5-amino-1-cyclopropyl-7-chloro-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid | 140412-79-9

• 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: 5-amino-1-cyclopropyl-7-chloro-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid
• 英文别名: 5-Amino-7-chloro-1-cyclopropyl-6,8-difluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 140412-79-9
• 化学式: C₁₃H₉ClF₂N₂O₃
• 分子量: 314.676
• InChiKey: SRGLHWWZZXXJBL-UHFFFAOYSA-N

物化性质

• 沸点：
  546.4±50.0 °C(Predicted)
• 密度：
  1.778±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-amino-1-cyclopropyl-7-chloro-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid 在 盐酸 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 7.0h， 生成 5-Amino-7-[(R)-3-((S)-2-amino-propionylamino)-pyrrolidin-1-yl]-1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid; hydrochloride
  参考文献：
  名称：

  Quinolone antibacterial agents. Synthesis and structure-activity relationships of a series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)quinolones. Highly soluble quinolone prodrugs with in vivo pseudomonas activity

  摘要：

  A series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,8-naphthyridine-3-carboxylic acids, 1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids, 1-cyclopropyl-6-fluoro-3-quinolinecarboxylic acids, and 5-amino-1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids have been prepared and evaluated for comparative antibacterial activity. Compounds were prepared by acylation of the 3-amino group of the pyrrolidine with common amino acids using standard peptide chemistry. This series has been compared with the parent compounds for antibacterial activity in vitro and in vivo as well as for comparatively solubility. The amino acid analogues were less active in vitro, but had equal or increased efficacy in vivo. Indeed, it was proven that these compounds, which were stable to acid and base under the reaction conditions for their preparation, were rapidly cleaved in serum to give the parent quinolones. The amino acid derivatives showed a 3-70 times improved solubility when compared to the parent compounds. The most active compound of the series was [S-(R*,R*)]-7-[3-[2-amino-1-oxopropyl)-amino]-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (PD 131112).

  DOI：

  10.1021/jm00088a011
• 作为产物：
  描述：

  1-环丙基-5-酰胺-6,7,8-三氟-1,4-二氢-4-氧代-3-喹啉羧酸乙酯 在 硫酸 、 溶剂黄146 作用下， 以 水 为溶剂， 以96.8%的产率得到5-amino-1-cyclopropyl-7-chloro-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid
  参考文献：
  名称：

  Process for preparing a quinolone-carboxylic acid

  摘要：

  本发明提供了一种制备具有以下式（I）的喹诺酮羧酸衍生物的方法： 其中R1为H、卤素或氨基；R2为卤素；R3为H、卤素、C1-4烷氧基或CN；R4选自C3-6环烷基、C1-4烷基、C1-4烷氧基C1-4烷基和C1-4烷基氨基C1-4烷基的群组。该发明还提供了新的具有以下式（II）的苯乙酮，这些苯乙酮是制备上述式（I）化合物的中间体。

  公开号：

  US20030166936A1

文献信息

• A NEW PROCESS FOR PREPARING A QUINOLONE-CARBOXYLIC ACID
  申请人：Lynchem Co., Ltd.

  公开号：EP1319656A1

  公开（公告）日：2003-06-18

  The present invention provides a process for preparing quinolinecarboxylic acid derivatives having the formula (I): wherein R1 is H, halogen, or amino; R2 is halogen; R3 is H, halogen, C1-4 alkoxyl, or CN; R4 is selected from the group consisting of C3-6cycloalkyl, C1-4alkyl, C1-4 alkoxyC1-4alkyl, and C1-4alkylaminoC1-4alkyl. The invention also provides new acetophenones having the formula (II) that are intermediates for preparing the compound of the formula (I).

  本发明提供了一种制备具有式（I）的喹啉羧酸衍生物的工艺： 其中R1为H、卤素或氨基；R2为卤素；R3为H、卤素、C1-4烷氧基或CN；R4选自由C3-6环烷基、C1-4烷基、C1-4烷氧基C1-4烷基和C1-4烷基氨基C1-4烷基组成的组。本发明还提供了具有式（II）的新苯乙酮，它们是制备式（I）化合物的中间体。
• Novel Fluoroquinolone Antibacterial Agents Containing Oxime-Substituted (Aminomethyl)pyrrolidines:  Synthesis and Antibacterial Activity of 7-(4-(Aminomethyl)-3-(methoxyimino)pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro- 4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic Acid (LB20304)^,1
  作者：Chang Yong Hong、Young Kwan Kim、Jay Hyok Chang、Se Ho Kim、Hoon Choi、Do Hyun Nam、Yong Zu Kim、Jin Hwan Kwak

  DOI：10.1021/jm970202e

  日期：1997.10.1

  New pyrrolidine derivatives, which bear an alkyloxime substituent in the 4-position and an aminomethyl substituent in the 3-position of the pyrrolidine ring, have been synthesized and coupled with various quinolinecarboxylic acids to produce a series of new fluoroquinolone antibacterials. These fluoroquinolones were found to possess potent antimicrobial activity against both Gram-negative and Gram-positive organisms, including methicillin resistant Staphylococcus aureus (MRSA). Variations at the C-8 position of the quinolone nucleus included fluorine, chlorine, nitrogen, methoxy, and hydrogen atom substitution. The activity imparted to the substituted quinolone nucleus by the C-8 substituent was in the order F (C-5-NH2) > F (C-5-H) > naphthyridine > Cl = OMe = H against Gram-positive organisms. In the case of Gram-negative strains, activity was in the order F (C-5-NH2) > naphthyridine = F (C-5-H) > H > Cl > OMe. The advantages provided by the newly introduced oxime group of the quinolones were clearly demonstrated by their comparison to a desoximino compound 30. In addition, the oxime moiety greatly improved the pharmacokinetic parameters of the novel quinolones. Among these compounds, compound 20 (LB20304) showed the best in vivo efficacy and pharmacokinetic profile in animals, as well as good physical properties. The MICs (mu g/mL) of LB20304, compound 30, and ciprofloxacin against several test organisms are as follows: S. aureus 6538p (0.008, 0.031, and 0.13), methicillin resistant S. aureus 241 (4, 16, and 128), Streptococcus epidermidis 887E (0.008, 0.016, and 0.13), methicillin resistant S. epidermidis 178 (4, 32, and 128), Enterococcus faecalis 29212 (0.063, 0.13, and 1), Pseudomonas aeruginosa 1912E (0.25, 0.5, and 0.13), Escherichia coli 3190Y (0.008, 0.016, and 0.008), Enterobacter cloacae P99 (0.008, 0.031, and 0.008), Acinobacter calcoaceticus 15473 (0.063, 0.13, and 0.25). On the basis of these promising results, LB20304 was selected as a candidate for further evaluation.
• US6699992B2
  申请人：——

  公开号：US6699992B2

  公开（公告）日：2004-03-02