PNU-101603 | 168828-60-2

• 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: PNU-101603
• 英文别名: N-[[(5S)-3-[3-fluoro-4-(1-oxido-4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide；(S)-N-((3-(3-fluoro-4-(1-oxidothiomorpholino)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide；N-[[(5S)-3-[3-fluoro-4-(1-oxo-1,4-thiazinan-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide
• CAS: 168828-60-2
• 化学式: C₁₆H₂₀FN₃O₄S
• 分子量: 369.417
• InChiKey: WNRIDZUNMXATND-ZDUSSCGKSA-N

物化性质

• 溶解度：
  DMSO：100 mg/mL（270.70 mM；需要超声波）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 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：
  98.2
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 储存条件：
  室温

制备方法与用途

PNU-101603是Sutezolid（HY-10392）的代谢产物，对结核分枝杆菌（MTB）表现出优异的活性。

反应信息

• 作为反应物：
  描述：

  acetone hexane 、 PNU-101603 在 PPA 作用下， 以 甲醇 、 水 为溶剂， 生成 N-({(5S)-3-[3-Fluoro-4-(1-imino-1-oxido-1λ4,4-thiazinan-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide
  参考文献：
  名称：

  Oxazolidinones having a sulfoximine functionality

  摘要：

  本发明提供了一种式子为I1的化合物，该化合物具有对革兰氏阳性和革兰氏阴性细菌具有强效活性。

  公开号：

  US20010046987A1
• 作为产物：
  描述：

  sutezolid 在 sodium periodate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以95%的产率得到PNU-101603
  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

• [EN] SUBSTITUTED PHENYLOXAZOLIDINONES FOR ANTIMICROBIAL THERAPY<br/>[FR] PHENYL-OXAZOLIDINONES SUBSTITUÉES POUR LA THÉRAPIE ANTIMICROBIENNE
  申请人：THE GLOBAL ALLIANCE FOR TB DRUG DEV INC

  公开号：WO2017015106A1

  公开（公告）日：2017-01-26

  The present invention relates to novel oxazolidinones (Formula I): or a pharmaceutically acceptable salt having ring A characterized by N-containing monocyclic, bicyclic or spirocyclic substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

  本发明涉及新型噁唑烷酮（化学式I）：或具有由含氮的单环、双环或螺环取代基特征的环A的药用盐，以及其制备方法，以及作为用于治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用或与其他抗感染治疗结合使用。
• Antimicrobial dihydrothiazine and dihydrothiopyran oxazolidinones
  申请人：——

  公开号：US20030232812A1

  公开（公告）日：2003-12-18

  The present invention provides a compound of formula I 1 or a pharmaceutically acceptable salt thereof wherein A, X, Y, Z, R 2 , R 3 , R 4 , R 5 , and R 6 are as defined herein. The compounds of formula I are useful as antimicrobials against a number of human and veterinary pathogens.

  本发明提供了一种具有化学式I1的化合物或其药用可接受的盐，其中A、X、Y、Z、R2、R3、R4、R5和R6如本文所定义。化合物I的公式对抗多种人类和兽医病原体具有抗微生物作用。
• [EN] ANTIMICROBIAL DIHYDROTHIAZINE AND DIHYDROTHIOPYRAN OXAZOLIDINONES<br/>[FR] ANTIMICROBIENS A BASE D'OXAZOLIDINONES DE DIHYDROTHIAZINE ET DE DIHYDROTHIOPYRANE
  申请人：UPJOHN CO

  公开号：WO2003062231A1

  公开（公告）日：2003-07-31

  The present invention provides a compound of formula (I): Or a pharmaceutically acceptable salt thereof wherein A, X, Y, Z, R2, R3, R4, R5, and R6 are as defined herein. The compounds of formula (I) are useful as antimicrobials against a number of human and veterinary pathogens.

  本发明提供了式(I)的化合物：或其药学上可接受的盐，其中A、X、Y、Z、R2、R3、R4、R5和R6如本文所定义。式(I)的化合物对许多人类和兽医病原体具有抗微生物作用。
• 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。
• SUBSTITUTED PHENYLOXAZOLIDINONES FOR ANTIMICROBIAL THERAPY
  申请人：The Global Alliance for TB Drug Development, Inc.

  公开号：EP3932917A2

  公开（公告）日：2022-01-05

  The present invention relates to novel oxazolidinones (Formula I): or a pharmaceutically acceptable salt having ring A characterized by N-containing monocyclic, bicyclic or spirocyclic substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

  本发明涉及新型噁唑烷酮（式 I）： 或具有以含 N 的单环、双环或螺环取代基为特征的环 A 的药学上可接受的盐，涉及它们的制备，以及它们作为治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用，也可以与其他抗感染治疗药物联合使用。