R-(+)-9-fluoro-8-(4-hydroxypiperidin-1-yl)-5-methyl-6,7-dihydro-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid | 160961-35-3

• 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
• 英文名称: R-(+)-9-fluoro-8-(4-hydroxypiperidin-1-yl)-5-methyl-6,7-dihydro-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid
• 英文别名: (R)-(+)-nadifloxacin；R-(+)-nadifloxacin；(+)-nadifloxacin；R-(+)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid；(R)-nadifloxacin；(12R)-7-fluoro-8-(4-hydroxypiperidin-1-yl)-12-methyl-4-oxo-1-azatricyclo[7.3.1.05,13]trideca-2,5,7,9(13)-tetraene-3-carboxylic acid
• CAS: 160961-35-3
• 化学式: C₁₉H₂₁FN₂O₄
• 分子量: 360.385
• InChiKey: JYJTVFIEFKZWCJ-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  81.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  R-(+)-9-fluoro-8-(4-hydroxypiperidin-1-yl)-5-methyl-6,7-dihydro-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 2.0h， 生成 (R)-9-fluoro-8-(4-D-alaninyloxypiperidin-1-yl)-5-methyl-6,7-dihydro-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid methanesulfonate
  参考文献：
  名称：

  甲磺酸丙氧氟沙星旋光异构体及潜在杂质的合成、结构表征

  摘要：

  一种新型抗甲氧西林耐药金黄色葡萄球菌 (MRSA) 抗...

  DOI：

  10.1080/00397911.2022.2163403
• 作为产物：
  描述：

  那地沙星 在 Lux-cellulose-2 (cellulose tris(3-chloro-4-methyl phenyl carbamate)) column 作用下， 以 乙醇 、 正己烷 、 溶剂黄146 、 二乙胺 为溶剂， 生成 R-(+)-9-fluoro-8-(4-hydroxypiperidin-1-yl)-5-methyl-6,7-dihydro-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid 、 左氧那地沙星
  参考文献：
  名称：

  对映体分离所选氟喹诺酮类化合物的结构保留关系。

  摘要：

  氟喹诺酮类是具有不同化学功能的流行抗生素。它们大多数是具有一个手性中心的两性电解质。立体异构中心位于加替沙星（GFLX）的侧环或氧氟沙星（OFLX）的喹诺酮核心中。这两个两性氟喹诺酮类共有末端氨基。不寻常的纳地沙星（NFLX）是具有核心手性中心的酸性氟喹诺酮。由于GFLX，OFLX和NFLX之间的手性和功能差异，我们将这些对映异构体映射到结构-保留关系上。在筛选的流动相和纤维素三（3-氯-4-甲基苯基氨基甲酸酯）（Lux纤维素-2）固定相中研究了乙酸改性剂的量。已经应用了乙酸％和柱温的实验设计。拆分度和对映选择性与所研究对映异构体的结构特征有关。大量的酸（0.4％）最适合分离具有近氨基的侧手性（GFLX）或不具有基本功能的核心手性（NFLX），而少量（0.2％）最适合于具有远端氨基的核心手性中心氨基（OFLX）。除OFLX以外，温度对对映异构体的拆分和保留没有显着影响。对映保留解释了可能的

  DOI：

  10.1002/chir.22861

文献信息

• [EN] CRYSTALLINE FLUOROQUINOLONE ARGININE SALT FORM<br/>[FR] FORME CRISTALLINE DE SEL D'ARGININE DE FLUOROQUINOLONE
  申请人：WOCKHARDT LTD

  公开号：WO2003099815A1

  公开（公告）日：2003-12-04

  The invention relates to the new arginine salt forms of RS-(±)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid, S-(-)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid, R-(+)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid, a process for their preparation and pharmaceutical formulations which comprise those arginine salt forms as the active ingredient for its use in treating microbial infections.

  本发明涉及RS-(±)-9-氟-6,7-二氢-8-(4-羟基哌啶-1-基)-5-甲基-1-氧-1H,5H-苯并[i,j]喹啉-2-羧酸，S-(-)-9-氟-6,7-二氢-8-(4-羟基哌啶-1-基)-5-甲基-1-氧-1H,5H-苯并[i,j]喹啉-2-羧酸，R-(+)-9-氟-6,7-二氢-8-(4-羟基哌啶-1-基)-5-甲基-1-氧-1H,5H-苯并[i,j]喹啉-2-羧酸的新精氨酸盐形式，其制备方法和药物制剂，其中该精氨酸盐形式作为活性成分用于治疗微生物感染。
• CRYSTALLINE FLUOROQUINOLONE ARGININE SALT FORM
  申请人：WOCKHARDT LIMITED

  公开号：US20030225119A1

  公开（公告）日：2003-12-04

  The invention relates to the new arginine salt forms of RS-(±)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid, S-(−)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid, R-(+)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid, a process for their preparation and pharmaceutical formulations which comprise those arginine salt forms as the active ingredient for its use in treating microbial infections.

