7-[(3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-1,4-dihydro-8-methoxy-4-oxoquinolin-3-carboxylic acid | 181941-18-4

• 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: 7-[(3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-1,4-dihydro-8-methoxy-4-oxoquinolin-3-carboxylic acid
• 英文别名: 7-[(3R)-3-(1-Aminocyclopropyl)-1-pyrrolidinyl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid；7-[(3R)-3-(1-aminocyclopropyl)pyrrolidin-1-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxoquinoline-3-carboxylic acid
• CAS: 181941-18-4
• 化学式: C₂₁H₂₃F₂N₃O₄
• 分子量: 419.428
• InChiKey: ZPZZZGXRQMRICJ-RIEGTJTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  96.1
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  在 盐酸 、 水 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 以181 mg的产率得到7-[(3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-1,4-dihydro-8-methoxy-4-oxoquinolin-3-carboxylic acid
  参考文献：
  名称：

  Design, synthesis and biological evaluations of novel 7-[3-(1-aminocycloalkyl)pyrrolidin-1-yl]-6-desfluoro-8-methoxyquinolones with potent antibacterial activity against multi-drug resistant Gram-positive bacteria

  摘要：

  A series of novel 6-desfluoro [des-F(6)] and 6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methoxyquinolones bearing 3-(1-aminocycloalkyl)pyrrolidin-1-yl substituents at the C-7 position (1-6) was synthesized to obtain potent drugs for nosocomial infections caused by Gram-positive pathogens. The des-F(6) compounds 4-6 exhibited at least four times more potent activity against representative Gram-positive bacteria than ciprofloxacin or moxifloxacin. Among the derivatives, 7-[(3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl] derivative 4, which showed favorable profiles in preliminary toxicological and non-clinical pharmacokinetic studies, exhibited potent antibacterial activity against clinically isolated Gram-positive pathogens that had become resistant to one or more antibiotics. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.026

文献信息

• INTERMEDIATES FOR THE PRODUCTION OF OPTICALLY ACTIVE CYCLOPROPYLAMINE DERIVATIVES AND PROCESS FOR THE PRODUCTION OF THE INTERMEDIATES
  申请人：FUJITA Masao

  公开号：US20090240066A1

  公开（公告）日：2009-09-24

  The present invention provides intermediates needed for production of an optically active compound represented by formula (6), which enable the compound (6) to be readily synthesized in simple production steps without optical resolution, and also provides a process for producing the intermediates. A process for producing an optically active compound represented by formula (4): wherein R 1 represents a protecting group for the amino group, or a salt thereof, characterized in that a reagent prepared from an titanium(IV) reagent and an alkylmetal compound is reacted with an optically active compound represented by formula (3): wherein R 1 has the same meaning as defined above, if needed, in the presence of a Lewis acid.

  本发明提供了制备光学活性化合物(6)所需的中间体，使得化合物(6)可以在简单的生产步骤中无需光学分辨就能轻松合成，并提供了制备该中间体的方法。一种制备由公式(4)表示的光学活性化合物的方法：其中R1代表氨基的保护基或其盐，其特征在于将由钛(IV)试剂和烷基金属化合物制备的试剂与由公式(3)表示的光学活性化合物反应，其中R1具有与上述定义相同的含义，必要时在路易斯酸的存在下。
• Intermediates for the production of optically active cyclopropylamine derivatives and process for the production of the intermediates
  申请人：Fujita Masao

  公开号：US20070117988A1

  公开（公告）日：2007-05-24

  The present invention provides intermediates needed for production of an optically active compound represented by formula (6), which enable the compound (6) to be readily synthesized in simple production steps without optical resolution, and also provides a process for producing the intermediates. A process for producing an optically active compound represented by formula (4): wherein R 1 represents a protecting group for the amino group, or a salt thereof, characterized in that a reagent prepared from an titanium(IV) reagent and an alkylmetal compound is reacted with an optically active compound represented by formula (3): wherein R 1 has the same meaning as defined above, if needed, in the presence of a Lewis acid.

  本发明提供了制备光学活性化合物（式（6）所代表）所需的中间体，使得该化合物（6）能够在简单的生产步骤中无需光学分辨即可被合成，并且提供了制备这些中间体的方法。一种用于制备光学活性化合物（式（4）所代表）的方法：其中R1代表氨基保护基或其盐，其特征在于将由钛（IV）试剂和烷基金属化合物制备的试剂与光学活性化合物（式（3）所代表）反应，其中R1具有与上述定义相同的含义，必要时在Lewis酸的存在下进行反应。
• HETEROCYCLIC COMPOUNDS
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0807630A1

