7-(3-Amino-pyrrolidin-1-yl)-8-chloro-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid | 112282-61-8

• 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: 7-(3-Amino-pyrrolidin-1-yl)-8-chloro-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
• 英文别名: 7-(3-Aminopyrrolidin-1-yl)-8-chloro-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 112282-61-8
• 化学式: C₁₆H₁₇ClFN₃O₃
• 分子量: 353.781
• InChiKey: FMQHVYXATGUMFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  86.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-氯-2,4,5-三氟-6-硝基苯甲酸 在 盐酸 、 正丁基锂 、 dipyridyl 、 草酰氯 、 乙酸酐 、 potassium carbonate 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 25.5h， 生成 7-(3-Amino-pyrrolidin-1-yl)-8-chloro-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00107a039

文献信息

• 8-Position substituted quinolone-carboxylic acid derivatives and process for their preparation
  申请人：KYORIN PHARMACEUTICAL CO., LTD.

  公开号：EP0235762A1

  公开（公告）日：1987-09-09

  The present invention is concerned with certain novel quinolonecarboxylic acid derivatives of the following formula, wherein R indicates chlorine, bromine, nitro, cyano,-OR2,-SR2 or -NR2R3 (here, R2 and R3 indicate hydrogen or lower alkyl each independently), R1 indicates ethyl, 4-fluorophenyl or 2,4-di-fluorophenyl, Z indicates a piperazino group of the following formula, (here, R4 indicates hydrogen, methyl or lower alkoxycarbonyl, R5 indicates hydrogen or lower alkyl) or a pyrrolidine group of the following formula, (here, n is 0 or 1, R6 indicates hydrogen or methyl, R7 indicates hydrogen atom or lower alkyl group, R8 indicates a hydrogen, lower alkyl, lower acyl or lower alkoxycarbonyl), with the proviso that when R1 is ethyl and R is chlorine, Z is not piperazino or 4-methylpiperazino; the hydrates and pharmaceutically acceptable salts thereof are useful as an antibacterial agent.

  本发明涉及下式的某些新型喹啉羧酸衍生物、 其中 R 表示氯、溴、硝基、氰基、-OR2、-SR2 或 -NR2R3 （此处 R2 和 R3 分别独立地表示氢或低级烷基），R1 表示乙基、4-氟苯基或 2，4-二氟苯基，Z 表示下式的哌嗪基团、 (此处，R4 表示氢、甲基或低级烷氧基羰基，R5 表示氢或低级烷基）或下式的吡咯烷基团、 (此处，n 为 0 或 1，R6 表示氢或甲基，R7 表示氢原子或低级烷基，R8 表示氢、低级烷基、低级酰基或低级烷氧羰基），但当 R1 为乙基、R 为氯时，Z 不是哌嗪基或 4-甲基哌嗪基；其水合物和药学上可接受的盐可用作抗菌剂。
• 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.