5-amino-1-cyclopropyl-6,8-difluoro-7-(4-methyl-1-piperazinyl)-4(1H)-oxoquinoline-3-carboxylic acid | 110236-79-8

• 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-6,8-difluoro-7-(4-methyl-1-piperazinyl)-4(1H)-oxoquinoline-3-carboxylic acid
• 英文别名: 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-[4-(methyl)-1-piperazinyl]-4-oxo-3quinolinecarboxylic acid；5-Amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid；5-Amino-1-cyclopropyl-6,8-difluoro-7-(4-methylpiperazin-4-ium-1-yl)-4-oxoquinoline-3-carboxylate
• CAS: 110236-79-8
• 化学式: C₁₈H₂₀F₂N₄O₃
• 分子量: 378.379
• InChiKey: VSPMPXLOUWFGBD-UHFFFAOYSA-N

物化性质

• 熔点：
  247-248 °C
• 沸点：
  619.5±55.0 °C(Predicted)
• 密度：
  1.524±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  90.1
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-amino-1-cyclopropyl-6,8-difluoro-7-(4-methyl-1-piperazinyl)-4(1H)-oxoquinoline-3-carboxylic acid 在 盐酸 、 copper(l) chloride 、 sodium nitrite 作用下， 生成 5-chloro-1-cyclopropyl-6,8-difluoro-7-(4-methyl-1-piperazinyl)-4(1H)-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Pyridonecarboxylic acids as antibacterial agents. Part 14. Synthesis and structure-activity relationships of 5-substituted 6,8-difluoroquinolones, including sparfloxacin, a new quinolone antibacterial agent with improved potency

  摘要：

  A series of 5,7-disubstituted 1-cyclopropyl-6,8-difluoro-4(1H)-oxoquinoline-3-carboxylic acids (10-36) were prepared; the C-5 substituent in these compounds comprised halo, hydroxy, mercapto, and amino groups and the C-7 functional group included variously substituted piperazines. In vitro antibacterial screening results indicated that the amino group was optimal among the C-5 substituents. A combination of the C-5 amino group and the C-7 3,5-dimethylpiperazinyl appendage in this series conferred the best overall antibacterial property with lack of adverse drug interactions. Compound 36k [named sparfloxacin, originally AT-4140, 5-amino-1-cyclopropyl-6,8-difluoro-7-(cis-3,5-dimethyl-1-piperazinyl)- 4(1H)-oxoquinoline-3-carboxylic acid] was superior to ciprofloxacin in both in vitro and in vivo potency and hence was selected as a promising candidate for an improved therapeutic agent.

  DOI：

  10.1021/jm00168a018
• 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 吡啶 、 硫酸 、 溶剂黄146 作用下， 反应 0.84h， 生成 5-amino-1-cyclopropyl-6,8-difluoro-7-(4-methyl-1-piperazinyl)-4(1H)-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Pyridonecarboxylic acids as antibacterial agents. Part 14. Synthesis and structure-activity relationships of 5-substituted 6,8-difluoroquinolones, including sparfloxacin, a new quinolone antibacterial agent with improved potency

  摘要：

  A series of 5,7-disubstituted 1-cyclopropyl-6,8-difluoro-4(1H)-oxoquinoline-3-carboxylic acids (10-36) were prepared; the C-5 substituent in these compounds comprised halo, hydroxy, mercapto, and amino groups and the C-7 functional group included variously substituted piperazines. In vitro antibacterial screening results indicated that the amino group was optimal among the C-5 substituents. A combination of the C-5 amino group and the C-7 3,5-dimethylpiperazinyl appendage in this series conferred the best overall antibacterial property with lack of adverse drug interactions. Compound 36k [named sparfloxacin, originally AT-4140, 5-amino-1-cyclopropyl-6,8-difluoro-7-(cis-3,5-dimethyl-1-piperazinyl)- 4(1H)-oxoquinoline-3-carboxylic acid] was superior to ciprofloxacin in both in vitro and in vivo potency and hence was selected as a promising candidate for an improved therapeutic agent.

