1-(6-amino-3,5-difluoropyridin-2-yl)-6,7-difluoro-8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 189280-68-0

• 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: 1-(6-amino-3,5-difluoropyridin-2-yl)-6,7-difluoro-8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 1-(6-amino-3,5-difluoropyridin-2-yl)-6,7-difluoro-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid；1-(6-Amino-3,5-difluoropyridin-2-yl)-6,7-difluoro-8-methyl-4-oxo-1,4-dihydroquinolin-3-carboxylic acid；1-(6-amino-3,5-difluoropyridin-2-yl)-6,7-difluoro-8-methyl-4-oxoquinoline-3-carboxylic acid
• CAS: 189280-68-0
• 化学式: C₁₆H₉F₄N₃O₃
• 分子量: 367.259
• InChiKey: IISVLEZRABBUIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  96.5
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-(6-amino-3,5-difluoropyridin-2-yl)-6,7-difluoro-8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 、 3-羟基氮杂环丁烷盐酸盐 在 lithium hydroxide 、 氯化镁 、 柠檬酸 作用下， 以 吡啶 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 生成 1-(6-amino-3,5-difluoropyridin-2-yl)-6-fluoro-7-(3-hydroxyazetidin-1-yl)-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Quinolinecarboxylic acid derivative or its salt

  摘要：

  本发明涉及一种1-(6-氨基-3,5-二氟吡啶-2-基)-6-氟-7-(3-羟基氮杂环戊烷-1-基)-8-甲基-1,4-二氢-4-氧喹诺酮-3-羧酸或其盐；以及含有该化合物作为活性成分的药物。由于该化合物或其盐对光高度稳定，同时保持喹诺酮类抗菌剂固有的优良特性，因此，包含该发明化合物或其盐作为活性成分的抗菌剂可以长时间存储，而不会出现药效降低，因此可以作为稳定的制剂，如注射剂、眼药水和外科药品供应。

  公开号：

  US06586420B1
• 作为产物：
  描述：

  2,3,5,6-四氟吡啶 在 盐酸 、 palladium 10% on activated carbon 、 氢气 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 乙醇 、 水 、 乙腈 为溶剂， 反应 121.16h， 生成 1-(6-amino-3,5-difluoropyridin-2-yl)-6,7-difluoro-8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Discovery of WQ-3810: Design, synthesis, and evaluation of 7-(3-alkylaminoazetidin-1-yl)fluoro-quinolones as orally active antibacterial agents

  摘要：

  Novel 7-(3-allcylaminoazetidin-1-yl)fluoroquinolones were designed, synthesized, and evaluated for their antibacterial activities and oral absorption rates. Against Gram-negative bacteria, 10a-e, which have various alkyl groups containing different numbers of carbon atoms (C0-C3) at the C-7 alkylaminoazetidine position, showed potent and similar antibacterial activities, whereas the activity of 10f (C4, t-Bu) was significantly lower than those of 10a-e. Conversely, the oral absorption rates of 10a-e in rats increased depending on the number of carbon atoms in the alkyl groups; 10d (C3, n-Pr) and 10e (C3, i-Pr) had high oral absorption rates (>90% at 10 mg/kg). These results demonstrated that the introduction of alkyl groups onto C-7 aminoazetidine is useful for the improvement of the oral absorption rates of these drugs while maintaining their antibacterial activities. As a conclusion, from this series of fluoroquinolones, WQ-3810 (10e), having 3-isopropylaminoazetidine as the C-7 substituent, was identified as an orally active antibacterial agent with a potent in vitro activity. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.015

文献信息

• Pyridonecarboxylic acid derivatives or their salts and antibacterial
  申请人：Wakunaga Pharmaceuticals Co., Ltd.

  公开号：US05998436A1

  公开（公告）日：1999-12-07

  A pyridonecarboxylic acid derivative represented by the following general formula (1): ##STR1## [wherein R.sup.1 represents hydrogen atom or a carboxyl protective group; R.sup.2 represents hydroxyl group, a lower alkoxy group, or a substituted or unsubstituted amino group; R.sup.3 represents hydrogen atom or a halogen atom; R.sup.4 represents hydrogen atom or a halogen atom; R.sup.5 represents a halogen atom or an optionally substituted saturated cyclic amino group; R.sup.6 represents hydrogen atom, a halogen atom, nitro group, or an optionally protected amino group; X, Y and Z may be the same or different and respectively represent nitrogen atom, --CH.dbd. or --CR.sup.7 .dbd. (wherein R.sup.7 represents a lower alkyl group, a halogen atom, or cyano group) (with the proviso that at least one of X, Y and Z represent the nitrogen atom), and W represents nitrogen atom or --CR.sup.8 .dbd. (wherein R.sup.8 represents hydrogen atom, a halogen atom, or a lower alkyl group)] or its salt, as well as an antibacterial agent containing such compound are provided.

  一种吡啶酮羧酸衍生物，由以下通式（1）表示： ##STR1## [其中R1表示氢原子或羧基保护基团；R2表示羟基、低级烷氧基或取代或未取代的氨基；R3表示氢原子或卤素原子；R4表示氢原子或卤素原子；R5表示卤素原子或可选择性取代的饱和环状氨基；R6表示氢原子、卤素原子、硝基或可选择性保护的氨基；X、Y和Z可以相同或不同，分别表示氮原子、--CH＝或--CR7＝（其中R7表示低级烷基、卤素原子或氰基）（条件是X、Y和Z中至少有一个表示氮原子），W表示氮原子或--CR8＝（其中R8表示氢原子、卤素原子或低级烷基）]或其盐，以及含有此类化合物的抗菌剂。
• Pyridonecarboxylic acid derivatives or their salts, and antibacterial
  申请人：Wakunaga Pharmaceutical Co., Ltd.

