(R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3-fluoro-4-(piperazin-1-yl)phenyl)oxazolidin-2-one | 371195-30-1

• 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: (R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3-fluoro-4-(piperazin-1-yl)phenyl)oxazolidin-2-one
• 英文别名: (5R)-3-(4-(Piperazin-1-yl)-3-fluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)oxazolidin-2-one；(5R)-3-(3-fluoro-4-piperazin-1-ylphenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one；(5R)-3-(3-fluoro-4-piperazin-1-ylphenyl)-5-(triazol-1-ylmethyl)-1,3-oxazolidin-2-one
• CAS: 371195-30-1
• 化学式: C₁₆H₁₉FN₆O₂
• 分子量: 346.364
• InChiKey: XHRLWDGTEZCNOW-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  75.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3-fluoro-4-(piperazin-1-yl)phenyl)oxazolidin-2-one 、 2-三氟甲基苯磺酰氯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (5R)-3-[3-fluoro-4-[4-[2-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]phenyl]-5-(triazol-1-ylmethyl)-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Synthesis and antibacterial activity of oxazolidinones containing triazolyl group

  摘要：

  A new series of oxazolidinones containing triazolyl group has been synthesized and tested for in vitro antibacterial activity by MIC determination against a panel of resistant and susceptible Gram-positive organisms. Most of the analogs in this series displayed activity superior to linezolid and vancomycin in vitro. Further, in vivo efficacies of the selected oxazolidinones were also disclosed herein. (c) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.01.012
• 作为产物：
  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 三氟乙酸 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成 (R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3-fluoro-4-(piperazin-1-yl)phenyl)oxazolidin-2-one
  参考文献：
  名称：

  [EN] OXAZOLIDINONE DERIVATIVES AS ANTIMICROBIALS
  [FR] DERIVES D'OXAZOLIDINONE A ACTIVITE ANTIMICROBIENNE

  摘要：

  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）。

  公开号：

  WO2006035283A1

文献信息

• Structure–antibacterial activity of arylcarbonyl- and arylsulfonyl-piperazine 5-triazolylmethyl oxazolidinones
  作者：Oludotun A. Phillips、Edet E. Udo、Ahmed A.M. Ali、Santhosh M. Samuel

  DOI：10.1016/j.ejmech.2006.10.005

  日期：2007.2

  and electron-donating groups on the phenyl ring in the arylcarbonyl series did not alter antibacterial activity significantly. However, in the arylsufonyl series, methyl substitution on the phenyl ring resulted in the loss of antibacterial activity. Antibacterial activity could not be directly correlated with the calculated partition coefficient (ClogP) values in this series of compounds.

  合成了一系列新颖的芳基羰基和芳基磺酰基哌嗪基5-三唑基甲基恶唑烷酮，并针对一组革兰氏阳性和革兰氏阴性细菌临床分离株进行了测试。芳基羰基恶唑烷酮衍生物在体外对敏感和耐药的革兰氏阳性病原菌具有很强的抗菌活性，并且比芳基磺酰基衍生物具有更高的活性。取代芳基羰基系列的苯环上的吸电子和供电子基团并没有显着改变抗菌活性。但是，在芳基磺酰基系列中，苯环上的甲基取代导致抗菌活性的丧失。在这一系列化合物中，抗菌活性不能与计算的分配系数（ClogP）值直接相关。
• Oxazolidinone derivatives with antibiotic activity
  申请人：——

  公开号：US20030216373A1

  公开（公告）日：2003-11-20

  Compounds of the formula (I), or a pharmaceutically acceptable salt, or an in-vivo-hydrolysable ester thereof, 1 wherein HET is an N-linked 5-membered heteroaryl ring, optionally substituted on a C atom by an oxo or thioxo group; and/or by 1 or 2 (1-4C)alkyl groups; and/or on an available nitrogen atom by (1-4C)alkyl; or HET is an N-linked 6-membered heteroaryl ring containing up to three nitrogen heteroatoms in total, optionally substituted on a C atom as above; Q is selected from, for example, Q1 2 R 2 and R 3 are independently hydrogen or fluoro; T is selected from a range of groups, for example, of formula (TC 5 ) 3 wherein Rc is, for example, R 13 CO—, R 13 SO 2 — or R 13 CS—; wherein R 13 is, for example, optionally substituted (1-10C)alkyl or R 14 C(O)O(1-6C)alkyl wherein R 14 is optionally substituted (1-10C)alkyl; are useful as antibacterial agents; and processes for their manufacture and pharmaceutical compositions containing them are described.

  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。
• [EN] OXAZOLIDINONE DERIVATIVES WITH ANTIBIOTIC ACTIVITY<br/>[FR] DERIVES D'OXAZOLIDINONE AYANT UNE ACTIVITE ANTIBIOTIQUE
  申请人：ASTRAZENECA AB

  公开号：WO2001081350A1

  公开（公告）日：2001-11-01

  Compounds of formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, wherein HET is an N-linked 5-membered heteroaryl ring, optionally substituted on a C atom by an oxo or thioxo group; and/or by 1 or 2(1-4C) alkyl groups; and/or on an available nitrogen atom by (1-4C)alkyl; or HET is an N-linked 6-membered heteroaryl ring containing up to three nitrogen heteroatoms in total, optionally substituted on a C atom as above; Q is selected from, for example, (Q1), R?2 and R3¿ are independently hydrogen or fluoro; T is selected from a range of groups, for example, of formula (TC5), wherein Rc is, for example, R?13CO-, R13SO¿2- or R13CS-; wherein R13 is, for example, optionally substituted (1-10C)alkyl or R14C(O)O(1-6C)alkyl wherein R14 is optionally substituted (1-10C)alkyl; are useful as antibacterial agents; and processes for their manufacture and pharmaceutical compositions containing them are described.

  公式（I）的化合物，或其药学上可接受的盐，或其体内可水解的酯，其中HET是N-连接的5成员杂芳环，可选择在C原子上由氧或硫代氧基取代; 和/或由1或2（1-4C）烷基取代; 和/或在可用的氮原子上由（1-4C）烷基取代; 或者HET是N-连接的6成员杂芳环，总共包含最多三个氮杂原子，可选择在C原子上如上所述取代; Q是从（Q1）中选择，R？2和R3¿独立地为氢或氟; T是从一系列基团中选择，例如公式（TC5），其中Rc是例如R？13CO-，R13SO¿2-或R13CS-;其中R13例如是可选择取代的（1-10C）烷基或R14C（O）O（1-6C）烷基，其中R14是可选择取代的（1-10C）烷基; 适用于抗菌剂; 并描述了其制造过程和含有它们的制药组合物。
• 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.