(R)-<3-<3-fluoro-4-(4-thiomorpholinyl)phenyl>-2-oxo-5-oxazolidinyl>methyl azide | 168828-74-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻嗪类
• 英文名称: (R)-<3-<3-fluoro-4-(4-thiomorpholinyl)phenyl>-2-oxo-5-oxazolidinyl>methyl azide
• 英文别名: (R)-5-azidomethyl-3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]oxazolidine-2-one；(R)-5-(azidomethyl)-3-(3-fluoro-4-thiomorpholinophenyl)oxazolidin-2-one；(R)-5-azidomethyl-3-[3-fluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxooxazolidine；(R)-[[3-(3-fluoro4-(4-thiomorpholinyl)phenyl)-2-oxo-5-oxazolidinyl]methyl]azide；(5R)-5-(Azidomethyl)-3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxazolidinone；(5R)-5-(azidomethyl)-3-(3-fluoro-4-thiomorpholin-4-ylphenyl)-1,3-oxazolidin-2-one
• CAS: 168828-74-8
• 化学式: C₁₄H₁₆FN₅O₂S
• 分子量: 337.378
• InChiKey: ALWZKASVMYTTKY-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 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：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-<3-<3-fluoro-4-(4-thiomorpholinyl)phenyl>-2-oxo-5-oxazolidinyl>methyl azide 在 吡啶 、 水 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 sutezolid
  参考文献：
  名称：

  Identification of a Novel Oxazolidinone (U-100480) with Potent Antimycobacterial Activity

  摘要：

  During the course of our investigations in the oxazolidinone antibacterial agent area, we have identified a subclass with especially potent in vitro activity against mycobacteria. The salient structural feature of these oxazolidinone analogues, 6 (U-100480), 7 (U-101603), and 8 (U-101244), is their appended thiomorpholine moiety. The rational design, synthesis, and evaluation of the in vitro antimycobacterial activity of these analogues is described. Potent activity against a screening strain of Mycobacterium tuberculosis was demonstrated by 6 and 7 (minimum inhibitory concentrations or MIC's less than or equal to 0.125 mu g/mL). Oxazolidinones 6 and 8 exhibit MIC(90) values of 0.50 mu g/mL or less against a panel of organisms consisting of five drug-sensitive and five multidrug-resistant strains of M. tuberculosis, with 6 being the most active congener. Potent in vitro activity against other mycobacterial species was also demonstrated by 6. For example, 6 exhibited excellent in vitro activity against multiple clinical isolates of Mycobacterium avium complex (MIC's = 0.5-4 mu g/mL). Orally administered 6 displays in vivo efficacy against M. tuberculosis and M. avium similar to that of clinical comparators isoniazid and azithromycin, respectively. Consideration of these factors, along with a favorable pharmacokinetic and chronic toxicity profile in rats, suggests that 6 (U-100480) is a promising antimycobacterial agent.

  DOI：

  10.1021/jm950956y
• 作为产物：
  描述：

  3,4-二氟硝基苯 在 正丁基锂 、 sodium azide 、 palladium on activated charcoal 、 氢气 、 碳酸氢钠 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 49.0h， 生成 (R)-<3-<3-fluoro-4-(4-thiomorpholinyl)phenyl>-2-oxo-5-oxazolidinyl>methyl azide
  参考文献：
  名称：

  新型恶唑烷酰胺/磺酰胺偶联物的设计，合成及其对抗菌活性的影响

  摘要：

  摘要考虑到产生用于未来药物开发的新化合物，我们已经合成了芳基酰胺和芳基磺酰胺衍生物的恶唑烷酮文库。这些化合物在体外针对敏感和耐药的革兰氏阳性菌（金黄色葡萄球菌和枯草芽孢杆菌），革兰氏阴性菌（铜绿假单胞菌），真菌（白色念珠菌）和结核分枝杆菌（Mtb）进行了筛选。其中，对10d和11a化合物已针对12种真菌菌株进行了评估，并显示出显着的抗真菌活性，其效力比氟康唑高约37倍。 图形概要

