1-Cyclopropyl-6,8-difluoro-1,4-dihydro-5-hydroxy-4-oxo-7-[3-(methyl)-1-piperazinyl]-3-quinoline-carboxylic acid | 111230-47-8

• 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-6,8-difluoro-1,4-dihydro-5-hydroxy-4-oxo-7-[3-(methyl)-1-piperazinyl]-3-quinoline-carboxylic acid
• 英文别名: 1-Cyclopropyl-6,8-difluoro-5-hydroxy-7-(3-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid
• CAS: 111230-47-8
• 化学式: C₁₈H₁₉F₂N₃O₄
• 分子量: 379.363
• InChiKey: BNWDHRLXXHXQIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 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：
  93.1
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  ethyl 1-cyclopropyl-5,6,7,8-tetrafluoro-4(1H)-oxoquinoline-3-carboxylate 在 吡啶 、 硫酸 、 sodium hydride 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 1.84h， 生成 1-Cyclopropyl-6,8-difluoro-1,4-dihydro-5-hydroxy-4-oxo-7-[3-(methyl)-1-piperazinyl]-3-quinoline-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

• Synthesis and biological activity of 5-amino- and 5-hydroxyquinolones, and the overwhelming influence of the remote N1-substituent in determining the structure-activity relationship
  作者：John M. Domagala、Alex J. Bridges、Townley P. Culbertson、Laura Gambino、Susan E. Hagen、Gregory Karrick、Kenneth Porter、Joseph P. Sanchez、Josephine A. Sesnie

  DOI：10.1021/jm00107a039

  日期：1991.3

  A series of 5-amino- and 5-hydroxyquinolone antibacterials substituted at C7 with a select group of common piperazinyl and 3-aminopyrrolidinyl side chains was prepared. These 5-substituted derivatives were compared to the analogous 5-hydrogen compounds for antiinfective activity by using DNA gyrase inhibition, minimum inhibitory concentrations against a variety of bacteria, and in vivo efficacy in the mouse infection model. The influence on the structure-activity relationships of varied substituents at C8 (H, F, Cl) and Ni (ethyl, cyclopropyl, difluorophenyl) was also studied. The results showed that several of the structure-activity conclusions regarding side-chain bulk at C7, the effect of halogen at C8, and the effect of the C5-amino group were greatly influenced by the choice of the N1-substituent. Several outstanding broad spectrum quinolones were identified in this work. In particular, the spectrum and potency of the 7-piperazinyl quinolones could be greatly enhanced by the judicious choice of C5-, C8-, and N1-substitutents.
• 5-Amino and 5-hydroxy-6,8-difluoroquinolones as antibacterial agents
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0226961B1

  公开（公告）日：1991-06-12
• MIYAMOTO, TERUYUKI;MATSUMOTO, JUN-ICHI;CHIBA, KATSUMI;EGAWA, HIROSHI;SHIB+, J. MED. CNEM., 33,(1990) N, C. 1645-1656
  作者：MIYAMOTO, TERUYUKI、MATSUMOTO, JUN-ICHI、CHIBA, KATSUMI、EGAWA, HIROSHI、SHIB+

  DOI：——

  日期：——
• DOMAGALA, JOHN M.;BRIDGES, ALEX J.;CULBERTSON, TOWNLEY P.;GAMBINO, LAURA;+, J. MED. CHEM., 34,(1991) N, C. 1142-1154
  作者：DOMAGALA, JOHN M.、BRIDGES, ALEX J.、CULBERTSON, TOWNLEY P.、GAMBINO, LAURA、+

  DOI：——

  日期：——
• US4977154A
  申请人：——

  公开号：US4977154A

  公开（公告）日：1990-12-11