左氧氟沙星杂质L | 110548-07-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 左氧氟沙星杂质L
• 中文别名: (R)-氧氟沙星羧酸；左氧氟沙星杂质8
• 英文名称: (R)-(+)-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid
• 英文别名: (+)-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido<1,2,3-de><1,4>benzoxazine-6-carboxylic acid；(+)-9,10-difluoro-3(R)-methyl-7-oxo-2,3-dihydro-7H-pyrido<1,2,3-de>-1,4-benzoxazine-6-carboxylic acid；9,10-difluoro-3,7-dihydro-3-methyl-7-oxo-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid；[R]-(+)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid；(R)-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid；(+)-9,10-difluoro-3(R)-methyl-7-oxo-2,3-dihydro-7H-pyrido(1,2,3-de)-1,4-benzoxazine-6-carboxylic acid；Ofloxacin Q acid, (R)-；(2R)-6,7-difluoro-2-methyl-10-oxo-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carboxylic acid
• CAS: 110548-07-7
• 化学式: C₁₃H₉F₂NO₄
• 分子量: 281.216
• InChiKey: NVKWWNNJFKZNJO-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  左氧氟沙星杂质L 在 N-甲基吗啉 、 盐酸 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 34.0h， 生成
  参考文献：
  名称：

  Syntheses of quinolone hydrochloride enantiomers from synthons (R)- and (S)-2-methylpiperazine

  摘要：

  A series of R and S enantiomers of 7-(3-methylpiperazin-l-yl) quinolone derivatives were synthesized from (R)- and (S)tert-butyl 2-methylpiperazine-l-carboxylate and tested for their antibacterial activities on 14 kinds of bacteria. Although no distinct difference in in vitro antibacterial activities was observed, 2-64-fold difference between R and S enantiomers was observed in approximately 52% of cases. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.01.032
• 作为产物：
  描述：

  (-)-ethyl 2-<<<(R)-1-hydroxyprop-2-yl>amino>methylene>-3-oxo-3-(2,3,4,5-tetrafluorophenyl)propionate 在 氢氧化钾 、 sodium hydride 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 5.0h， 生成 左氧氟沙星杂质L
  参考文献：
  名称：

  手性DNA促旋酶抑制剂。2. 9-氟-3-甲基-10-（4-甲基-1-哌嗪基）-7-氧代-2,3-二氢-7H-吡啶基[1,2,3]的对映异构体的不对称合成及其生物活性-[de] -1,4-苯并恶嗪-6-羧酸（氧氟沙星）。

  摘要：

  已经设计了一种短而有效的合成方法，以氧氟沙星喹诺酮类抗菌剂的两种光学对映体为起始，从（R）-和（S）-丙氨醇开始合成。在体外测试产品对一系列细菌的影响，并在包含来自不同细菌物种的纯化DNA促旋酶的测定系统中进行测试，结果表明S-（-）对映异构体的活性更高。

  DOI：

  10.1021/jm00395a017

文献信息

• 7-Azetidinylquinolones as Antibacterial Agents. 3. Synthesis, Properties and Structure-Activity Relationships of the Stereoisomers Containing a 7-(3-Amino-2-methyl-1-azetidinyl) Moiety
  作者：Jordi Frigola、David Vano、Antoni Torrens、Angels Gomez-Gomar、Edmundo Ortega、Santiago Garcia-Granda

  DOI：10.1021/jm00007a017

  日期：1995.3

  de]-1,4-benzoxazine-6-carboxylic acids was synthesized to study the effect of the azetidine moiety on tricyclic quinolone antibacterial agents. A series of amino acid prodrugs of chiral naphthyridines 24a and 24b and quinolone 33a (cetefloxacin) was prepared and evaluated for antibacterial activity, solubility, and pharmacokinetic behavior. The absolute configuration of the new azetidinylquinolones

