tert-butyl 4-{2-fluoro-4-[(5R)-2-oxo-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-3-yl]phenyl}piperazine-1-carboxylate | 371195-29-8

• 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: tert-butyl 4-{2-fluoro-4-[(5R)-2-oxo-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-3-yl]phenyl}piperazine-1-carboxylate
• 英文别名: (5R)-3-(4-(4-t-butoxycarbonylpiperazin-1-yl)-3-fluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)oxazolidin-2-one；tert-butyl 4-[2-fluoro-4-[(5R)-2-oxo-5-(triazol-1-ylmethyl)-1,3-oxazolidin-3-yl]phenyl]piperazine-1-carboxylate
• CAS: 371195-29-8
• 化学式: C₂₁H₂₇FN₆O₄
• 分子量: 446.482
• InChiKey: ZEMGMNBJXFCHJY-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  32
• 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：
  93
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-{2-fluoro-4-[(5R)-2-oxo-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-3-yl]phenyl}piperazine-1-carboxylate 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 (5R)-3-[4-[4-(3,5-dinitrobenzoyl)piperazin-1-yl]-3-fluorophenyl]-5-(triazol-1-ylmethyl)-1,3-oxazolidin-2-one
  参考文献：
  名称：

  不同取代基对三唑基甲基恶唑烷酮类抗菌活性的影响

  摘要：

  合成了许多在 4N-哌嗪位置具有不同取代基的 1,2,3-三唑基甲基哌嗪基恶唑烷酮衍生物，并评估了它们对一组敏感和耐药的革兰氏阳性菌和选定的革兰氏阴性菌的抗菌活性。用 5 元杂芳酰基和二硝基苯甲酰基部分取代可增强对葡萄球菌和肠球菌菌株的活性。此外，具有二硝基苯甲酰基 7n、7o 和 5-硝基呋喃酰基 7t 取代的化合物对卡他莫拉氏菌的效力是利奈唑胺的四到八倍。然而，在 4N-哌嗪位置取代胍基和其他水溶性官能团导致化合物缺乏抗菌活性。

  DOI：

  10.1002/ardp.201100332
• 作为产物：
  描述：

  (R)-tert-butyl 4-(4-(5-(azidomethyl)-2-oxooxazolidin-3-yl)-2-fluorophenyl)piperazine-1-carboxylate 、 2,5-降冰片二烯 以 1,4-二氧六环 为溶剂， 反应 6.0h， 生成 tert-butyl 4-{2-fluoro-4-[(5R)-2-oxo-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-3-yl]phenyl}piperazine-1-carboxylate
  参考文献：
  名称：

  Oxazolidinone derivatives with antibiotic activity

  摘要：

  公式(I)的化合物，或其药学上可接受的盐，或其体内水解酯，其中HET是一个N-连接的5-成员杂环芳基环，可选地在碳原子上被氧化或硫代氧基取代；和/或由1或2个（1-4C）烷基基团取代；和/或在一个可用的氮原子上由（1-4C）烷基基团取代；或者HET是一个N-连接的6-成员杂环芳基环，总共包含最多三个氮杂原子，可选地在碳原子上如上所述取代；Q是选自，例如，Q12R2和R3独立地是氢或氟；T是选自一系列基团，例如，如下式（TC5）3其中Rc是，例如，R13CO—，R13SO2—或R13CS—；其中R13是，例如，可选地取代的（1-10C）烷基或R14C(O)O(1-6C)烷基，其中R14是可选地取代的（1-10C）烷基；作为抗菌剂是有用的；并描述了它们的制备方法和含有它们的药物组合物。

  公开号：

  US20030216373A1

文献信息

• Structure-Antibacterial Activity Relationships of N-Substituted-(d-/l-Alaninyl) 1H-1,2,3-Triazolylmethyl Oxazolidinones
  作者：Oludotun Phillips、Edet Udo、Roselyn D’silva

  DOI：10.3390/scipharm86040042

  日期：——

  Bacterial resistance towards the existing class of antibacterial drugs continues to increase, posing a significant threat to the clinical usefulness of these drugs. These increasing and alarming rates of antibacterial resistance development and the decline in the number of new antibacterial drugs’ approval continue to serve as a major impetus for research into the discovery and development of new antibacterial agents. We synthesized a series of d-/l-alaninyl substituted triazolyl oxazolidinone derivatives and evaluated their antibacterial activity against selected standard Gram-positive and Gram-negative bacterial strains. Overall, the compounds showed moderate to strong antibacterial activity. Compounds 9d and 10d (d- and l-alaninyl derivatives bearing the 3,5-dinitrobenzoyl substituent), 10e (l-alaninyl derivative bearing the 5-nitrofurancarbonyl group) and 9f and 10f (d- and l-alaninyl derivatives bearing the 5-nitrothiophene carbonyl moiety) demonstrated antibacterial activity (MIC: 2 µg/mL) against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Moraxella catarrhalis standard bacterial strains. No significant differences were noticeable between the antibacterial activity of the d- and l-alaninyl derivatives as a result of the stereochemistry of the compounds.

