ethyl 6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate | 364069-19-2

• 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: ethyl 6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate
• 英文别名: ethyl 6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylate；Ethyl 6,7-difluoro-1-[(1R,2S)-2-fluoro-1-cyclopropyl]-1,4-dihydro-8-methoxy-4-oxo-3-quinoline Carboxylate；ethyl 6,7-difluoro-1-[(1R, 2S)-2-fluoro-1-cyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylate；ethyl 6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxoquinoline-3-carboxylate
• CAS: 364069-19-2
• 化学式: C₁₆H₁₄F₃NO₄
• 分子量: 341.287
• InChiKey: VGDZECWUDVJWEE-GXSJLCMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate 在 三乙胺 、 sodium hydroxide 作用下， 以 乙腈 为溶剂， 反应 2.5h， 生成 7-[3-(aminomethyl)-4-(ethoxyimino)pyrrolidin-1-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis, antimycobacterial and antibacterial evaluation of l-[(1R, 2S)-2-fluorocyclopropyl]fluoroquinolone derivatives containing an oxime functional moiety

  摘要：

  A series of novel 1-[(1R, 2S)-2-fluorocyclopropyl]fluoroquinolone derivatives 9a-d containing an oxime functional moiety were synthesized and evaluated for their biological activity. Our results reveal that 9a1 and 9b3 have good in vitro activity against MTB H37Rv ATCC 27294 (MIC: 0.25 mu g/mL) and two MDR-MTB clinical isolates (MICs: 0.065-0.125 mu g/mL). Most of 9a-d show potent activity against Escherichia coli and Klebsiella pneumoniae (MICs: <0.008-4 mu g/mL) except extended-spectrum beta-lactamase-producing strains. Especially, 9a1 and 9d4 possessing excellent in vitro activity against all of the fourteen Gram-positive strains including MRSA and MRSE (MICs: <0.008-2 mu g/mL) comparable to or better than the four reference drugs, show considerable in vivo efficacy against five Gram-negative and Gram-positive isolate strains (ED(50)s: 11.43-26.04 mg/kg). (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.029
• 作为产物：
  描述：

  3-甲氧基-2,4,5-三氟苯甲酸 在 四氯化碳 、 氯化亚砜 、 乙酸酐 、 potassium carbonate 、 对甲苯磺酸 、 magnesium 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.5h， 生成 ethyl 6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Synthesis, antimycobacterial and antibacterial evaluation of l-[(1R, 2S)-2-fluorocyclopropyl]fluoroquinolone derivatives containing an oxime functional moiety

  摘要：

  A series of novel 1-[(1R, 2S)-2-fluorocyclopropyl]fluoroquinolone derivatives 9a-d containing an oxime functional moiety were synthesized and evaluated for their biological activity. Our results reveal that 9a1 and 9b3 have good in vitro activity against MTB H37Rv ATCC 27294 (MIC: 0.25 mu g/mL) and two MDR-MTB clinical isolates (MICs: 0.065-0.125 mu g/mL). Most of 9a-d show potent activity against Escherichia coli and Klebsiella pneumoniae (MICs: <0.008-4 mu g/mL) except extended-spectrum beta-lactamase-producing strains. Especially, 9a1 and 9d4 possessing excellent in vitro activity against all of the fourteen Gram-positive strains including MRSA and MRSE (MICs: <0.008-2 mu g/mL) comparable to or better than the four reference drugs, show considerable in vivo efficacy against five Gram-negative and Gram-positive isolate strains (ED(50)s: 11.43-26.04 mg/kg). (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.029

文献信息

• Quinolonecarboxylic acid derivative
  申请人：——

  公开号：US20030187008A1

  公开（公告）日：2003-10-02

  (−)-7-[(7S)-7-Amino-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1-[(1R, 2S)-2-fluoro-1-cyclopropyl]-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid.1HCl.1H 2 O and antibacterial compositions containing this compound. The compound of the present invention exhibits not only excellent antibacterial activity and safety, but also remarkable stability against light and humidity, and is thus useful as an antibacterial agent.

  (-)-7-[(7S)-7-氨基-5-氮杂螺[2.4]庚烷-5-基]-6-氟-1-[(1R,2S)-2-氟-1-环丙基]-1,4-二氢-8-甲氧基-4-氧代-3-喹啉羧酸.1HCl.1H2O及含有该化合物的抗菌组合物。本发明的该化合物不仅具有优异的抗菌活性和安全性，而且对光和湿度具有显著的稳定性，因此可用作抗菌剂。
• Quinolonecarboxylic acid derivatives
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：US20040142957A1

  公开（公告）日：2004-07-22

  (−)-7-[(7S)-7-Amino-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1-[(1R, 2S)-2-fluoro-1-cyclopropyl]-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid.1HCl.1H 2 O and antibacterial compositions containing this compound. The compound of the present invention exhibits not only excellent antibacterial activity and safety, but also remarkable stability against light and humidity, and is thus useful as an antibacterial agent.

  (-)-7-[(7S)-7-氨基-5-氮杂螺[2.4]庚烷-5-基]-6-氟-1-[(1R,2S)-2-氟-1-环丙基]-1,4-二氢-8-甲氧基-4-氧基-3-喹啉羧酸.1HCl.1H2O和含有该化合物的抗菌组合物。本发明的化合物不仅具有优异的抗菌活性和安全性，而且对光和湿度具有显著的稳定性，因此可用作抗菌剂。
• 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
  作者：Rie Miyauchi、Katsuhiro Kawakami、Masao Ito、Norikazu Matsuhashi、Hitoshi Ohki、Hiroaki Inagaki、Hisashi Takahashi、Makoto Takemura

  DOI：10.1016/j.bmc.2009.08.026

  日期：2009.10

  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.
• US5545642A
  申请人：——

  公开号：US5545642A

  公开（公告）日：1996-08-13