  一系列立体化学纯的7-（3-氨基-2-甲基-1-氮杂环丁烷基）-1,4-二氢-6-氟-4-氧代喹啉-和-1,8-萘啶-3-羧酸制备了位于1、5和8位的取代基，以确定手性相对于外消旋混合物的效价和体内功效的影响（第2部分，参见：J. Med.Chem。1994，37， 4195-4210）。一系列手性9-氟-2,3-二氢-3-甲基-7-氧-10-（取代的1-氮杂环丁烷基）-7H-吡啶[1,2,3-de] -1,4-苯并恶嗪合成-6-羧酸以研究氮杂环丁烷部分对三环喹诺酮抗菌剂的作用。制备了一系列手性萘啶24a和24b以及喹诺酮33a（cetefloxacin）的氨基酸前药，并评估了其抗菌活性，溶解度和药代动力学行为。通过对拆分的氮杂环丁醇（15）和化合物25a（E-4767）的一种非对映异构盐进行X射线分析，可以确定新的氮杂环丁烷基喹诺酮类化合物的绝对构型，该化合物在体外和体内的总体情况最佳。
• Design, Synthesis, <i>In Vitro</i> Antimicrobial, Antioxidant Evaluation, and Molecular Docking Study of Novel Benzimidazole and Benzoxazole Derivatives
  作者：Bharat B. Kashid、Anil A. Ghanwat、Vijay M. Khedkar、Balasaheb B. Dongare、Mubarak H. Shaikh、Prathmesh P. Deshpande、Yogesh B. Wakchaure

  DOI：10.1002/jhet.3467

  日期：2019.3

  2‐substituted benzimidazole and benzoxazole derivatives as a potential antimicrobial and antioxidant agent were synthesized via coupling of N‐methyl‐o‐phenylenediamine or 2‐amino‐phenol with aromatic aldehyde and acid in the presence of polyphosphoric acid as an efficient catalyst as well as solvent by conventional method in short reaction times with excellent yield. The newly synthesized benzimidazole and benzoxazole

  在多磷酸存在下，通过将N-甲基邻苯二胺或2-氨基苯酚与芳族醛和酸偶合，合成了一系列新型的2-取代的苯并咪唑和苯并恶唑衍生物，作为潜在的抗菌剂和抗氧化剂。通过常规方法在短反应时间内以优异的收率得到催化剂和溶剂。对新合成的苯并咪唑和苯并恶唑衍生物的抗微生物和抗氧化活性进行了评估，与标准药物相比，表现出优异至良好的活性。此外，基于对微生物DNA促旋酶的分子对接的理论预测可以提供可能的作用机理的见解，并在观察到的抗菌活性与控制活性的特定热力学（键合和非键合）相互作用的结合亲和力之间建立联系。此外，对合成的化合物的吸收，分布，代谢和排泄特性进行了分析，并显示出潜在的特性，可作为良好的口服药物候选物。
• Optically active benzoxazines and bezothiazines and a process for their stereospecific preparation
  申请人：GIST-BROCADES N.V.

  公开号：EP0368410A3

  公开（公告）日：1990-09-05

  Optically active 7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazines and 7,8-difluoro-3,4-dihydro-2-methyl-2H-[1,4]benzoxazines and the corresponding benzothiazines of formula III, where, one of the substituents R1, R2, R3 and R4 is CH20H or -CH2Z, the remaining being hydrogen, X denotes fluoro, chloro, methyl or hydrogen, Y is oxygen or sulfur and Z is hydrogen, fluoro or protected hydroxyl are obtained as the stereochemically pure products of a stereospecific synthesis using a 3,4-difluoronitrobenzene substituted with a stereochemically pure 2-(1-hydroxyisopropoxy), 2-(2-hydrox-I ypropoxy), 2-(1-hydroxyisopropylthio) or 2-(2-hydroxypropylthio) substituent.The obtained compounds are suited for the production of optically active pyridobenzoxazines and pyridobenzothiazines, among which are useful antibacterial optically active quinolones, particularly (S)-(-)-ofloxacin.

  具有光学活性的7,8-二氟-3,4-二氢-3-甲基-2H-[1,4]苯并噁嗪和7,8-二氟-3,4-二氢-2-甲基-2H-[1,4]苯并噁嗪以及相应的式III的苯并噻嗪，其中R1、R2、R3和R4中的一个取代基是CH20H或-CH2Z，其余为氢，X代表氟、氯、甲基或氢，Y为氧或硫，Z为氢、氟或受保护的羟基，作为立体化学纯产品通过使用具有立体化学纯2-(1-羟基异丙氧基)、2-(2-羟基异丙氧基)、2-(1-羟基异丙基硫基)或2-(2-羟基丙硫基)取代基的3,4-二氟硝基苯进行立体特异性合成而获得。所得化合物适用于生产光学活性的吡啶苯并噁嗪和吡啶苯并噻嗪，其中包括有用的抗菌光学活性喹诺酮，特别是(S)-(-)-氧氟沙星。
• synthesis and antibacterial activities of optically active ofloxacin and its fluoromethyl derivative.
  作者：SHOHGO ATARASHI、SHUICHI YOKOHAMA、KEN-ICHI YAMAZAKI、KATSU-ICHI SAKANO、MASAZUMI IMAMURA、ISAO HAYAKAWA