  对现有类别的抗菌药物的细菌耐药性持续增加，对这些药物的临床有效性构成重大威胁。这种抗菌耐药性发展的不断增加和令人担忧的速度，以及新抗菌药物批准数量的下降，继续促使对新抗菌剂的发现和开发进行研究。我们合成了一系列d-/l-丙氨酸取代的三唑基噁唑啉酮衍生物，并评估它们对选定的标准革兰氏阳性和阴性细菌菌株的抗菌活性。总体而言，这些化合物显示出中等到强的抗菌活性。化合物9d和10d（带有3,5-二硝基苯甲酰取代基的d-和l-丙氨酸衍生物）、10e（带有5-硝基呋喃甲酰基团的l-丙氨酸衍生物）以及9f和10f（带有5-硝基噻吩羰基的d-和l-丙氨酸衍生物）表现出抗菌活性（MIC：2 µg/mL），对金黄色葡萄球菌、表皮葡萄球菌、肠球菌和喜冷假单胞菌标准细菌菌株具有抗菌活性。由于化合物的立体化学结构，d-和l-丙氨酸衍生物的抗菌活性之间没有明显差异。
• [EN] OXAZOLIDINONE DERIVATIVES AS ANTIMICROBIALS<br/>[FR] DERIVES D'OXAZOLIDINONE A ACTIVITE ANTIMICROBIENNE
  申请人：RANBAXY LAB LTD

  公开号：WO2006035283A1

  公开（公告）日：2006-04-06

  The present invention relates to substituted phenyl oxazolidinones and processes for preparing thereof. This invention also relates to pharmaceutical compositions comprising compounds of the present invention. Such compounds can be useful antimicrobial agents that can be particularly effective against a number of human and veterinary pathogens, including gram-positive aerobic bacteria (e.g., multiple-resistant staphylococci, streptococci and enterococci), anaerobic organisms (e.g., Bacterioides spp. and Clostridia spp. species), and acid-fast organisms (e.g., Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium spp).Formula (I).

  本发明涉及取代苯基噁唑烷酮及其制备方法。本发明还涉及包含本发明化合物的药物组合物。这些化合物可以是有用的抗微生物剂，特别是对许多人类和兽医病原体具有特效，包括革兰氏阳性厌氧细菌（例如，多耐药葡萄球菌、链球菌和肠球菌）、厌氧菌（例如，拟杆菌属和梭菌属物种）和耐酸菌（例如，结核分枝杆菌、分枝杆菌和分枝杆菌属）。公式（I）。
• Synthesis and antibacterial activities of N-substituted-glycinyl 1H-1,2,3-triazolyl oxazolidinones
  作者：Oludotun A. Phillips、Edet E. Udo、Mohammed E. Abdel-Hamid、Reny Varghese

  DOI：10.1016/j.ejmech.2013.05.041

  日期：2013.8

  A series of 1H-1,2,3-triazolyl piperazino oxazolidinone analogs with optionally varied glycinyl substitutions were synthesized and their antibacterial activity assessed against a panel of susceptible and resistant Gram-positive and selected Gram-negative bacteria including clinical isolates. The N-aroyl- and N-heteroaroyl-glycinyl (MIC: 0.06-4 mu g/ml) derivatives were more potent than the N-acylglycinyl (2 -8 mu g/ml) derivatives against all Gram-positive bacteria tested. Nitro substitution on aryl and heteroaryl rings significantly enhanced activity against Gram-positive bacteria, as noted with the 3,5-dinitrobenzoyl (6m and 6n) and 5-nitro-2-furoyl (6u and 6v) derivatives with MIC ranges of and 0.25-0.5 and 0.06 -0.5 mu g/ml, respectively. These nitro analogs also showed more potent extended activity against Moraxella catarrhalis, with MICs ranges of 0.25-1 mu g/ml, compared to linezolid (MIC: 8 mu g/ml). Hence, the presence of the N-aroyl and/or N-heteroaroyl glycinyl structural motifs as spacer group could significantly enhance the antibacterial activities of 1H-1,2,3-triazolyl oxazolidinone class of compounds. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Novel and potent oxazolidinone antibacterials featuring 3-indolylglyoxamide substituents
  作者：Mohamed Takhi、Gurpreet Singh、C. Murugan、Nirvesh Thaplyyal、Soma Maitra、K.M. Bhaskarreddy、P.V.S. Amarnath、Arundhuti Mallik、T. Harisudan、Ravi Kumar Trivedi、K. Sreenivas、N. Selvakumar、Javed Iqbal

  DOI：10.1016/j.bmcl.2008.03.043

  日期：2008.9

  Novel oxazolidinone antibacterials bearing a variety of 3-indolylglyoxamide substituents have been explored in an effort to improve the spectrum and potency of this class of agents. A subclass of this series was also made with the diversity at C-5 terminus. These derivatives have been screened against a panel of clinically relevant Gram-positive pathogens and fastidious Gram-negative organisms. Several analogs in this series were identified with in vitro activity superior to linezolid ( MIC = 0.25-2 mu g/ mL). Compounds 10a, 10c, 10e and 10f displayed activity against linezolid resistant Gram-positive organisms (MIC = 2-4 mu g/ mL). Selected oxazolidinones were evaluated for in vivo efficacy against a mouse systemic infection model. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis and structure–antibacterial activity of triazolyl oxazolidinones containing long chain acyl moiety
  作者：Oludotun A. Phillips、Edet E. Udo、Santhosh M. Samuel

  DOI：10.1016/j.ejmech.2007.07.006

  日期：2008.5

  A series of new piperazinyl 5-triazolyimethyl oxazolidinones containing long chain acyl group at the piperazine N-4-position were synthesized and evaluated against a panel of standard and clinical isolates of Gram-positive and Gram-negative bacteria. Derivatives having long chain acyl groups with nine or more number of carbon atoms showed significant decrease in antibacterial activity. Antibacterial activity correlated positively with heat of formation of the compounds, but correlated negatively with Clog P values, surface area, ovality and molecular volume. However, no significant correlation was observed between activity and E-LUMO, E-HOMO and dipole, respectively. (C) 2007 Elsevier Masson SAS. All rights reserved.