  公开（公告）日：1997-11-19

  This invention relates to a N1-(halogenocyclopropyl)-substituted pyridonecarboxylic acid derivative represented by the following formula (I): wherein X1 is a halogen atom or a hydrogen atom; X2 is a halogen atom; R1 is a hydrogen atom, a hydroxyl group, a thiol group, a halogenomethyl group, an amino group, an alkyl group or an alkoxy group which may have a substituent group; R2 is a group represented by the following formula (II): wherein R3 and R4 are independently a hydrogen atom or an alkyl group and n is an integer of 1 or 2; A is a nitrogen atom or a partial structure of the following formula (III): wherein X3 is a hydrogen atom, a halogen atom, a cyano group, an amino group, an alkyl group, a halogenomethyl group, an alkoxyl group or a halogenomethoxyl group which may have a substituent group; and R is a hydrogen atom, a phenyl group, an acetoxymethyl group, a pivaloyloxymethyl group, an ethoxycarbonyl group, a choline group, a dimethylaminoethyl group, a 5-indanyl group, a phthalidynyl group, a 5-alkyl-2-oxo-1,3-dioxol-4-ylmethyl group, a 3-acetoxy-2-oxobutyl group, an alkyl group, an alkoxymethyl group or a phenylalkyl group, and provides a heterocyclic compound useful as antibacterial drugs.

  本发明涉及由下式(I)代表的N1-(卤代环丙基)-取代的吡啶羧酸衍生物： 其中 X1 是卤素原子或氢原子；X2 是卤素原子；R1 是氢原子、羟基、硫醇基、卤代甲基、氨基、烷基或烷氧基，其中烷基或烷氧基可带有取代基；R2 是由下式（II）代表的基团： 其中 R3 和 R4 独立地为氢原子或烷基，n 为 1 或 2 的整数； A 为氮原子或下式（III）的部分结构： 其中 X3 是氢原子、卤素原子、氰基、氨基、烷基、卤代甲基、烷氧基或可带有取代基的卤代甲氧基；和 R 是氢原子、苯基、乙酰氧甲基、新戊酰氧甲基、乙氧基羰基、胆碱基、二甲基氨基乙基、5-茚基基、酞酰基、5-烷基-2-氧代-1,3-二氧戊环-4-基甲基、3-乙酰氧基-2-氧代丁基、烷基、烷氧基甲基或苯基烷基，并提供一种可用作抗菌药物的杂环化合物。
• Pyridonecarboxylic acid derivatives and their use as antibacterial agents
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1304329A2

  公开（公告）日：2003-04-23

  This invention relates to a N1-(halogenocyclopropyl)-substituted pyridonecarboxylic acid derivative represented by the following formula (I): wherein X1 is a halogen atom or a hydrogen atom; X2 is a halogen atom; R1 is a hydrogen atom, a hydroxyl group, a thiol group, a halogenomethyl group, an amino group, an alkyl group or an alkoxy group which may have a substituent group; R2 is a group represented by the following formula (II): wherein R3 and R4 are independently a hydrogen atom or an alkyl group and n is an integer of 1 or 2; A is a nitrogen atom or a partial structure of the following formula (III): wherein X3 is a hydrogen atom, a halogen atom, a cyano group, an amino group, an alkyl group, a halogenomethyl group, an alkoxyl group or a halogenomethoxyl group which may have a substituent group; and R is a hydrogen atom, a phenyl group, an acetoxymethyl group, a pivaloyloxymethyl group, an ethoxycarbonyl group, a choline group, a dimethylaminoethyl group, a 5-indanyl group, a phthalidynyl group, a 5-alkyl-2-oxo-1,3-dioxol-4-ylmethyl group, a 3-acetoxy-2-oxobutyl group, an alkyl group, an alkoxymethyl group or a phenylalkyl group, and provides a heterocyclic compound useful as antibacterial drugs.

  本发明涉及由下式(I)代表的N1-(卤代环丙基)-取代的吡啶羧酸衍生物： 其中 X1 是卤素原子或氢原子；X2 是卤素原子；R1 是氢原子、羟基、硫醇基、卤代甲基、氨基、烷基或烷氧基，其中烷基或烷氧基可带有取代基；R2 是由下式（II）代表的基团： 其中 R3 和 R4 独立地为氢原子或烷基，n 为 1 或 2 的整数； A 为氮原子或下式（III）的部分结构： 其中 X3 是氢原子、卤素原子、氰基、氨基、烷基、卤代甲基、烷氧基或可带有取代基的卤代甲氧基；和 R 是氢原子、苯基、乙酰氧甲基、新戊酰氧甲基、乙氧基羰基、胆碱基、二甲基氨基乙基、5-茚基基、酞酰基、5-烷基-2-氧代-1,3-二氧戊环-4-基甲基、3-乙酰氧基-2-氧代丁基、烷基、烷氧基甲基或苯基烷基，并提供一种可用作抗菌药物的杂环化合物。
• US5849757A
  申请人：——

  公开号：US5849757A

  公开（公告）日：1998-12-15