  公开号：US06133284A1

  公开（公告）日：2000-10-17

  A pyridonecarboxylic acid derivative represented by the following general formula (1): ##STR1## [wherein R.sup.1 represents hydrogen atom or a carboxyl protective group; R.sup.2 represents hydroxyl group, a lower alkoxy group, or a substituted or unsubstituted amino group; R.sup.3 represents hydrogen atom or a halogen atom; R.sup.4 represents hydrogen atom or a halogen atom; R.sup.5 represents a halogen atom or an optionally substituted saturated cyclic amino group; R.sup.6 represents hydrogen atom, a halogen atom, nitro group, or an optionally protected amino group; X, Y and Z may be the same or different and respectively represent nitrogen atom, --CH.dbd. or --CR.sup.7 .dbd. (wherein R.sup.7 represents a lower alkyl group, a halogen atom, or cyano group) (with the proviso that at least one of X, Y and Z represent the nitrogen atom), and W represents nitrogen atom or --CR.sup.8 .dbd. (wherein R.sup.8 represents hydrogen atom, a halogen atom, or a lower alkyl group)] or its salt, as well as an antibacterial agent containing such compound are provided.

  提供一种由以下通式（1）表示的吡啶酮羧酸衍生物：##STR1## [其中，R.sup.1表示氢原子或羧基保护基；R.sup.2表示羟基、低级烷氧基或取代或未取代的氨基；R.sup.3表示氢原子或卤素原子；R.sup.4表示氢原子或卤素原子；R.sup.5表示卤素原子或可选取代的饱和环氨基基团；R.sup.6表示氢原子、卤素原子、硝基基团或可选保护的氨基基团；X、Y和Z可以相同也可以不同，分别表示氮原子、--CH.dbd.或--CR.sup.7.dbd.（其中，R.sup.7表示低级烷基、卤素原子或氰基）（但至少其中一个为氮原子），W表示氮原子或--CR.sup.8.dbd.（其中，R.sup.8表示氢原子、卤素原子或低级烷基）]或其盐，以及含有此类化合物的抗菌剂。
• Intermediates for use in preparing novel pyridonecarboxylic acid derivatives or their salts
  申请人：WAKUNAGA PHARMACEUTICAL CO., LTD.

  公开号：EP0952151A2

  公开（公告）日：1999-10-27

  An intermediate useful for preparing novel pyridonecarboxylic acid derivatives or their salts, the intermediate represented by the following general formula (C) : wherein X represents a nitrogen atom, Y represents -CH= or -CR7= (wherein R7 represents a lower alkyl group or a halogen atom), Z represents -CH=, R2a represents a substituted or unsubstituted amino group substituted with a protect group and R3 represents a hydrogen atom or a halogen atom.

  一种用于制备新型吡啶羧酸衍生物或其盐类的中间体，该中间体由以下通式（C）代表： 其中 X 代表氮原子，Y 代表 -CH= 或 -CR7=（其中 R7 代表低级烷基或卤素原子），Z 代表 -CH=，R2a 代表被保护基团取代或未被取代的氨基，R3 代表氢原子或卤素原子。
• Pyridonecarboxylic acid derivatives as antibacterial agents
  申请人：WAKUNAGA PHARMACEUTICAL CO., LTD.

  公开号：EP0992501A2

  公开（公告）日：2000-04-12

  A pyridonecarboxylic acid compound of the formula or salt thereof is useful as an antibacterial agent.

  式中的吡啶羧酸化合物或其盐可用作抗菌剂。 或其盐可用作抗菌剂。
• QUINOLINECARBOXYLIC ACID DERIVATIVE OR ITS SALT
  申请人：WAKUNAGA PHARMACEUTICAL CO., LTD.

  公开号：EP1219618A1

  公开（公告）日：2002-07-03

  The present invention relates to a 1-(6-amino-3,5-difluoropyridin-2-yl)-6-fluoro-7-(3-hydroxyazetidin-1-yl)-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid or salt thereof; and drugs containing the same as the active ingredient. Since this compound or salt thereof is highly stable to light while sustaining the excellent properties inherent to quinolone antibacterial agents, an antibacterial agent comprising, as an active ingredient, the invention compound or salt thereof can be stored over a long period of time without suffering from any decrease in the drug effect and can therefore be supplied as stable preparations such as injections, eye drops and surgical medicines.

  本发明涉及一种 1-(6-氨基-3,5-二氟吡啶-2-基)-6-氟-7-(3-羟基氮杂环丁烷-1-基)-8-甲基-1,4-二氢-4-氧代喹啉-3-羧酸或其盐，以及以其为活性成分的药物。由于这种化合物或其盐对光高度稳定，同时又保持了喹诺酮类抗菌剂固有的优良特性，因此含有本发明化合物或其盐作为有效成分的抗菌剂可以长期储存而不会降低药效，因此可以作为注射剂、滴眼剂和手术药物等稳定制剂供应。