1-ethyl-6,7-difluoro-8-chloro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid | 80076-53-5

• 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-ethyl-6,7-difluoro-8-chloro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid
• 英文别名: 8-chloro-1-ethyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid；8-chloro-1-ethyl-6,7-difluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 80076-53-5
• 化学式: C₁₂H₈ClF₂NO₃
• 分子量: 287.65
• InChiKey: GHHJVASDDBUKCH-UHFFFAOYSA-N

物化性质

• 熔点：
  216-218 °C
• 沸点：
  437.6±45.0 °C(Predicted)
• 密度：
  1.552±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-甲基哌嗪 、 1-ethyl-6,7-difluoro-8-chloro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 以 N,N-二甲基甲酰胺 为溶剂， 以76%的产率得到洛美沙星杂质
  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
• 作为产物：
  描述：

  Ethyl 8-chloro-1-ethyl-6,7-difluoro-4-oxoquinoline-3-carboxylate 在 盐酸 作用下， 以 水 为溶剂， 反应 2.0h， 生成 1-ethyl-6,7-difluoro-8-chloro-1,4-dihydro-4-oxoquinoline-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

• 7-Azetidinylquinolones as Antibacterial Agents. 2. Synthesis and Biological Activity of 7-(2,3-Disubstituted-1-azetidinyl)-4-oxoquinoline- and -1,8-naphthyridine-3-carboxylic Acids. Properties and Structure-Activity Relationships of Quinolones with an Azetidine Moiety
  作者：Jordi Frigola、Antoni Torrens、Jose A. Castrillo、Josep Mas、David Vano、Juana M. Berrocal、Carme Calvet、Leonardo Salgado、Jordi Redondo

  DOI：10.1021/jm00050a016

  日期：1994.11

  3-disubstituted-1-azetidinyl)-1,4-dihydro-6-fluoro-4- oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids, with varied substituents at the 1-, 5-, and 8-positions, was prepared to study the effects on potency and physicochemical properties of the substituent at position 2 of the azetidine moiety. The activity of the title compounds was determined in vitro against Gram-positive and Gram-negative bacteria

  一系列7-（2,3-二取代-1-氮杂环丁烷基）-1,4-二氢-6-氟-4-氧代喹啉-和-1,8-萘啶-3-羧酸，在1处具有不同的取代基制备5-，5-和8-位，以研究对氮杂环丁烷部分2位上的取代基的效能和理化性质的影响。在体外确定针对革兰氏阳性和革兰氏阴性细菌的标题化合物的活性，并使用小鼠感染模型确定所选衍生物的体内功效。发现6b，6c和6d的X射线晶体结构与相应的AM1计算的几何结构合理吻合。建立了所有合成的7-氮杂环丁烷基喹诺酮类和萘啶类的抗菌能力与计算出的电子性质和实验容量因子之间的相关性。将所选衍生物的抗菌功效，药代动力学和理化性质与相关的7-（3-氨基-1-氮杂环丁烷基）和7-（3-氨基-3-甲基-1-氮杂环丁烷基）类似物进行了比较（第1部分，请参见： J. Med。Chem。1993，36，801-810）。N-1处的环丙基或取代的苯基与C-7处的反-3-氨基-2-甲基-1-氮杂
• Pyridonecarboxylic acid derivatives and antibacterial pharmaceutical
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：US04753953A1

  公开（公告）日：1988-06-28

  Pyridonecarboxylic acid derivatives of the following formula, ##STR1## wherein R is hydrogen atom or lower alkyl group, R.sup.1 is lower alkyl group, cycloalkyl group or haloalkyl group, Y is hydrogen atom or halogen atom, or Y and R.sup.1 are ##STR2## which work together, R.sup.2 is hydrogen atom, lower alkyl group, alkoxycarbonyl group or acyl group and n is 0 or 1; the hydrates and pharmaceutically acceptable salts thereof are useful as antibacterial agents.

  以下式的吡啶酮羧酸衍生物，其中R是氢原子或较低的烷基基团，R.sup.1是较低的烷基基团、环烷基基团或卤代烷基基团，Y是氢原子或卤原子，或Y和R.sup.1是一起工作的，R.sup.2是氢原子、较低的烷基基团、烷氧羰基基团或酰基，n为0或1；其水合物和药学上可接受的盐被用作抗菌剂。
• Pyridonecarboxylic acid derivatives and process for their preparation
  申请人：KYORIN PHARMACEUTICAL CO., LTD.

  公开号：EP0208210A1

  公开（公告）日：1987-01-14

  Pyridonecarboxylic acid derivatives of the following formula. wherein R is hydrogen atom or lower alkyl group, R1 is lower alkyl group, cycloalkyl group or haloalkyl group, Y is hydrogen atom or halogen atom, or Y and R1 are which work together, R2 is hydrogen atom, lower alkyl group, alkoxycarbonyl group or acyl group and n is 0 or 1; the hydrates and pharmaceutically acceptable salts thereof are useful as antibacterial agents.

  下式的吡啶羧酸衍生物。 其中 R 是氢原子或低级烷基，R1 是低级烷基、环烷基或卤代烷基，Y 是氢原子或卤素原子，或 Y 和 R1 是 共同作用，R2 是氢原子、低级烷基、烷氧羰基或酰基，n 是 0 或 1；其水合物和药学上可接受的盐可用作抗菌剂。
• 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。
• Antibacterial quinolone carboxylic acid derivatives
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY

  公开号：EP0549857A1

  公开（公告）日：1993-07-07

  The present invention relates to certain novel quinolone compounds of the present invention represented by the following formula(I) and novel processes for preparing same. wherein: X isa nitrogen atom or a C-Y group wherein Y is a hydrogen, fluorine, chlorine or bromine atom or a methoxy or methyl group; R₁ isa C₁₋₆ alkyl group optionally substituted with a halogen atom or a hydroxy radical, an alkenyl group, a C₃₋₆ cycloalkyl group, a phenyl group substituted with a halogen atom or a divalent group of -OCH₂*CH(CH₃)-, -SCH₂*CH₂-or -SCH₂*CH(CH₃)- which forms an oxazine or thiazine ring together with the nitrogen atom to which R₁ is attached and with X wherein X is C-Y; R₂ isa hydrogen atom, a carboxy protecting group or a pharmaceutically acceptable metal or organic cation; R₃ and R₄,which may be the same or different, are a hydrogen atom, a lower alkyl group, an acyl group or a nitrogen protecting group metabolizable in vivo; Z isa hydrogen or halogen atom, an amino, hydroxy or methyl group; and n is1 to 3.

  本发明涉及下式(I)所代表的本发明的某些新型喹诺酮化合物及其新型制备工艺。 其中 X 是氮原子或 C-Y 基团，其中 Y 是氢、氟、氯或溴原子或甲氧基或甲基； R₁ 是任选被卤素原子或羟基取代的 C₁₋₆ 烷基、烯基、C₃₋₆ 环烷基、被卤素原子取代的苯基或 -OCH₂*CH(CH₃)- 的二价基团、-SCH₂*CH₂-或 -SCH₂*CH(CH₃)-，它们与 R₁ 所连接的氮原子和 X 一起形成噁嗪环或噻嗪环，其中 X 为 C-Y； R₂ 是氢原子、羧基保护基团或药学上可接受的金属或有机阳离子； R₃和 R₄（可以相同或不同）是氢原子、低级烷基、酰基或可在体内代谢的氮保护基团； Z 是氢原子或卤素原子、氨基、羟基或甲基；以及 n 为 1 至 3。