1-ethyl-6-fluoro-7-{4-[2-(4-chlorophenyl)-2-oxoethyl]-1-piperazinyl}-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 307543-29-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-ethyl-6-fluoro-7-{4-[2-(4-chlorophenyl)-2-oxoethyl]-1-piperazinyl}-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 7-{4-[2-(4-chlorophenyl)-2-oxoethyl]-1-piperazinyl}-1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid；1-ethyl-6-fluoro-7-{4-[2-(4-chlorophenyl)-2-oxoethyl]-1-piperazinyl}-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid；7-[4-[2-(4-Chlorophenyl)-2-oxo-ethyl]piperazin-1-yl]-1-ethyl-6-fluoro-4-oxo-quinoline-3-carboxylic acid；7-[4-[2-(4-chlorophenyl)-2-oxoethyl]piperazin-1-yl]-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 307543-29-9
• 化学式: C₂₄H₂₃ClFN₃O₄
• 分子量: 471.916
• InChiKey: IHUXNXVIPZKNNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  81.2
• 氢给体数：
  1
• 氢受体数：
  8

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  诺氟沙星	1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid	70458-96-7	C16H18FN3O3	319.336

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	1-Ethyl-6-fluoro-7-{4-[2-(4-chlorophenyl)-2-hydroxyimino-ethyl]-1-piperazinyl}-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid	——	C24H24ClFN4O4	486.93
  ——	1-ethyl-6-fluoro-7-{4-[2-(4-chlorophenyl)-2-methoxyiminoethyl]-1-piperazinyl}-4-oxo-1,4-dihydroquinoline-3-carboxylic acid	——	C25H26ClFN4O4	500.957

反应信息

• 作为反应物：
  描述：

  1-ethyl-6-fluoro-7-{4-[2-(4-chlorophenyl)-2-oxoethyl]-1-piperazinyl}-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 、 2-溴甲基丙烯酸乙酯 在 对苯二酚 、 锌 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 以91%的产率得到7-{4-{[2-(4-chlorophenyl)-2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl]methyl}piperazin-1-yl}-1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and Cytotoxic Activities ofα-Methylidene-γ-butyrolactones Bearing a Quinolin-4(1H)-one Moiety

  摘要：

  The cytotoxicities of the u-methylidene-gamma -butyrolactones 4. 5. and 8. which are linked to a quinolin-4(1H)-one moiety through a piperazine or O-atom bridge were studied. These compounds were synthesized by alkylation of 1-ethyl-6-fluoro-1,4-dihydro-7-hydroxy-4-oxoquinoline-3-carboxylic acid (6) followed by a Reformatsky-type condensation. Compounds 4. 5. and 8 were evaluated in vitro against 60 human-tumor cell lines derived from nine cancer-cell types and demonstrated not only strong growth-inhibitory activities against leukemia cancer cells. but also fairly good activities against the growth of certain solid tumors (see Table). The O-bridged derivatives 8a and 8b exhibit both cytostatic (mean log GI(50) = -5.20 and - 5.82, resp.) and cytocidal (mean log LC50 = - 4.30 and -4.93. resp.) effects, while the piperazine-bridged analogues 4 and 5 possess only weak cytostatic (mean log GI(50) = - 5.20 and -5.82, resp. mean log LC50 > -4.00) capability, among them. 8b is the most potent, with log GI(50) = -6.47. -6.72. -653, and 6.52 against leukemia. SW-620 (colon). Lox IMVI, and SK-MEL-28 (melanoma) cancer cells. respectively.

  DOI：

  10.1002/1522-2675(20010418)84:4<874::aid-hlca874>3.0.co;2-i
• 作为产物：
  描述：

  诺氟沙星 、 2'-溴-4-氯苯乙酮 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-ethyl-6-fluoro-7-{4-[2-(4-chlorophenyl)-2-oxoethyl]-1-piperazinyl}-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and Antibacterial Evaluation of Certain Quinolone Derivatives

  摘要：

  A number of 7-substituted quinolone derivatives were synthesized and evaluated for antibacterial and cytotoxic activities. Preliminary results indicated that most compounds tested in this study demonstrated better activity against methicillin-resistant Staphylococcus aureus than norfloxacin. Among them, 1-(4-amino-2-fluorophenyl)-6-fluoro-1,4-dihydro-7-{4-[2-(4-methoxyphenyl)-2-hydroxyiminoethyl]-1-piperazinyl}-4-oxo-3-quinolinecarboxylic acid (11d) and its ketone precursor 10d exhibited significant activities against Klebsiella pneumoniae, methicillin-resistant S. aureus, erythromycin- and ampicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus faecalis. Due to strong cytotoxicities of lid (a mean log GI(50) of -5.40), compound 10d, with good antibacterial activities and low cytotoxicities (a mean log GI(50) of -4.67), is a more potential drug candidate.

