(S)-N-((3-(3-fluoro-4-(piperazin-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamidehydrochloride

• 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: (S)-N-((3-(3-fluoro-4-(piperazin-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamidehydrochloride
• 英文别名: 3 PNU-99388；N-({(5S)-3-[3-fluoro-4-(1-piperaziny-1)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide hydrochloride；(S)-N-[[3-[3-fluoro-4(-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide hydrochloride；(S)-N-[[3-[3-Fluoro-4-(1-piperazinyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide hydrochloride；N-[[(5S)-3-(3-fluoro-4-piperazin-1-ylphenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide;hydrochloride
• 化学式: C₁₆H₂₁FN₄O₃*ClH
• 分子量: 372.827
• InChiKey: QZSQEFFAXPLQIS-ZOWNYOTGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.12
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  73.9
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-N-((3-(3-fluoro-4-(piperazin-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamidehydrochloride 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 N-[[(5S)-3-[3-氟-4-[4-(2-羟基乙酰基)-1-哌嗪基]苯基]-2-氧代-5-噁唑烷基]甲基]-乙酰胺
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of U-100592 and U-100766, Two Oxazolidinone Antibacterial Agents for the Potential Treatment of Multidrug-Resistant Gram-Positive Bacterial Infections

  摘要：

  Bacterial resistance development has become a very serious clinical problem for many classes of antibiotics. The 3-aryl-2-oxazolidinones are a relatively new class of synthetic antibacterial agents, having a new mechanism of action which involves very early inhibition of bacterial protein synthesis. We have prepared two potent, synthetic oxazolidinones, U-100592 and U-100766, which are currently in clinical development for the treatment of serious multidrug-resistant Gram-positive bacterial infections caused by strains of staphylococci, streptococci, and enterococci. The in vitro and in vivo (po and iv) activities of U-100592 and U-100766 against representative strains are similar to those of vancomycin. U-100592 and U-100766 demonstrate potent in vitro activity against Mycobacterium tuberculosis. A novel and practical asymmetric synthesis of (5S)-(acetamidomethyl)-2-oxazolidinones has been developed and is employed for the synthesis of U-100592 and U-100766. This involves the reaction of N-lithioarylcarbamates with (R)-glycidyl butyrate, resulting in excellent yields and high enantiomeric purity of the intermediate (R)-5-(hydroxymethyl)-2-oxazolidinones,

  DOI：

  10.1021/jm9509556
• 作为产物：
  描述：

  N-carbobenzoxy-3-fluoro-4-(N-carbobenzoxypiperazin-1-yl)aniline 在 palladium on activated charcoal 吡啶 、 正丁基锂 、 二氯甲烷 、 氢气 、 三乙胺 、 甲胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 63.5h， 生成 (S)-N-((3-(3-fluoro-4-(piperazin-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamidehydrochloride
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of U-100592 and U-100766, Two Oxazolidinone Antibacterial Agents for the Potential Treatment of Multidrug-Resistant Gram-Positive Bacterial Infections

  摘要：

  Bacterial resistance development has become a very serious clinical problem for many classes of antibiotics. The 3-aryl-2-oxazolidinones are a relatively new class of synthetic antibacterial agents, having a new mechanism of action which involves very early inhibition of bacterial protein synthesis. We have prepared two potent, synthetic oxazolidinones, U-100592 and U-100766, which are currently in clinical development for the treatment of serious multidrug-resistant Gram-positive bacterial infections caused by strains of staphylococci, streptococci, and enterococci. The in vitro and in vivo (po and iv) activities of U-100592 and U-100766 against representative strains are similar to those of vancomycin. U-100592 and U-100766 demonstrate potent in vitro activity against Mycobacterium tuberculosis. A novel and practical asymmetric synthesis of (5S)-(acetamidomethyl)-2-oxazolidinones has been developed and is employed for the synthesis of U-100592 and U-100766. This involves the reaction of N-lithioarylcarbamates with (R)-glycidyl butyrate, resulting in excellent yields and high enantiomeric purity of the intermediate (R)-5-(hydroxymethyl)-2-oxazolidinones,

  DOI：

  10.1021/jm9509556

文献信息

• [EN] N-(4-(PIPERAZIN-1-YL)-PHENYL-2-OXAZOLIDINONE-5-CARBOXAMIDE DERIVATES AND RELATED COMPOUNDS AS ANTIBACTERIAL AGENTS<br/>[FR] DERIVES DE N-(4-(PIPERAZINE-1-YL)-PHENYL-2-OXAZOLIDINONE-5-CARBOXAMIDES ET COMPOSES ASSOCIES SERVANT D'AGENTS ANTIBACTERIENS
  申请人：UPJOHN CO

