ethyl 7-bromo-1-cyclopropyl-6,8-difluoro-4-quinolone-3-carboxylate | 123942-25-6

• 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: ethyl 7-bromo-1-cyclopropyl-6,8-difluoro-4-quinolone-3-carboxylate
• 英文别名: Ethyl 7-bromo-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate；Ethyl 7-bromo-1-cyclopropyl-6,8-difluoro-4-oxoquinoline-3-carboxylate
• CAS: 123942-25-6
• 化学式: C₁₅H₁₂BrF₂NO₃
• 分子量: 372.166
• InChiKey: XMAPELXNWCUMOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 7-bromo-1-cyclopropyl-6,8-difluoro-4-quinolone-3-carboxylate 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 作用下， 以 乙醇 为溶剂， 反应 23.0h， 生成 1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7-(3-pyridinyl)-3-quinolinecarboxylic acid
  参考文献：
  名称：

  Mammalian topoisomerase II inhibitory activity of 1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(2,6-dimethyl-4-pyridinyl)-4-oxo-3-quinolinecarboxylic acid and related derivatives

  摘要：

  1-Cyclopropyl-6,8-difluoro-1,4-dihydro-7-(2,6-dimethyl-4-pyridinyl)-4-oxo-3-quinolinecarboxylic acid (1), a previously reported potent inhibitor of bacterial DNA gyrase, was found to be interactive with mammalian topoisomerase II (topo II). In a DNA-cleavage assay using topo II isolated from HeLa cells, 1 exhibited an EC50 value of 7.6 muM (VP-16; EC50 = 0.81 muM). A series of analogues modified at the 1-, 2-, 3-, 5-, and 7-positions of 1 were subsequently made and assessed for topo II inhibition. Compound 1 was considerably more potent than derivatives where the 1-substituent was alkyl, aryl, or H, or when N-c-C3H5 was replaced with S. The descarboxyl (i.e., 3-H) analogue had potency comparable to that of 1; when both these compounds were substituted at the 2-position with methyl or phenyl, an interesting relationship between activity and the conformation of the carboxyl group emerged. Upon replacement of the 5-H of 1 with NH2 or F, sustained potency was seen. No enhancement of activity was evident upon replacing the 7-substituent of 1 with other pyridinyl groups, 4-methyl-1-piperazinyl, or pyrrolidinyl groups; however, the 7-(4-hydroxyphenyl) analogue (CP-115,953) was 6-fold more potent than 1. The topo II inhibitory properties of 1 translated to modest in vitro cytotoxicity and in vivo activity versus P388.

  DOI：

  10.1021/jm00071a010
• 作为产物：
  描述：

  diethyl 2-(N-(3-bromo-2,4-difluorophenyl)-(N-cyclopropylamino)methylene) malonate 在 polyphosphoric acid 作用下， 以 正己烷 为溶剂， 反应 3.5h， 以37%的产率得到ethyl 7-bromo-1-cyclopropyl-6,8-difluoro-4-quinolone-3-carboxylate
  参考文献：
  名称：

  通往关键中间体的简洁途径，可多样化合成C7取代的氟喹诺酮衍生物

  摘要：

  已经开发出一种简明的路线来制备7-溴-1-环丙基-6,8-二氟-4-喹诺酮-3-羧酸乙酯。该化合物是多种C7取代的氟喹诺酮类药物（多种有前景的临床应用的有效拓扑异构酶II抑制剂）的多样化合成的关键中间体。

  DOI：

  10.1016/j.tetlet.2009.11.077

文献信息

• Pyridinyl-quinolone compounds, their preparation and use
  申请人：Sterling Drug Inc.

  公开号：US05075319A1

  公开（公告）日：1991-12-24

  Fluorinated 1-cyclopropyl-7-(substituted-pyridinyl)-1,4-dihydro-4-oxo-3-quinolinecarbo xylic acids of the formula ##STR1## wherein R is hydrogen, R' and R" are hydrogen or fluoro, or other groups and Z is 3- or 4-pyridinyl substituted by alkyl groups or substituted alkyl groups, are superior antibacterial agents. They are prepared via a coupling reaction between the corresponding esters (R=alkyl) having a halo group in the 7-position and a substituted (trialkylstannyl)pyridine.

  氟化的1-环丙基-7-(取代吡啶基)-1,4-二氢-4-氧代-3-喹啉羧酸的化学式为##STR1##其中R为氢，R'和R"为氢或氟，或其他基团，Z为被烷基或取代烷基取代的3-或4-吡啶基，是优秀的抗菌剂。它们是通过对应酯（R=烷基）在7位具有卤素基团和取代（三烷基锡基）吡啶之间的偶联反应制备的。
• Quinoline and naphthyridine carboxylic acid antibacterials
  申请人：——

  公开号：US20020049223A1

  公开（公告）日：2002-04-25

  Compounds having formula (I) 1 or pharmaceutically acceptable salts or prodrugs thereof, are useful as antibacterial agents.

  具有化学式(I)1的化合物或其药用可接受的盐或前药，可用作抗菌剂。
• 4-Oxo-3-quinolinecarboxylic acids useful as antibacterial agents and preparation thereof
  申请人：STERLING WINTHROP INC.

  公开号：EP0309789A1

  公开（公告）日：1989-04-05

  A compound useful as an antibacterial agent having the formula: wherein: R is hydrogen or lower-alkyl; R′ is hydrogen, fluoro or -SR‴, where R‴ is phenyl, benzyl or lower-alkyl; R˝ is selected from hydrogen, fluoro and -SR‴, with the proviso that when R˝ is hydrogen, R′ is also hydrogen; or a pharmaceutically acceptable acid-addition salt thereof; or an alkali metal or amine salt of a compound where R is hydrogen as well as processes for the preparation thereof.

  一种可用作抗菌剂的化合物，其式如下 其中 R是氢或低级烷基； R′是氢、氟或-SR‴、 其中 R‴ 是苯基、苄基或低级烷基； R˝ 选自氢、氟和 -SR‴，但 R˝ 为氢时，R′ 也为氢； 或其药学上可接受的酸加成盐；或 R 为氢的化合物的碱金属盐或胺盐及其制备方法。
• US5075319A
  申请人：——

  公开号：US5075319A

  公开（公告）日：1991-12-24
• US5169853A
  申请人：——

  公开号：US5169853A

  公开（公告）日：1992-12-08