1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-quinoline-3-carboxylic acid | 107564-07-8

• 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: 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-quinoline-3-carboxylic acid
• 英文别名: 1-cyclopropyl-5,6,8-trifluoro-7-(4-methyl-1-piperazynyl)-4(1H)-oxoquinoline-3-carboxylic acid；7-(4-methyl-1-piperazinyl)-1-cyclopropyl-5,6,8-trifluoro-4(1H)-oxoquinoline-3-carboxylic acid；1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid；1-Cyclopropyl-5,6,8-trifluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid；1-cyclopropyl-5,6,8-trifluoro-7-(4-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid
• CAS: 107564-07-8
• 化学式: C₁₈H₁₈F₃N₃O₃
• 分子量: 381.354
• InChiKey: QZGZNEIHSDIMDE-UHFFFAOYSA-N

物化性质

• 熔点：
  256 °C
• 沸点：
  568.4±50.0 °C(Predicted)
• 密度：
  1.524±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 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：
  64.1
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-quinoline-3-carboxylic acid 在 palladium on activated charcoal 盐酸 、 氢气 、 copper(l) chloride 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 1.25h， 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：

  ethyl 1-cyclopropyl-5,6,7,8-tetrafluoro-4(1H)-oxoquinoline-3-carboxylate 在 硫酸 作用下， 以 various solvent(s) 为溶剂， 生成 1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-quinoline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis of novel 5-fluoro analogs of norfloxacin and ciprofloxacin

  摘要：

  A series of polyfluoro-3-quinolonecarboxylic acids have been synthesized and their in vitro antibacterial activity evaluated. The desired 7-(substituted amino) derivatives were prepared from the 5,6,7,8-tetrafluoroquinolone acids. Conversely, amine displacement occurred primarily at the 5-position when the ester was used. Structure-activity studies indicated that the antibacterial activity was greatest when the N-1 substituent was cyclopropyl and the 7-substituent was 4-methyl-1-piperazinyl. All 5-(substituted amino) derivatives showed poor in vitro activity.

  DOI：

  10.1021/jm00126a028

文献信息

• 7-(substituted)piperaziny
  申请人：American Cyanamid Company

  公开号：US04940710A1

  公开（公告）日：1990-07-10

  7-(substituted)piperazinyl-1-ethyl-6-fluoro-4-oxo-3-quinolinecarboxylic acids, the pharmacologically acceptable salts thereof, compositions containing them, processes and intermediates for producing them, and methods of using them to treat bacterial infections in warm-blooded animals.

  7-(取代)哌嗪基-1-乙基-6-氟-4-氧代-3-喹啉羧酸，其药理上可接受的盐，含有它们的组合物，生产它们的过程和中间体，以及使用它们治疗温血动物细菌感染的方法。
• Pyridonecarboxylic acids as antibacterial agents. Part XIII. Regioselective displacement reactions of 1-cyclopropyl-5,6,7,8-tetrafluoro-4(1H)-oxoquinoline-3-carboxylic acid with amine nucleophiles.
  作者：Koh-ichiro SHIBAMORI、Hiroshi EGAWA、Teruyuki MIYAMOTO、Yoshiro NISHIMURA、Akira ITOKAWA、Junji NAKANO、Jun-ichi MATSUMOTO

  DOI：10.1248/cpb.38.2390

  日期：——

  The displacement reactions of ethyl 1-cyclopropyl-5, 6, 7, 8-tetrafluoro-4(1H)-oxoquinoline-3-carboxylate (7) and its carboxylic acid 8 with amine nucleophiles were examined. The nucleophilic displacement occurred regioselectively at the C-5 or C-7 position depending on the substrate (7 or 8) and solvent selected; this finding permitted the introduction of an optional nucleophile preferentially into the required position at either C-5 or C-7, or into both positions with a desired combination of nucleophiles. Taking advantage of this regioselectivity, we prepared various 5-substituted 6, 7, 8-trifluoro- and 7-substituted 5, 6, 8-trifluoro-1-cyclopropyl-4(1H)-oxoquinoline-3-carboxylic acids. Furthermore, the use of the boron-chelated derivative of the carboxylic acid 8 was favorable for the regioselective synthesis of 7-substituted 5, 6, 8-trifluoroquinolones.

  研究了1-环丙基-5,6,7,8-四氟-4(1H)-氧代喹啉-3-甲酸乙酯(7)及其羧酸8与胺亲核试剂的置换反应。根据所选择的底物（7 或 8）和溶剂，亲核置换区域选择性地发生在 C-5 或 C-7 位置；这一发现允许将任选的亲核试剂优先引入到所需的C-5或C-7位置，或者引入具有所需亲核试剂组合的两个位置。利用这种区域选择性，我们制备了各种5-取代的6,7,8-三氟-和7-取代的5,6,8-三氟-1-环丙基-4(1H)-氧代喹啉-3-羧酸。此外，使用羧酸8的硼螯合衍生物有利于7-取代的5,6,8-三氟喹诺酮的区域选择性合成。
• 5-Substituierte Chinolon- und Naphthyridoncarbonsäure-Derivate
  申请人：BAYER AG

  公开号：EP0284935A1

  公开（公告）日：1988-10-05

  Die Erfindung betrifft 5-substituierte Chinolon-und Naphthyridoncarbonsäure-Derivate der Formel (I) in welcher X, Y, R', R2 und R3 die in der Beschreibung angegebene Bedeutung haben. Verfahren zu ihrer Herstellung sowie diese enthaltende antibakterielle Mittel und Futterzusatzstoffe.

  本发明涉及式(I)的5-取代喹诺酮和萘啶酮羧酸衍生物，其中X，Y，R'，R2和R3具有描述中所述的含义。制备它们的方法以及包含它们的抗菌剂和饲料添加剂。
• 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。
• Novel therapeutic agents that modulate enzymatic processes
  申请人：——

  公开号：US20040023290A1

  公开（公告）日：2004-02-05

  Novel multi-binding compounds are disclosed that modulate enzymatic processes. The compounds of the invention comprise from 2-10 ligands covalently connected, each of said ligands being capable of binding to an enzyme, enzyme substrate or enzyme cofactor thereby modulating the biological processes/functions thereof.

  本发明揭示了一种多重结合化合物，可调节酶过程。该发明的化合物包括2-10个共价连接的配体，每个配体都能够结合到酶、酶底物或酶辅因子上，从而调节其生物过程/功能。