  DOI：

  10.1007/s11696-017-0298-1

文献信息

• Structure-Activity Relationship (SAR) Studies on Oxazolidinone Antibacterial Agents. 2. Relationship between Lipophilicity and Antibacterial Activity in 5-Thiocarbonyl Oxazolidinones.
  作者：Ryukou TOKUYAMA、Yoshiei TAKAHASHI、Yayoi TOMITA、Masatoshi TSUBOUCHI、Toshihiko YOSHIDA、Nobuhiko IWASAKI、Noriyuki KADO、Eiichi OKEZAKI、Osamu NAGATA

  DOI：10.1248/cpb.49.353

  日期：——

  5-Thiourea and 5-dithiocarbamate oxazolidinones were synthesized as a continuation of research on 5-thiocarbonyl oxazolidinone antibacterial agents considering the hydrophobic parameters of the molecule. The structure-activity relationship (SAR) study revealed that the antibacterial activity on 5-thiocarbonyl oxazolidinones was significantly affected by the lipophilicity, especially the calculated

  考虑到分子的疏水性参数，对5-硫代羰基恶唑烷酮抗菌剂的研究继续进行，合成了5-硫脲和5-二硫代氨基甲酸酯恶唑烷酮。结构-活性关系（SAR）研究表明，亲脂性显着影响对5-硫代羰基恶唑烷酮的抗菌活性，尤其是计算出的log P值以及5-亲水（或疏水）取代基与疏水（或亲水）之间的平衡苯环上的取代基。发现一些5-硫代羰基恶唑烷酮对革兰氏阳性细菌具有良好的体外抗菌活性，包括耐甲氧西林的金黄色葡萄球菌（MRSA）和耐万古霉素的肠球菌（VRE）。
• [EN] OXAZOLIDINONES CONTAINING A SULFONIMID GROUP AS ANTIBIOTICS<br/>[FR] OXAZOLIDINONES CONTENANT UN GROUPE SULFONIMIDE EN TANT QU'ANTIBIOTIQUE
  申请人：ASTRAZENECA AB

  公开号：WO2002081470A1

  公开（公告）日：2002-10-17

  Compounds of the formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof (I) wherein, for example, HET is an N-linked 5-membered, fully or partially unsaturated heterocyclic ring, or an N-linked 6-membered di-hydro-heteroaryl ring; andQ is, for example, Q1 or Q2 : Q1 Q2 wherein R?2 and R3¿ are independently hydrogen or fluoro;T is selected, for example, from a group of the formula (TA1) or (TA2) :- (TA1) (TA2)wherein, for example, X¿1m? is O= and X2m is R2s-(E)ms-N-;wherein E is an electron withdrawing group, for example, -SO2- or -CO-; and, for example, R2s is hydrogen or (1-6C)alkyl; are useful as pharmaceutical 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，例如，HET是N-连接的5元环，完全或部分不饱和的杂环，或N-连接的6元双氢杂环基；而Q是，例如，Q1或Q2：Q1 Q2，其中R?2和R3¿独立地是氢或氟；T从公式（TA1）或（TA2）的一组中选择，例如：-（TA1）（TA2）其中，例如，X¿1m？是O=，而X2m是R2s-（E）ms-N-；其中E是电子提取基团，例如-SO2-或-CO-；例如，R2s是氢或（1-6C）烷基；它们是有用的药物；并且描述了其制造过程和含有它们的制药组合物。
• Substituted oxazine and thiazine oxazolidinone antimicrobials
  申请人：Pharmacia & Upjohn Company

  公开号：US05880118A1

  公开（公告）日：1999-03-09

  A compound of the Formula I: ##STR1## or pharmaceutically acceptable salts thereof wherein X, R, R.sup.1, R.sup.2, R.sup.3 and n are as defined in the disclosure. The oxazine and thiazine oxazolidinone derivatives are useful antimicrobial agents effective against a number of human and veterinary pathogens, including gram-positive aerobic bacteria such as multiply-resistant staphylococci, streptococci, and enterococci as well as anaerobic organisms such as Bacteroides spp. and Clostridia spp. species, and acid-fast organisms such as Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium spp.