  DOI：

  10.1021/jm0100335

文献信息

• 6-fluoro-1,4-dihydro-7-[4-(2-hydroxyiminoethyl)-1-piperazinyl]-4-oxoquinoline-3-carboxylic acid derivatives, their preparation and pharmaceutical compositions
  申请人：Pharmaceutical Industry Technology

  公开号：US20020061895A1

  公开（公告）日：2002-05-23

  The present invention discloses a novel 6-fluoro-1,4-dihydro-7-[4-(2-hydroxyiminoethyl)-1-piperazinyl]-4-oxoquinoline-3-carboxylic acid derivatives (formula I), with a process for their preparation, and with pharmaceutical compositions containing them as the active ingredient for the treatment of bacterial infections and/or renal cancer diseases. 1

  本发明揭示了一种新颖的6-氟-1,4-二氢-7-[4-(2-羟基亚胺基乙基)-1-哌嗪基]-4-氧喹啉-3-羧酸衍生物（式I），以及它们的制备方法和含有它们作为活性成分的药物组合物，用于治疗细菌感染和/或肾癌疾病。
• Synthesis, and Antimycobacterial and Cytotoxic Evaluation of Certain Fluoroquinolone Derivatives
  作者：Jia-Yuh Sheu、Yeh-Long Chen、Cherng-Chyi Tzeng、Shu-Lin Hsu、Kuo-Chang Fang、Tai-Chi Wang

  DOI：10.1002/hlca.200390201

  日期：2003.7

  Certain 1-ethyl- and 1-aryl-6-fluoro-1,4-dihydroquinol-4-one derivatives were synthesized and evaluated for antimycobacterial and cytotoxic activities. Preliminary results indicated that, for 1-aryl-6-fluoroquinolones, both 7-(piperazin-1-yl)- and 7-(4-methylpiperazin-1-yl) derivatives, 9b and 11a, are able to completely inhibit the growth of M. tuberculosis at a concentration of 6.25 μg/ml, while

  合成了某些1-乙基和1-芳基-6-氟-1,4-二氢喹啉-4-酮衍生物，并评估了其抗分枝杆菌和细胞毒性的活性。初步结果表明，对于1-芳基-6-氟喹诺酮类化合物，7-（哌嗪-1-基）-和7-（4-甲基哌嗪-1-基）衍生物9b和11a均能够完全抑制生长。的结核分枝杆菌在6.25微克/ ml的浓度，而7- [4-（2-氧代-2-苯乙基）哌嗪-1-基]衍生物13所仅表现出31％的生长抑制在相同的浓度。对于1-乙基-6-氟喹诺酮类化合物，7- [4-（2-氧代丙基）哌嗪-1-基]-和7- [4-（2-氧代-2-苯基乙基）哌嗪-1-基]衍生物，2a和2b分别显示出完全的抑制作用，而它们的2-亚氨基乙基和取代的苯基对应物3a和2c的活性较低。另外，6,8-二氟衍生物比其6-氟衍生物（2b vs. 2d）是更有利的抑制剂。这些结果值得特别关注，因为2a，2b，9b和11a在100μM的浓度下无细胞毒性。此外
• 6-fluoro-1,4-dihydro-7-&lsqb;4-(2-hydroxyiminoethyl)-1-piperazinyl&rsqb;-4-oxoquinoline-3-carboxylic acid derivatives, their preparation and pharmaceutical compositions
  申请人：Pharmaceutical Industry Technology and Development Center

  公开号：US06492373B2

  公开（公告）日：2002-12-10

  The present invention discloses a novel 6-fluoro-1,4-dihydro-7-[4-(2-hydroxyiminoethyl)-1-piperazinyl]-4-oxoquinoline-3-carboxylic acid derivatives (formula I), with a process for their preparation, and with pharmaceutical compositions containing them as the active ingredient for the treatment of bacterial infections and/or renal cancer diseases.

  本发明揭示了一种新型的6-氟-1,4-二氢-7-[4-(2-羟基亚胺乙基)-1-哌嗪基]-4-氧代喹啉-3-羧酸衍生物（式I），其制备过程以及含有它们作为活性成分的药物组合物，用于治疗细菌感染和/或肾癌疾病。
• Synthesis, Antibacterial, and Cytotoxic Evaluation of Certain 7-Substituted Norfloxacin Derivatives
  作者：Kuo-Chang Fang、Yeh-Long Chen、Jia-Yuh Sheu、Tai-Chi Wang、Cherng-Chyi Tzeng

  DOI：10.1021/jm000153x

  日期：2000.10.1

  We report herein the synthesis and biological evaluation of two series of 7-substituted norfloxacin derivatives. Most compounds tested in this study demonstrated better activity against methicillin-resistant Staphylococcus aureus than norfloxacin. Preliminary in vitro evaluation indicated that the 7-[4-(2-hydroxyiminoethyl)piperazin-1-yl] derivatives 3b-e possess distinct cytotoxicity profiles as compared with their alpha-methylene-gamma-butyrolactone counterparts, 4b,e: i.e., excellent activities against the renal cancer subpanel. Among them, 1-ethyl-6-fluoro-7-4-[2-(4-chlorophenyl)-2-hydroxyiminoethyl]-1-piperazinyl}-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (3d) demonstrated the most significant activities against renal cancer cell lines, with log GI(50) values of -6.40 against CAK-1, -6.14 against RXF 393, and -7.54 against UO-31, compared with a mean log GI(50) value of -5.03.
• US6492373B2
  申请人：——

  公开号：US6492373B2

  公开（公告）日：2002-12-10