  本发明涉及RS-(±)-9-氟-6,7-二氢-8-(4-羟基哌啶-1-基)-5-甲基-1-氧代-1H,5H-苯并[i,j]喹啉-2-羧酸、S-(−)-9-氟-6,7-二氢-8-(4-羟基哌啶-1-基)-5-甲基-1-氧代-1H,5H-苯并[i,j]喹啉-2-羧酸、R-(+)-9-氟-6,7-二氢-8-(4-羟基哌啶-1-基)-5-甲基-1-氧代-1H,5H-苯并[i,j]喹啉-2-羧酸的新精氨酸盐形式，以及其制备方法和药物配方，其中该精氨酸盐形式作为活性成分用于治疗微生物感染。
• [EN] PURES-(-)-9-FLUORO-6,7-DIHYDRO-8-(4-HYDROXYPIPERIDIN-1-YL)-5-METHYL-1-OXO-1H,-5H-BENZO[I,J]QUINOLIZINE-2- CARBOXYLIC ACID L-ARGININE SALT TETRAHYDRATE AND A PROCESS FOR ITS PREPARATION<br/>[FR] SEL PUR TÉTRAHYDRATÉ DE L-ARGININE D'ACIDE S-(-)-9-FLUORO-6,7-DIHYDRO- 8-(4-HYDROXYPIPÉRIDIN-1-YL)-5-MÉTHYL-1-OXO-1H,-5H-BENZO[I,J]QUINOLIZINE- 2-CARBOXYLIQUE
  申请人：WOCKHARDT LTD

  公开号：WO2013046061A1

  公开（公告）日：2013-04-04

  Pure S-(-)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,- 5H-benzo[i,j]quinolizine-2-carboxylic acid L-arginine salt tetrahydrate and a process for its preparation is disclosed.

  本发明公开了纯S-(-)-9-氟-6,7-二氢-8-(4-羟基哌啶-1-基)-5-甲基-1-氧代-1H,-5H-苯并[i,j]喹啉-2-羧酸L-精氨酸盐四水合物及其制备方法。
• PURES-(-)-9-FLUORO-6,7-DIHYDRO-8-(4-HYDROXYPIPERIDIN-1-YL)-5-METHYL-1-OXO-1H,-5H-BENZO[I,J]QUINOLIZINE-2- CARBOXYLIC ACID L-ARGININE SALT TETRAHYDRATE AND A PROCESS FOR ITS PREPARATION
  申请人：Gangakhedkar Kiran Kumar

  公开号：US20140296280A1

  公开（公告）日：2014-10-02

  Pure S-(−)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,-5H-benzo[i,j]quinolizine-2-carboxylic acid L-arginine salt tetrahydrate and a process for its preparation is disclosed.

  本发明公开了纯的S-(−)-9-氟-6,7-二氢-8-(4-羟基哌啶-1-基)-5-甲基-1-氧代-1H,-5H-苯并[i,j]喹啉-2-羧酸L-精氨酸盐四水合物及其制备方法。
• Antibacterial chiral 8-(substituted piperidino)-benzo [i,j] quinolizines, processes, compositions and methods of treatment
  申请人：WOCKHARDT RESEARCH CENTER

  公开号：US20020165227A1

  公开（公告）日：2002-11-07

  The present invention relates to optically pure 8-(substituted piperidino)-benzo[i,j]quinolizines, their isomers, derivatives, salts, pseudopolymorphs, polymorphs prodrugs and hydrates thereof, to processes for their preparation, and to pharmaceutical compositions comprising 8-(substituted piperidino)-benzo[i,j]quinolizines their isomers, derivatives, salts, pseudopolymorphs, polymorphs and hydrates thereof. These compounds and compositions possess potent activity in treating local and systemic infections, particularly infections caused by sensitive and resistant Gram-positive organism infections, Gram-negative organism infections, mycobacterial infections and nosocomial pathogens, and particularly those belonging to the staphylococcus, streptococcus and enterococcus groups. Methods for treating the diseases and disorders arising from the foregoing infections in humans and animals are described by administering the compounds of the invention to said humans and animals.

  本发明涉及光学纯的8-(取代哌啶基)-苯[i,j]喹啉，它们的异构体、衍生物、盐、伪多晶体、多晶体、前药和水合物，以及它们的制备方法和包含8-(取代哌啶基)-苯[i,j]喹啉、它们的异构体、衍生物、盐、伪多晶体、多晶体和水合物的药物组合物。这些化合物和组合物在治疗局部和全身感染方面具有强效活性，特别是对敏感和耐药革兰氏阳性菌感染、革兰氏阴性菌感染、分枝杆菌感染和医院感染病原体，特别是属于葡萄球菌、链球菌和肠球菌群的感染具有活性。通过将本发明的化合物用于人类和动物治疗上述感染引起的疾病和疾病的方法也被描述。