ethyl 4-bromo-2,3,5-trifluorobenzoylacetate | 122033-63-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 4-bromo-2,3,5-trifluorobenzoylacetate
• 英文别名: ethyl 3-(4-bromo-2,3,5-trifluorophenyl)-3-oxopropanoate
• CAS: 122033-63-0
• 化学式: C₁₁H₈BrF₃O₃
• 分子量: 325.082
• InChiKey: CUZSUTZUOARVCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 4-bromo-2,3,5-trifluorobenzoylacetate 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium hydride 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 18.0h， 生成 ethyl 6,8-difluoro-1,4-dihydro-7-(2,6-dimethyl-4-pyridinyl)-1-(1,1-dimethylethyl)-4-oxo-3-quinolinecarboxylate
  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：

  4-bromo-2,3,5-trifluorobenzoyl chloride 、 丙二酸单乙酯 、 正丁基锂 生成 ethyl 4-bromo-2,3,5-trifluorobenzoylacetate
  参考文献：
  名称：

  LESHER, GEORGE Y.

  摘要：

  DOI：

文献信息

• Tricyclic-pyridinylquinoline compounds, their preparation and use
  申请人：Sterling Drug Inc.

  公开号：US04839355A1

  公开（公告）日：1989-06-13

  Fluorinated 10-(2,6-dimethyl-4-pyridinyl)-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-d e][1,4]benzoxazine-6-carboxylic acids and -benzothiazine-6-carboxylic acids of the formula ##STR1## wherein R is hydrogen, R' is hydrogen or fluoro, R" is alkyl of 1-3 carbon atoms and X is O or S are superior antibacterial agents.

  氟化的式为##STR1##的10-(2,6-二甲基-4-吡啶基)-3-甲基-7-氧代-2,3-二氢-7H-吡啶[1,2,3-d e][1,4]苯并噁唑-6-羧酸和-苯并噻唑-6-羧酸，其中R为氢，R'为氢或氟，R"为1-3个碳原子的烷基，X为O或S，是优越的抗菌剂。
• 4-Oxo-3-Quinolinecarboxylic acids useful as antibacterial agents and preparation thereof
  申请人：STERLING WINTHROP INC.

  公开号：EP0306860A2

  公开（公告）日：1989-03-15

  A compound useful as an antibacterial agent compound having the formula: wherein: R is hydrogen or lower alkyl; R′ is hydrogen, fluoro or -SR‴, where R‴ is benzyl, phenyl or lower-alkyl; R˝ is alkyl of 1-3 carbon atoms; X is O or S; 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‴ 是苄基、苯基或低级烷基； R˝ 是 1-3 个碳原子的烷基； X 是 O 或 S； 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工艺。
• LESHER, GEORGE Y.
  作者：LESHER, GEORGE Y.

  DOI：——

  日期：——
• US4839355A
  申请人：——

  公开号：US4839355A

  公开（公告）日：1989-06-13
• [EN] STIMULATOR OF INTERFERON GENES (STING) MODULATORS, AND COMPOSITIONS AND METHODS THEREOF<br/>[FR] MODULATEURS DE STIMULATEUR DE GÈNES D'INTERFÉRON (STING), ET COMPOSITIONS ET MÉTHODES ASSOCIÉES
  申请人：[en]GEODE THERAPEUTICS INC.

  公开号：WO2023158862A2

  公开（公告）日：2023-08-24

  The invention provides novel modulators of STING (Stimulator of Interferon Genes) and pharmaceutical compositions thereof, as well as methods of their preparation and use, in therapy of various diseases and conditions, such as cancer, infectious and autoimmune diseases or disorders.