  公开号：WO2004045616A1

  公开（公告）日：2004-06-03

  The present invention provides antibacterial agents having the formula I described herein. or-pharmaceutically acceptable salts thereof wherein: A is a structure i, ii, iii, or iv, W is N(H)C(X)-R,. Het, or -Y HET, in which the Hot or Y HET is optionally substituted with =S or '0, provided that when A is structure iv, W is not - Y--1-MT or Het;

  本发明提供了具有以下式I的抗菌剂，或其药学上可接受的盐，其中：A是结构i、ii、iii或iv，W是N(H)C(X)-R、Het或-Y HET，在其中Hot或Y HET可以选择地被=S或'0取代，但当A是结构iv时，W不是-Y--1-MT或Het。
• Piperazinyl Oxazolidinone Antibacterial Agents Containing a Pyridine, Diazene, or Triazene Heteroaromatic Ring
  作者：John A. Tucker、Debra A. Allwine、Kevin C. Grega、Michael R. Barbachyn、Jennifer L. Klock、Jenifer L. Adamski、Steven J. Brickner、Douglas K. Hutchinson、Charles W. Ford、Gary E. Zurenko、Robert A. Conradi、Phillip S. Burton、Randy M. Jensen

  DOI：10.1021/jm980274l

  日期：1998.9.1

  Oxazolidinones are a novel class of synthetic antibacterial agents active against gram-positive organisms including methicillin-resistant Staphylococcus aureus as well as selected anaerobic organisms. Important representatives of this class include the morpholine derivative linezolid 2, which is currently in phase III clinical trials, and the piperazine derivative eperezolid 3. As part of an investigation

  恶唑烷酮是一类新型的合成抗菌剂，对革兰氏阳性生物具有活性，包括耐甲氧西林的金黄色葡萄球菌以及某些厌氧生物。此类药物的重要代表包括吗啉衍生物利奈唑胺2（目前正在进行III期临床试验）和哌嗪衍生物依哌唑胺3。作为研究与结构相关的恶唑烷酮的结构-活性关系的一部分，我们准备并评估了一系列哌嗪基恶唑烷酮的抗菌特性，其中哌嗪基环的远端氮被六元杂芳族环取代。具有MIC值的化合物
• N-aryl-2-oxazolidinone-5-carboxamides and their derivatives
  申请人：——

  公开号：US20040204463A1

  公开（公告）日：2004-10-14

  The present invention provides antibacterial agents having the formula I described herein.

  本发明提供了具有以下式I的抗菌剂。
• [EN] OXAZOLIDINONE DERIVATIVES AS ANTIMICROBIALS<br/>[FR] DERIVES D'OXAZOLIDINONE UTILISES COMME AGENTS ANTIMICROBIENS
  申请人：RANBAXY LAB LTD

  公开号：WO2004014392A1

  公开（公告）日：2004-02-19

  The present invention relates to certain substituted phenyl oxazolidinones and to processes for the synthesis of the same. This invention also relates to pharmaceutical compositions containing the compounds of the present invention as antimicrobials. The compounds are useful antimicrobial agents, effective against a number of human and veterinary pathogens, including gram-positive aerobic bacteria such as multiple-resistant staphylococci, streptococci and enterococci as well as anaerobic organisms such as Bacterioides spp. and Clostridia spp. species, and acid fast organisms such as Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium spp.

  本发明涉及某些取代苯基噁唑烷酮及其合成方法。本发明还涉及含有本发明化合物作为抗微生物剂的药物组合物。这些化合物是有用的抗微生物剂，对许多人类和兽医病原体具有有效作用，包括革兰氏阳性的好氧菌，如多重耐药葡萄球菌、链球菌和肠球菌，以及厌氧菌，如拟杆菌属和梭菌属菌种，以及酸性快速菌，如结核分枝杆菌、非结核分枝杆菌和分枝杆菌属菌种。
• Process to prepare oxazolidinones
  申请人：Pharmacia & Upjohn Company

  公开号：US05837870A1

  公开（公告）日：1998-11-17

  The present invention includes processes for producing 5-hydroxymethyl substituted oxazolidinone alcohols (III) from carbamates (IIA) or a trifluoroacetamide (IIB) using a dihydroxy compound (I) or glycidol (IV) starting material and for the transformation of the hydroxymethyl substituted oxazolidinone alcohols (III) to the corresponding amino compounds, 5-aminomethyl substituted oxazolidinone amines (VII) which are acylated to form commercially useful antibacterial 5-acylamidomethyl substituted oxazolidinone (VIII).

  本发明涉及使用二羟基化合物(I)或环氧丙烷醇(IV)起始物从碳酸酯(IIA)或三氟乙酰胺(IIB)中生产5-羟甲基取代的噁唑烷醇(III)的工艺，并将羟甲基取代的噁唑烷醇(III)转化为相应的氨基化合物，5-氨基甲基取代的噁唑烷胺(VII)，然后酰化形成商业上有用的抗菌5-酰胺基甲基取代的噁唑烷酮(VIII)。