 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 20.34h， 生成
  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
• 作为产物：
  描述：

  [1,2,5]triazepane-1-carboxylic acid tert-butyl ester 在 正丁基锂 、 sodium azide 、 palladium 10% on activated carbon 、 氢气 、 sodium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， -78.0~90.0 ℃ 、101.33 kPa 条件下， 反应 88.01h， 生成 5(S)-(aminomethyl)-3-(3-fluoro-4-(1-(tert-butoxycarbonyl)[1,2,5]triazepan-5-yl)phenyl)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

• Antimicrobial oxazolidinone derivatives
  申请人：Research Foundation Itsuu Laboratory

  公开号：EP2181993A1

  公开（公告）日：2010-05-05

  A compound of the formula: or a pharmaceutically acceptable salt or solvate thereof, wherein Ring A is (A-1) at least 7-membered monocyclic hetero ring containing at least three N atoms; (A-2) at least 6-membered monocyclic hetero ring containing at least two N atoms and at least one O atom; or (A-3) at least 7-membered monocyclic hetero ring containing at least two N atoms and at least one S atom, wherein said monocyclic hetero ring is optionally substituted, and said monocyclic hetero ring is optionally condensed with another ring, X1 is a single bond, or a hetero atom-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 hetero atom-containing group; Ring B is optionally substituted carbocycle or optionally substituted heterocycle; R1 is hydrogen, or an organic residue which is able to bind to the 5-position of oxazolidinone ring in oxazolidinone antimicrobial agent.

  式中的化合物： 或其药学上可接受的盐或溶液，其中 环 A 是 (A-1) 至少含有三个 N 原子的 7 元单环杂环； (A-2) 至少含有两个 N 原子和至少一个 O 原子的 6 元单环杂环；或 (A-3) 至少含有两个 N 原子和至少一个 S 原子的 7 元单环杂环，其中所述单环杂环任选被取代，且所述单环杂环任选与另一个环缩合、 X1为单键，或选自-O-、-S-、-NR2-、-CO-、-CS-、-CONR3-、-NR4CO-、-SO2NR5-和-NR6SO2-组成的含杂原子基团，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； 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。
• 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。
• 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.