(S)-6,7-dihydro-5,8-dimethyl-9-fluoro-1-oxo-1H,5H-benzo(ij)quinoline-2-carboxylic acid | 107298-26-0

• 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: (S)-6,7-dihydro-5,8-dimethyl-9-fluoro-1-oxo-1H,5H-benzo(ij)quinoline-2-carboxylic acid
• 英文别名: (12S)-7-fluoro-8,12-dimethyl-4-oxo-1-azatricyclo[7.3.1.05,13]trideca-2,5,7,9(13)-tetraene-3-carboxylic acid
• CAS: 107298-26-0
• 化学式: C₁₅H₁₄FNO₃
• 分子量: 275.279
• InChiKey: DXKRGNXUIRKXNR-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-氟-2,5-二甲基-1,2,3,4-四氢喹啉 在 PPA 、 sodium ethanolate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 (S)-6,7-dihydro-5,8-dimethyl-9-fluoro-1-oxo-1H,5H-benzo(ij)quinoline-2-carboxylic acid
  参考文献：
  名称：

  Synthesis, absolute configuration, and antibacterial activity of 6,7-dihydro-5,8-dimethyl-9-fluoro-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid

  摘要：

  The tricyclic quinolone antibacterial agent 6,7-dihydro-5,8-dimethyl-9-fluoro-1-oxo-1H,5H-benzo[ij]quinolizine -2-carboxylic acid has an asymmetric center at position 5 of the molecule. The R and S isomers of the compound have been prepared from the corresponding (R)- and (S)-2,5-dimethyl-6-fluoro-1,2,3,4-tetrahydroquinolines, which were separated via their diastereomeric amides of N-tosyl-(S)-proline. The absolute configuration was established by X-ray analysis of one of the diastereomeric amides. The 5-desmethyl analogue was prepared for antibacterial comparison with the isomers and the racemic mixture. It has now been established that the S isomer is much more active than the R isomer. The 5-desmethyl analogue was found to be more active than the R isomer but not as active as the S isomer or the racemic mixture. The importance of stereochemistry at position 5 in this system has been established.

  DOI：

  10.1021/jm00388a016

文献信息

• Fused substituted aminopyrrolidine derivative
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP2540715A1

  公开（公告）日：2013-01-02

  Intermediates of formula (Ia) or (Ib) are provided: wherein R11 and R21 represents a hydrogen atom or an amino-protecting group, and R16 represents an amino-protecting group, useful for the production of quinolone synthetic antibacterial agent of formula (I) wherein substituents R6 and R7 taken together with the carbon atoms to which they are bonded form a cyclic structure which may contain an oxygen atom as a ring constituent atom, the cyclic structure forming a 5-4, 5-5, or 5-6 fused bicyclic pyrrolidinyl substituent, the substituent being bonded to a quinolone mother skeleton Q containing a pyridobenzoxazine structure:

  提供了式 (Ia) 或 (Ib) 的中间体： 其中 R11 和 R21 代表氢原子或氨基保护基团，R16 代表氨基保护基团，可用于生产式 (I) 的喹诺酮合成抗菌剂 其中取代基 R6 和 R7 与它们所结合的碳原子一起形成环状结构，该环状结构可包含一个氧原子作为环组成原子、该环状结构形成一个 5-4、5-5 或 5-6 融合的双环吡咯烷基取代基，该取代基与含有吡啶并噁嗪结构的喹诺酮母骨架 Q 键合：
• GERSTER J. F.; ROHLFING S. R.; PECORE S. E.; WINANDY R. M.; STERN R. M.; +, J. MED. CHEM., 30,(1987) N 5, 839-843
  作者：GERSTER J. F.、 ROHLFING S. R.、 PECORE S. E.、 WINANDY R. M.、 STERN R. M.、 +

  DOI：——

  日期：——
• COMPOSITION COMPRISING AN ANTIBIOTIC AND MOMETASONE
  申请人：Intervet International B.V.

  公开号：EP2293778B1

  公开（公告）日：2013-09-18
• COMPOSITION COMPRISING AN ANTIBIOTIC AND A CORTICOSTEROID
  申请人：Freehauf Keith A.

  公开号：US20100087409A1

  公开（公告）日：2010-04-08

  This invention relates to compositions (e.g., otic compositions) comprising an antibiotic (generally a quinolone or naphthyridinone), corticosteroid, and organic acid (generally a fatty acid). This invention also relates to treatment methods using such a composition, uses of such a composition to make medicaments, and therapeutic kits comprising such a composition.
• [EN] FUSED SUBSTITUTED AMINOPYRROLIDINE DERIVATIVE<br/>[FR] DÉRIVÉ D'AMINOPYRROLIDINE SUBSTITUÉ LIÉ PAR FUSION
  申请人：DAIICHI SANKYO CO LTD

  公开号：WO2008082009A2

  公开（公告）日：2008-07-10

  [EN] A quinolone synthetic antibacterial agent having excellent properties as a medicine is provided, which has strong antibacterial activity not only to Gram-negative bacteria but also to Gram-positive cocci that have low sensitivity to quinolone antibacterial agents, and which exhibits high safety and excellent pharmacokinetics. A compound represented by the formula (I) or a salt thereof, or a hydrate thereof. Specifically, a quinolone derivative of the formula (I) wherein substituents R6 and R7 taken together with the carbon atoms to which they are bonded form a cyclic structure which may contain an oxygen atom as a ring constituent atom, the cyclic structure forming a 5-4, 5-5, or 5-6 fused bicyclic pyrrolidinyl substituent, the substituent being bonded to a quinolone mother skeleton Q containing a pyridobenzoxazine structure.
  [FR] L'invention concerne un agent antibactérien synthétique de type quinolone présentant d'excellentes propriétés thérapeutiques, cet agent développant une forte activité antibactérienne, non seulement par rapport aux bactéries à Gram négatif, mais aussi par rapport aux cocci à Gram positif qui sont peut sensibles aux agents antibactériens de type quinolone, ledit agent présentant un niveau de sécurité élevé et d'excellentes propriétés de pharmacocinétique. L'invention concerne aussi un composé de formule (I) ou un sel de celui-ci ou bien un hydrate de celui-ci. L'invention porte en particulier sur un dérivé de quinolone de formule (I) dans laquelle les susbtituants R6 et R7, avec les atomes carbones auxquels ils sont liés, forment une structure cyclique qui peut contenir un atome d'oxygène en tant qu'atome constituant un noyau, la structure cyclique formant un substituant de pyrrolidinyle bicyclique lié par fusion 5-4, 5-5 ou 5-6, ce substituant étant lié à un squelette mère de quilonone Q comportant une structure pyridobenzoxazine: (I).