(3-氟-4-硫代吗啉苯基)氨基甲酸苄酯 | 168828-71-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻嗪类
• 中文名称: (3-氟-4-硫代吗啉苯基)氨基甲酸苄酯
• 英文名称: 4-<2-fluoro-4-<(benzyloxycarbonyl)amino>phenyl>thiomorpholine
• 英文别名: N-carbobenzoxy-3-fluoro-4-(4-thiomorpholinyl)aniline；(3-fluoro-4-thiomorpholin-4-ylphenyl)carbamic acid benzyl ester；4-[2-fluoro-4-(benzyloxycarbonyl)aminophenyl]thiomorpholine；benzyl (3-fluoro-4-thiomorpholinophenyl)carbamate；[3-fluoro-4-(4-thiomorpholinyl)phenyl]carbamic acid, phenylmethyl ester；benzyl N-[3-fluoro-4-(thiomorpholin-4-yl)phenyl]carbamate；benzyl N-(3-fluoro-4-thiomorpholin-4-ylphenyl)carbamate
• CAS: 168828-71-5
• 化学式: C₁₈H₁₉FN₂O₂S
• 分子量: 346.425
• InChiKey: IFTVWPQLBCYBPN-UHFFFAOYSA-N

物化性质

• 熔点：
  128-130 °C
• 沸点：
  476.5±45.0 °C(Predicted)
• 密度：
  1.304±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  66.9
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  (3-氟-4-硫代吗啉苯基)氨基甲酸苄酯 在 吡啶 、 正丁基锂 、 sodium azide 、 水 、 三乙胺 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 20.0h， 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 palladium on activated charcoal 、 氢气 、 碳酸氢钠 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 、 丙酮 、 乙腈 为溶剂， 反应 27.0h， 生成 (3-氟-4-硫代吗啉苯基)氨基甲酸苄酯
  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
• 作为试剂：
  描述：

  (R)-1-chloro-3-{[(4-chlorophenyl)methylene]amino}propan-2-ol 、 (3-氟-4-硫代吗啉苯基)氨基甲酸苄酯 在 (3-氟-4-硫代吗啉苯基)氨基甲酸苄酯 作用下， 以99的产率得到(5S)-5-{[((E)-4-chlorobenzylidene)amino]methyl}-3-(3-fluoro-4-thiomorpholin-4-ylphenyl)-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Combination Therapy for Tuberculosis

  摘要：

  本发明涉及治疗结核病的方法，包括多药耐药性和潜伏结核病。更具体地，本发明涉及一种治疗哺乳动物结核病的方法，包括向需要治疗的哺乳动物中投与化合物(I)、(S)-N-[[3-[3-氟-4-(4-硫代吗啉基)苯基]-2-氧代-5-噁唑烷基]甲基]乙酰胺或其药学上可接受的盐，以及至少两种对治疗结核病有用的药剂。本发明还涉及一种药物组合物，包括治疗上述结核病的治疗剂量的化合物(I)或其药学上可接受的盐或溶剂、至少一种治疗结核病有用的治疗剂量的药剂和一种或多种药学上可接受的载体或载体。

  公开号：

  US20160220578A1

文献信息

• Syntheses and antibacterial activity studies of new oxazolidinones from nitroso Diels–Alder chemistry
  作者：Shanshan Yan、Marvin J. Miller、Timothy A. Wencewicz、Ute Möllmann

  DOI：10.1016/j.bmcl.2009.10.018

  日期：2010.2

  of novel oxazolidinone antibiotics having [2.2.1] and [2.2.2] bicyclic oxazine moieties at the C-5 side chain of the A-ring was synthesized by nitroso Diels–Alder reactions, from three linezolid analogs containing morpholine, piperazine and thiomorpholine, respectively, as the C-ring components. Subsequent N–O bond cleavage generated oxazolidinones with 4-amino cyclo-2-en-1-ol substituents. The in vitro

