Toluene-4-sulfonic acid (R)-3-(3-fluoro-4-thiomorpholin-4-yl-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester | 168828-73-7

• 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: Toluene-4-sulfonic acid (R)-3-(3-fluoro-4-thiomorpholin-4-yl-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester
• 英文别名: (R)-(3-(3-Fluoro-4-thiomorpholinophenyl)-2-oxooxazolidin-5-YL)methyl 4-methylbenzenesulfonate；[(5R)-3-(3-fluoro-4-thiomorpholin-4-ylphenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl 4-methylbenzenesulfonate
• CAS: 168828-73-7
• 化学式: C₂₁H₂₃FN₂O₅S₂
• 分子量: 466.554
• InChiKey: JLDPJKVAJJNZGJ-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  8

安全信息

• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  Toluene-4-sulfonic acid (R)-3-(3-fluoro-4-thiomorpholin-4-yl-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester 在 吡啶 、 sodium azide 、 水 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 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 W-2 Raney nickel 吡啶 、 正丁基锂 、 氢气 、 碳酸氢钠 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， -78.0~25.0 ℃ 、275.79 kPa 条件下， 反应 34.5h， 生成 Toluene-4-sulfonic acid (R)-3-(3-fluoro-4-thiomorpholin-4-yl-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester
  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##或其药学上可接受的盐，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，可选地取代以下一种或多种：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，除非X为O，然后R.sup.1可以是H，CH.sub.3，CN，CO.sub.2H，CO.sub.2R或（CH.sub.2）.sub.mR.sup.11（m为1或2）;R.sup.2是独立的H，F或Cl;R.sup.3为H，除非X为O且R.sup.1为CH.sub.3，然后R.sup.3可以是H或CH.sub.3;R.sup.10是独立的H，C.sub.1-C.sub.4烷基（可选地取代氯，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;且n为0、1或2。这些噁唑啉和噻唑噁唑烷衍生物是有用的抗微生物药物，对多种人类和兽医病原体有效，包括革兰阳性的好氧菌，如耐多种抗生素的葡萄球菌，链球菌和肠球菌，以及厌氧菌，如Bacteroides spp.和Clostridia spp.菌种，以及酸性快速生长的菌，如结核分枝杆菌，鸟型分枝杆菌和分枝杆菌属。
• Identification of a Novel Oxazolidinone (U-100480) with Potent Antimycobacterial Activity
  作者：Michael R. Barbachyn、Douglas K. Hutchinson、Steven J. Brickner、Michael H. Cynamon、James O. Kilburn、Sally P. Klemens、Suzanne E. Glickman、Kevin C. Grega、Susan K. Hendges、Dana S. Toops、Charles W. Ford、Gary E. Zurenko

  DOI：10.1021/jm950956y

  日期：1996.1.1

  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.