  DOI：

  10.1021/jm00168a018

文献信息

• 5-amino and 5-hydroxy-6-fluoroquinolones as antibacterial agents
  申请人：Warner-Lambert Company

  公开号：US04977154A1

  公开（公告）日：1990-12-11

  Novel 7-piperazine derivatives of 5-amino- and 5-hydroxy-1-cyclopropyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids as antibacterial agents are described as well as methods for their manufacture, formulation, and use in treating bacterial infections.

  本发明涉及7-哌嗪衍生物的新型抗菌剂，其基础结构为5-氨基-和5-羟基-1-环丙基-1,4-二氢-4-氧喹啉-3-羧酸，并描述了它们的制备方法、配方和用于治疗细菌感染的用途。
• 5-amino-6,8-difluoroquinolones as antibacterial agents
  申请人：Warner-Lambert Company

  公开号：US04668680A1

  公开（公告）日：1987-05-26

  Novel 7-piperazino and 7-N-methylpiperazino derivatives of 5-amino-1-cyclopropyl-6,8-dihydro-1,4-dihydro-4-oxoquinoline-3-carboxylic acids as antibacterial agents are described as well as methods for their manaufacture, formulation, and use in treating bacterial infections.

  描述了一种7-哌嗪基和7-N-甲基哌嗪基衍生物，它们是5-氨基-1-环丙基-6,8-二氢-1,4-二氢-4-氧基喹诺酮-3-羧酸的抗菌剂，并介绍了它们的制造、配方和用于治疗细菌感染的方法。
• 5-substituted-6,8-difluoroquinolines useful as antibacterial agents
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US04795751A1

  公开（公告）日：1989-01-03

  The present invention relates to a quinoline derivative of the formula ##STR1## wherein Z is an amino group or a halogen atom, R.sub.1 is a hydrogen atom or a methyl or ethyl group, R.sub.2 is a hydrogen atom or a methyl or fluoromethyl group, R.sub.3 and R.sub.4 are the same or different and each represents a hydrogen atom or a methyl group, and n is 1 or 2; and esters thereof and salts thereof and processes for preparation thereof. These compounds show excellent antibacterial activity and are useful antibacterial agents.

  本发明涉及一种喹啉衍生物，其化学式为##STR1## 其中Z是氨基或卤素原子，R.sub.1是氢原子或甲基或乙基基团，R.sub.2是氢原子或甲基或氟甲基基团，R.sub.3和R.sub.4相同或不同，分别表示氢原子或甲基基团，n为1或2;以及它们的酯和盐及其制备方法。这些化合物表现出优异的抗菌活性，是有用的抗菌剂。
• Quinoline derivatives and processes for preparation thereof
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：EP0221463A2

  公开（公告）日：1987-05-13

  The present invention relates to a quinoline derivative of the formula wherein Z is an amino group or a halogen atom, R, is a hydrogen atom or a methyl or ethyl group, R2 is a hydrogen atom or a methyl or fluoromethyl group, R3 and R4 are the same or different and each represents a hydrogen atom or a methyl group, and n is 1 or 2; and esters thereof and salts thereof and processes for preparation thereof. These compounds show excellent antibacterial activity and are useful antibacterial agents.

  本发明涉及一种式如下的喹啉衍生物 其中 Z 是氨基或卤原子，R, 是氢原子或甲基或乙基，R2 是氢原子或甲基或氟甲基，R3 和 R4 相同或不同且各自代表氢原子或甲基，n 是 1 或 2； 及其酯类、盐类和制备工艺。这些化合物显示出卓越的抗菌活性，是有用的抗菌剂。
• 5-Amino and 5-hydroxy-6,8-difluoroquinolones as antibacterial agents
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0226961A1

  公开（公告）日：1987-07-01

  Novel 7-piperazine derivatives of 5-amino- and 5-hydroxy-1-cyclopropyl-1,4-dihydro-4-oxoquinoline-3-­carboxylic acids as antibacterial agents are described as well as methods for their manufacture, formulation, and use in treating bacterial infections.

  介绍了作为抗菌剂的 5-氨基-和 5-羟基-1-环丙基-1,4-二氢-4-氧代喹啉-3-羧酸的新型 7-哌嗪衍生物及其生产、配制和用于治疗细菌感染的方法。