1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo-7-(4-phenacyl-1-piperazinyl)-quinoline-3-carboxylic acid | 353793-88-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo-7-(4-phenacyl-1-piperazinyl)-quinoline-3-carboxylic acid
• 英文别名: 1-Ethyl-6,8-difluoro-4-oxo-7-(4-phenacylpiperazin-1-yl)quinoline-3-carboxylic acid
• CAS: 353793-88-1
• 化学式: C₂₄H₂₃F₂N₃O₄
• 分子量: 455.461
• InChiKey: GHBPWICREFXPCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 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：
  9

反应信息

• 作为反应物：
  描述：

  盐酸氨基脲 、 1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo-7-(4-phenacyl-1-piperazinyl)-quinoline-3-carboxylic acid 在 碳酸氢钠 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以71%的产率得到(Z)-1-ethyl-6,8-difluoro-4-oxo-7-[4-(2-phenyl-2-semicarbazonoethyl)piperazinyl]-1,4-dihydroquinone-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
• 作为产物：
  描述：

  1-乙基-4-氧代-6,8-二氟-7-哌嗪基-1,4-二氢喹啉-3-羧酸 、 2-溴苯乙酮 在 potassium iodide 、 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以73%的产率得到1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo-7-(4-phenacyl-1-piperazinyl)-quinoline-3-carboxylic acid
  参考文献：
  名称：

  6-fluoro-1,4-dihydro-7-[4-(2-hydroxyiminoethyl)-1-piperazinyl]-4-oxoquinoline-3-carboxylic acid derivatives, their preparation and pharmaceutical compositions

  摘要：

  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。

  公开号：

  US20020061895A1

文献信息

• 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-[4-(2-hydroxyiminoethyl)-1-piperazinyl]-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。
• QUINAZOLINE DERIVATIVES AND THEIR USE AS PHARMACEUTICALS
  申请人：AstraZeneca AB

  公开号：EP1218354A1

  公开（公告）日：2002-07-03
• US6492373B2
  申请人：——

  公开号：US6492373B2

  公开（公告）日：2002-12-10
• [EN] QUINAZOLINE DERIVATIVES AND THEIR USE AS PHARMACEUTICALS<br/>[FR] DERIVES DE QUINAZOLINE ET LEUR UTILISATION COMME PRODUITS PHARMACEUTIQUES
  申请人：ASTRAZENECA AB

  公开号：WO2001021596A1

  公开（公告）日：2001-03-29

  The use of a compound of formula (I) or a salt, ester, amide or prodrug thereof; where X is O, or S, S(O) or S(O)2, NH or NR12 where R12 is hydrogen or C¿1-6? alkyl; R?5¿ is selected from a group NHC(O)OR9, NHC(O)R9, NHS(O)¿2?R?9, C(O)R9¿, C(O)OR?9, S(O)R9¿, S(O)OR9, S(O)¿2OR?9, C(O)NR10 R11, S(O)NR10R11 S(O)ONR10R11, where R?9, R10 or R11¿ are various specified organic groups; R6 is hydrogen, optionally substituted hydrocarbyl or optionally substituted heterocyclyl; R?7 and R8¿ are various specified organic groups, and R?1, R2, R3, R4¿ are independently selected from halogeno, cyano, nitro, C¿1-3?alkylsulphanyl, -N(OH)R?13¿-(wherein R7 is hydrogen, or C¿1-3?alkyl), or R?15X1¿-(wherein X1 represents a direct bond, -O-, -CH¿2?-, -OCO-, carbonyl, -S-, -SO-, -SO2-, -NR?16¿CO-, -CONR16-, -SO¿2?NR?16-, -NR17SO¿2- or -NR18-(wherein R?16, R17 and R18¿ each independently represents hydrogen, C¿1-3?alkyl or C1-3alkoxy C2-3alkyl), and R?9¿ is hydrogen, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or optionally substituted alkoxy; in the preparation of a medicament for use in the inhibition of aurora 2 kinase.