1-Cyclopropyl-6,8-difluoro-7-(3-hydroxymethyl-piperazin-1-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylicacid ethyl ester | 479070-16-1

• 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-Cyclopropyl-6,8-difluoro-7-(3-hydroxymethyl-piperazin-1-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylicacid ethyl ester
• 英文别名: ethyl 1-cyclopropyl-6,8-difluoro-7-[3-(hydroxymethyl)piperazin-1-yl]-4-oxoquinoline-3-carboxylate
• CAS: 479070-16-1
• 化学式: C₂₀H₂₃F₂N₃O₄
• 分子量: 407.417
• InChiKey: QCMVUNUDOLFLLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  82.1
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-Cyclopropyl-6,8-difluoro-7-(3-hydroxymethyl-piperazin-1-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylicacid ethyl ester 在 lithium hydroxide 、 碳酸氢钠 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-cyclopropyl-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1H-pyrimidin-3-yl]butyl]-3-(hydroxymethyl)piperazin-1-yl]-6,8-difluoro-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Hybrid Antibacterials. DNA Polymerase−Topoisomerase Inhibitors

  摘要：

  Novel Gram-positive (Gram+) antibacterial compounds consisting of a DNA polymerase IIIC (pol IIIC) inhibitor covalently connected to a topoisomerase/gyrase inhibitor are described. Specifically, 3-substituted 6-(3-ethyl-4-methylanilino)uracils (EMAUs) in which the 3-substituent is a fluoroquinolone moiety (FQ) connected by various linkers were synthesized. The resulting "AU-FQ" hybrid compounds were significantly more potent than the parent EMAU compounds as inhibitors of pol IIIC and were up to 64-fold more potent as antibacterials in vitro against Gram+ bacteria. The hybrids inhibited the FQ targets, topoisomerase IV and gyrase, with potencies similar to norfloxacin but 10-fold lower than newer agents, for example, ciprofloxacin and sparfloxacin. Representative hybrids protected mice from lethal Staphylococcus aureus infection after intravenous dosing, and one compound showed protective effect against several antibiotic-sensitive and -resistant Gram+ infections in mice. The AU-FQ hybrids are a promising new family of antibacterials for treatment of antibiotic-resistant Gram+ infections.

  DOI：

  10.1021/jm0510023
• 作为产物：
  描述：

  哌嗪-2-甲醇 、 1-环丙基-6,7,8-三氟-1,4-二氢-4-氧代-3-喹啉羧酸乙酯 生成 1-Cyclopropyl-6,8-difluoro-7-(3-hydroxymethyl-piperazin-1-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylicacid ethyl ester
  参考文献：
  名称：

  Hybrid Antibacterials. DNA Polymerase−Topoisomerase Inhibitors

  摘要：

  Novel Gram-positive (Gram+) antibacterial compounds consisting of a DNA polymerase IIIC (pol IIIC) inhibitor covalently connected to a topoisomerase/gyrase inhibitor are described. Specifically, 3-substituted 6-(3-ethyl-4-methylanilino)uracils (EMAUs) in which the 3-substituent is a fluoroquinolone moiety (FQ) connected by various linkers were synthesized. The resulting "AU-FQ" hybrid compounds were significantly more potent than the parent EMAU compounds as inhibitors of pol IIIC and were up to 64-fold more potent as antibacterials in vitro against Gram+ bacteria. The hybrids inhibited the FQ targets, topoisomerase IV and gyrase, with potencies similar to norfloxacin but 10-fold lower than newer agents, for example, ciprofloxacin and sparfloxacin. Representative hybrids protected mice from lethal Staphylococcus aureus infection after intravenous dosing, and one compound showed protective effect against several antibiotic-sensitive and -resistant Gram+ infections in mice. The AU-FQ hybrids are a promising new family of antibacterials for treatment of antibiotic-resistant Gram+ infections.

  DOI：

  10.1021/jm0510023

文献信息

• Novel heterocyclic antibacterial compounds
  申请人：——

  公开号：US20030181719A1

  公开（公告）日：2003-09-25

  The invention provides heterocyclic organic compounds that inhibit bacterial DNA polymerase IIIC and type II bacterial topoisomerase. The invention further provides compounds that are useful as intermediates in the synthesis of such heterocyclic organic compounds. Syntheses and uses of such heterocyclic organic molecules are also described.

  该发明提供了抑制细菌DNA聚合酶IIIC和类型II细菌拓扑异构酶的杂环有机化合物。该发明还提供了在合成这种杂环有机化合物中作为中间体有用的化合物。该发明还描述了这种杂环有机分子的合成和用途。
• [EN] NOVEL HETEROCYCLIC ANTIBACTERIAL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES ANTIBACTERIENS HETEROCYCLIQUES
  申请人：MICROBIOTIX INC

  公开号：WO2002102792A1

  公开（公告）日：2002-12-27

  The invention provides heterocyclic organic compounds that inhibit bacterial DNA polymerase IIIC and type II bacterial topoisomerase. The invention further provides compounds that are useful as intermediates in the synthesis of such heterocyclic organic compounds. Syntheses and uses of such heterocyclic organic molecules are also described.

  本发明提供了一些杂环有机化合物，可抑制细菌DNA聚合酶IIIC和II型细菌拓扑异构酶。本发明还提供了一些化合物，可用作合成此类杂环有机化合物的中间体。本发明还描述了这种杂环有机分子的合成和用途。
• EP1401829A4
  申请人：——

  公开号：EP1401829A4

  公开（公告）日：2004-10-27
• NOVEL HETEROCYCLIC ANTIBACTERIAL COMPOUNDS
  申请人：Microbiotix, Inc.

  公开号：EP1401829B1

  公开（公告）日：2012-08-22
• US6777420B2
  申请人：——

  公开号：US6777420B2

  公开（公告）日：2004-08-17