  化合物I的公式：##STR1##或其药学上可接受的盐，其中X，R，R.sup.1，R.sup.2，R.sup.3和n如所披露的定义。这些噁唑啉和噻唑噁唑烷衍生物是有效的抗微生物剂，可用于治疗多种人类和兽医病原体，包括革兰氏阳性的厌氧菌，如耐药性葡萄球菌，链球菌和肠球菌，以及拟杆菌属和梭菌属等厌氧菌和酸性快速生长菌，如结核分枝杆菌，埃及分枝杆菌和分枝杆菌属。
• Novel linezolid-based oxazolidinones as potent anticandidiasis and antitubercular agents
  作者：Shaik Faazil、M. Shaheer Malik、Saleh A. Ahmed、Reem I. Alsantali、Poornachandra Yedla、Meshari A. Alsharif、Iqbal N. Shaikh、Ahmed Kamal

  DOI：10.1016/j.bioorg.2022.105869

  日期：2022.9

  Oxazolidinones are well-known antibacterial agents, with few investigations reported to exploit their antifungal properties. Herein, we report the design and synthesis of a series of linezolid-based oxazolidinones as potent anticandidiasis and antitubercular agents. Studies revealed that two of the novel oxazolidinones 2 and 3a exhibited excellent anticandidiasis activity against different Candida fungus

  由于病态的共同发病机制和免疫功能低下患者的增加，对新的抗真菌和抗结核药物的探索是当务之急。前进的方法之一是探索和重新利用已建立的药效团以用于所需的应用。恶唑烷酮是众所周知的抗菌剂，很少有研究报道利用它们的抗真菌特性。在此，我们报告了一系列基于利奈唑胺的恶唑烷酮类药物作为有效的抗念珠菌病和抗结核药物的设计和合成。研究表明，两种新型恶唑烷酮2和3a对不同的念珠菌表现出优异的抗念珠菌病活性真菌菌株，优于标准药物。机理和对接研究表明，恶唑烷酮类是麦角甾醇生物合成途径的更好抑制剂，比所使用的对照组更好。此外，恶唑烷酮2和3a对M. tuberculosis H 37 Rv也表现出显着的抑制活性，MIC 值分别为 1 和 2 μg/ml。计算研究证明了化合物与转录调节阻遏蛋白的结合，分子动力学模拟加强了这一点。药效团建模实验验证了两种靶蛋白的分子对接结果。
• THIOCARBAMIC ACID DERIVATIVES
  申请人：HOKURIKU SEIYAKU CO., LTD.

  公开号：EP1130016A1

  公开（公告）日：2001-09-05

  Thiocarbamic acid derivatives represented by the following general formula or salts thereof which are useful as antibacterial agents: wherein R1 represents an alkyl group which may be substituted, or a cycloalkyl group which may be substituted; and R2, R3, and R4 independently represent hydrogen atom, a halogen atom, an alkyl group which may be substituted, an alkogyl group which may be substituted, an amino group which may be substituted, an alkanoyl group which may be substituted, a cycloalkyloxy group which has a heteroatom as a ring constituting atom and which may be substituted, or a saturated heterocyclic group which may be substituted; or any two of R2, R3, and R4 may bind to each other to form, together with the benzene ring, a condensed hydrocarbon ring which may be substituted.

  由以下通式代表的可用作抗菌剂的硫代氨基甲酸衍生物或其盐： 其中 R1 代表可被取代的烷基，或可被取代的环烷基；R2、R3 和 R4 独立地代表氢原子、卤素原子、可被取代的烷基、可被取代的烷酰基、可被取代的氨基、可被取代的烷酰基、具有杂原子作为成环原子且可被取代的环烷氧基，或可被取代的饱和杂环基；或 R2、R3 和 R4 中的任意两个可相互结合，与苯环一起形成一个可被取代的缩合烃环。