  通过亚硝基 Diels-Alder 反应，从含有吗啉、哌嗪的三种利奈唑胺类似物合成了一系列在 A 环 C-5 侧链具有 [2.2.1] 和 [2.2.2] 双环恶嗪部分的新型恶唑烷酮抗生素和硫代吗啉，分别作为 C 环组分。随后的 N-O 键断裂产生了带有 4-氨基环-2-烯-1-醇取代基的恶唑烷酮。评价了这些恶唑烷酮类似物的体外抗菌活性。
• 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。
• Spectroscopic identification of intermediates and final products of the chiral pool synthesis of sutezolid
  作者：Katarzyna Michalska、Kornelia Lewandowska、Mikołaj Mizera、Wojciech Bocian、Barbara Pałys、Judyta Cielecka-Piontek

  DOI：10.1016/j.molstruc.2020.128396

  日期：2020.10

  currently in clinical trials to determine its safety and efficacy towards highly drug-resistant tuberculosis. The aim of the study was the spectroscopic identification of selected key intermediate products of the chiral pool synthesis of sutezolid: (S1) (4-(2-fluoro-4-nitrophenyl)thiomorpholine), (S2) 4-[2-fluoro-4-(benzyloxycarbonyl)aminophenyl] thiomorpholine, (S4) (R)-[[3-[3-fluoro-4-(4-thiomorpholinyl)

  摘要 Sutezolid 是一种新型恶唑烷酮衍生物，目前正在进行临床试验，以确定其对高度耐药结核病的安全性和有效性。本研究的目的是对 sutezolid 手性池合成的选定关键中间产物进行光谱鉴定：(S1) (4-(2-fluoro-4-nitrophenyl)thiomorpholine), (S2) 4-[2-fluoro- 4-(苄氧羰基)氨基苯基]硫代吗啉，(S4)(R)-[[3-[3-氟-4-(4-硫代吗啉基)苯基]-2-氧代-5-恶唑烷基]甲基]-对甲苯磺酸盐， (S5) (R)-[[3-(3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]azide，以及 (S6) sutezolid，最终合成产物. 光谱鉴定基于红外光谱分析（FT-IR）和拉曼散射。这部分分析得到了基于密度泛函理论 (DFT) 的量子化学计算的支持，该计算利用
• 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。
• Structure-Activity Relationship (SAR) Studies on Oxazolidinone Antibacterial Agents. 1. Conversion of 5-Substituent on Oxazolidinone.
  作者：Ryukou TOKUYAMA、Yoshiei TAKAHASHI、Yayoi TOMITA、Tomio SUZUKI、Toshihiko YOSHIDA、Nobuhiko IWASAKI、Noriyuki KADO、Eiichi OKEZAKI、Osamu NAGATA

  DOI：10.1248/cpb.49.347

  日期：——

  A structure-activity relationship (SAR) study on 5-substituted oxazolidinones as an antibacterial agent is described. The oxazolidinones, of which 5-acetylaminomethyl moiety was converted into other functions, were prepared and evaluated for antibacterial activity. Elongation of the methylene chain (8) and conversion of the acetamido moiety into guanidino moiety (12) decreased the antibacterial activity. The replacement of carbonyl oxygen (=O) by thiocarbonyl sulfur (=S) enhanced in vitro antibacterial activity. Especially, compound 16, which had the 5-thiourea group, showed 4-8 stronger in vitro activity than linezolid. Our SAR study revealed that the antibacterial activity was greatly affected by the conversion of 5-substituent.

  描述了一项关于作为抗菌剂的5-取代恶唑烷酮的构效关系（SAR）研究。通过将5-乙酰氨基甲基部分转化为其他功能基团，制备并评价了这些恶唑烷酮的抗菌活性。延长甲撑链（8）和将乙酰氨基部分转化为胍基部分（12）降低了抗菌活性。用硫代羰基硫（=S）取代羰基氧（=O）增强了体外抗菌活性。特别是化合物16，具有5-硫脲基团，其体外活性比利奈唑胺强4-8倍。我们的SAR研究表明，5-取代基的转化对抗菌活性有很大影响。