  DOI：10.1248/cpb.35.1896

  日期：——

  Two optically active (100% enantiomeric excess) isomers (13a and 13b) of ofloxacin (1) [(±) -ofloxacin; DL-8280; (±) -9-fluoro-2, 3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl) -7-oxo-7H-pyrido [1, 2, 3-de] [1, 4] benzoxazine-6-carboxylic acid] and their fluoromethyl derivatives (14a and 14b) were prepared via their optically active intermediates resolved by use of high-performance liquid chromatography (HPLC). The isomers (13a and 13b) were also obtained efficiently by an alternative route via separation of the diastereoisomers (18, 19) prepared in the reaction of benzoxazine (17) with L-prolinyl chloride. The (-) -isomers of 1 and its fluoromethyl derivative (2) were approximately twice as active as the corresponding racemates, while the (+) -isomers were considerably less active than the racemates. The absolute configuration at the C3 position in the oxazine ring in a series of (-) -compounds (b) was confirmed by X-ray analysis of the hydrochloride of the (-) -benzoxazine derivative (15b) to be S.

  氧氟沙星（1）[(±) -ofloxacin; DL-8280；(±)-9-氟-2, 3-二氢-3-甲基-10- (4-甲基-1-哌嗪基) -7-氧代-7H-吡啶并[1, 2, 3-de] [1, 4] 苯并恶嗪-6-羧酸]及其氟甲基衍生物 (14a 和 14b)是通过使用高效液相色谱法 (HPLC) 解析其光学活性中间体而制备的。通过苯并恶嗪（17）与 L-脯氨酰氯反应制备的非对映异构体（18、19）的分离，也可以通过另一种途径有效地获得异构体（13a 和 13b）。1 的 (-) - 异构体及其氟甲基衍生物 (2) 的活性大约是相应外消旋体的两倍，而 (+) - 异构体的活性则大大低于外消旋体。通过对 (-) - 苯并恶嗪衍生物 (15b) 的盐酸盐进行 X 射线分析，证实了一系列 (-) - 化合物 (b) 中恶嗪环 C3 位置的绝对构型为 S。
• Drug efflux pump inhibitor
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1652839A2

  公开（公告）日：2006-05-03

  A medicament for preventive and/or therapeutic treatment of a microbial infection having an activity of eliminating resistance of a microorganism with acquired resistance to an antimicrobial agent, which comprises as an active ingredient a compound represented by the following general formula (I), a physiologically acceptable salt thereof, or a hydrate thereof: wherein R1 and R2 independently represent hydrogen atom, a halogen atom, carboxyl group and the like; J1 represents a 5- or 6-membered heteroaromatic ring; W1 represents -CH=CH-, -C≡C-, -CH2CH2- and the like; A1 represents phenylene group, pyridinediyl group, furandiyl group and the like; G1 represents oxygen atom, carbonyl group, ethynyl group and the like; p represents an integer of from 0 to 3; G2 represents phenylene group, furandiyl group, tetrahydrofurandiyl group and the like; G3 represents -CH2- or single bond; m and n represent an integer of 0 or 1; and Q1 represents an acidic group.

  一种用于预防和/或治疗微生物感染的药物，具有消除对抗菌剂产生抗药性的微生物的抗药性的活性，其活性成分包括下式（I）所代表的化合物、其生理上可接受的盐或其水合物： 其中 R1 和 R2 分别代表氢原子、卤素原子、羧基等；J1 代表 5 或 6 元杂芳环；W1 代表 -CH=CH-、-C≡C-、-CH2CH2- 等；A1 代表亚苯基、吡啶二基、呋喃二基等；G1 代表氧原子、羰基、乙炔基等；p 代表 0 至 3 的整数；G2 代表亚苯基、呋喃二基、四氢呋喃二基等；G3 代表 -CH2- 或单键；m 和 n 代表 0 或 1 的整数；以及 Q1 代表酸性基团。