(S)-N-[[3-[3-fluoro-4-(1,1-dioxothiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

• 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: (S)-N-[[3-[3-fluoro-4-(1,1-dioxothiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
• 英文别名: (S)-N-((3-(4-(1,1-dioxidothiomorpholino)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide；N-[[(5S)-3-[4-(1,1-dioxo-1,4-thiazinan-4-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide
• 化学式: C₁₆H₂₀FN₃O₅S
• 分子量: 385.416
• InChiKey: UYMQTPUEEPRWLS-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  26
• 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：
  104
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  sutezolid 在 四氧化锇 、 N-甲基吗啉氧化物 作用下， 以 水 、 丙酮 、 叔丁醇 为溶剂， 反应 16.0h， 以73%的产率得到(S)-N-[[3-[3-fluoro-4-(1,1-dioxothiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
  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

文献信息

• Substituted oxazine and thiazine oxazolidinone antimicrobials
  申请人：Pharmacia & Upjohn Company

  公开号：US05688792A1

  公开（公告）日：1997-11-18

  A compound of structural Formula I: ##STR1## or pharmaceutically acceptable salts thereof wherein: X is O, S, SO, SO.sub.2, SNR.sup.10 or S(O)NR.sup.10 ; R is (a) hydrogen, (b) C.sub.1 -C.sub.8 alkyl optionally substituted with one or more of the following: F, Cl, hydroxy, C.sub.1 -C.sub.8 alkoxy, C.sub.1 -C.sub.8 acyloxy or --O--CH.sub.2 --Ph, (c) C.sub.3 -C.sub.6 cycloalkyl, (d) amino, (e) C.sub.1 -C.sub.8 alkylamino, (f) C.sub.1 -C.sub.8 dialkylamino or (g) C.sub.1 -C.sub.8 alkoxy; R.sup.1 is H, except when X is O then R.sup.1 can be H, CH.sub.3, CN, CO.sub.2 H, CO.sub.2 R or (CH.sub.2).sub.m R.sup.11 (m is 1 or 2); R.sup.2 is independently H, F or Cl; R.sup.3 is H except when X is O and R.sup.1 is CH.sub.3 then R.sup.3 can be H or CH.sub.3 ; R.sup.10 is independently H, C.sub.1 -C.sub.4 alkyl (optionally substituted with chloro, fluoro, hydroxy, C.sub.1 -C.sub.8 alkoxy, amino, C.sub.1 -C.sub.8 alkylamino, or C.sub.1 -C.sub.8 dialkylamino) or p-toluenesulfonyl; R.sup.11 is hydrogen, OH, OR, OCOR, NH.sub.2, NHCOR or N(R.sup.10).sub.2 ; and n is 0, 1 or 2. 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.

  结构式I的化合物：##STR1## 或其药用可接受的盐，其中：X为O、S、SO、SO.sub.2、SNR.sup.10或S(O)NR.sup.10；R为(a)氢、(b)C.sub.1-C.sub.8烷基，可选择地取代为以下一种或多种：F、Cl、羟基、C.sub.1-C.sub.8烷氧基、C.sub.1-C.sub.8酰氧基或--O--CH.sub.2--Ph，(c)C.sub.3-C.sub.6环烷基，(d)氨基，(e)C.sub.1-C.sub.8烷基氨基，(f)C.sub.1-C.sub.8二烷基氨基或(g)C.sub.1-C.sub.8烷氧基；R.sup.1为H，但当X为O时，R.sup.1可以是H、CH.sub.3、CN、CO.sub.2 H、CO.sub.2 R或(CH.sub.2).sub.mR.sup.11（m为1或2）；R.sup.2独立地为H、F或Cl；R.sup.3为H，但当X为O且R.sup.1为CH.sub.3时，R.sup.3可以是H或CH.sub.3；R.sup.10独立地为H、C.sub.1-C.sub.4烷基（可选择地取代为氯、氟、羟基、C.sub.1-C.sub.8烷氧基、氨基、C.sub.1-C.sub.8烷基氨基或C.sub.1-C.sub.8二烷基氨基）或对甲苯磺酰基；R.sup.11为氢、OH、OR、OCOR、NH.sub.2、NHCOR或N(R.sup.10).sub.2；n为0、1或2。噁嗪和噻嗪噁唑烷酮衍生物对多种人类和兽医病原体具有抗菌作用，包括革兰氏阳性厌氧细菌，如多重耐药葡萄球菌、链球菌和肠球菌，以及厌氧生物，如Bacteroides属和Clostridia属物种，以及耐酸生物，如结核分枝杆菌、鸟型分枝杆菌和分枝杆菌属。
• Solution composition of an oxazolidinone antibiotic drug having enhanced drug loading
  申请人：——

  公开号：US20020068720A1

  公开（公告）日：2002-06-06

  There is provided a pharmaceutical composition for therapeutic or prophylactic administration to a subject having an infective disease or condition or at risk thereof. The composition comprises an aqueous carrier having in solution therein (a) an oxazolidinone antimicrobial drug, for example linezolid, in a therapeutically or prophylactically effective drug concentration that is above the practical limit of solubility of the drug in a substantially isotonic aqueous solution at a physiologically compatible pH, and (b) a pharmaceutically acceptable cyclodextrin compound in a concentration sufficient to maintain the drug in solution at such a drug concentration. The composition is particularly useful for intravenous delivery of the drug.

  本发明提供了一种药物组合物，用于对患有感染性疾病或病症或有感染风险的受试者进行治疗或预防用药。该组合物包括一种水性载体，其溶液中含有(a)一种噁唑烷酮类抗菌药物，例如利奈唑胺，其治疗或预防有效药物浓度高于该药物在生理相容 pH 值的基本等渗水溶液中的实际溶解极限；(b)一种药学上可接受的环糊精化合物，其浓度足以使该药物在溶液中保持这样的药物浓度。该组合物特别适用于静脉注射给药。
• Preservative free ophthalmic oxazolidinone antibiotic drug delivery systems
  申请人：——

  公开号：US20030027790A1

  公开（公告）日：2003-02-06

  There is provided a pharmaceutical preservative free composition suitable for topical administration to an eye, the composition comprising (a) an oxazolidinone antimicrobial drug, for example linezolid, in a therapeutically or prophylactically effective drug concentration that is above the practical limit of solubility of the drug in a substantially isotonic aqueous solution at a physiologically compatible pH, and (b) a pharmaceutically acceptable cyclodextrin compound in a concentration sufficient to maintain the drug-in solution at such a drug concentration. The composition is particularly useful for the treatment and/or prevention of eye infections due to gram positive bacteria.

  本发明提供了一种适用于眼部局部用药的不含防腐剂的药用组合物，该组合物包括：(a) 一种噁唑烷酮类抗菌药物，例如利奈唑胺，其治疗或预防有效药物浓度高于该药物在生理兼容 pH 值下的基本等渗水溶液中的实际溶解极限；(b) 一种药学上可接受的环糊精化合物，其浓度足以将药物溶液维持在这样的药物浓度。该组合物特别适用于治疗和/或预防革兰氏阳性菌引起的眼部感染。
• SUBSTITUTED OXAZINE AND THIAZINE OXAZOLIDINONE ANTIMICROBIALS
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP0717738B1

  公开（公告）日：1999-10-20
• AMINOARYL OXAZOLIDINONE N-OXIDES
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP1019385B1

  公开（公告）日：2004-01-14